Myths on Myths about stem cells

There's a new Public Broadcasting System (your tax dollars at work) television show on "stem cells," "Mapping Stem Cell Research: Terra Incognita."

You don't have to go any farther than the top of the home page, with its picture of a girl in a wheelchair and this quote,

"Some people consider stem cell biology to be the Holy Grail of Regenerative Medicine, while others view embryonic stem cell use as morally wrong."

to see that it's propaganda for embryonic stem cell research and cloning for embryonic stem cells. The authors immediately begin the pattern of using the term "stem cells" for both of the two basic kinds of stem cells: those that require the destruction of a human life and those that don't.

Here are the first three points from the "Myths and Realities" page, with my comments in Bold after each.

MYTH
Stem cell research uses aborted fetuses.
REALITY
Stem cells can be totipotent (a fertilized egg with the “total potential” to give rise to all different types of cells in the body), multipotent (stem cells that can give rise to a small number of different cell types), or pluripotent (stem cells that can give rise to any type of cells in the body except those that are needed to develop a fetus). While pluripotent stem cells could be developed from fetal tissue or even adults, they are best derived from early-stage embryos, a mass of cells that is only a few days old—not aborted fetuses.

The authors skip over the significance of the fact that embryronic stem cells come from destroyed human embryos in the lab, it is true that most stem cell research does not use tissues obtained from abortions. Nowadays, however, the term "fetus" is too often used by the media (and even researchers who ought to know better) for all pre-born human beings. The proper definition of human embryo is the organism from fertilization or the beginning of the first cell division to 7-8 weeks of age. The term "fetus" in humans is properly used from 8 weeks until birth.

More on the claims about what is the "best" source of stem cells and about "embryonic-like stem cells," below.

MYTH
Somatic cell nuclear transfer using human cells involves the use of fertilized eggs.
REALITY
Somatic cell nuclear transfer, the process in which the nucleus from an adult cell is removed and then transferred to an egg whose nucleus has been removed, is the first step in cloning and can be used to create an embryonic stem cell line. However, an egg cell does not need to be fertilized to be used in this procedure—an unfertilized egg cell can be used.

Here, the authors avoid using "embryo" and throw around the terms "unfertilized egg" and "fertilized egg." An embryo is not a "fertilized egg" - once an egg is fertilized, it becomes an embryo. In Somatic Cell Nuclear Transfer (cloning), the embryo is produced artificially by inserting the DNA of a donor cell and stimulating division and organized development that occurs with natural reproduction. When human DNA is used to produce human embryonic cells in an organized embryo, there can be no doubt that what we are talking about is a human embryo. No matter how he or she is created - or produced - or how severely handicapped by the intentions and actions of the producers, a human embryo is a very young human being.

MYTH
Researchers can use adult stem cells instead of embryonic stem cells. Other treatments using adult stem cells are available to treat conditions such as Parkinson's disease and spinal cord injuries.
REALITY
Adult stem cells lack the versatility and flexibility of embryonic stem cells, making them less likely to lead to medical breakthroughs. Embryonic stem cells have a far greater developmental potential and are more likely to be pluripotent, while adult stem cells are thought to be merely multipotent, or restricted to only certain cell types.

In November 2007, Japanese and American research teams reported new ways to obtain stem cells that behaved like embryonic stem cells from human skin cells—without having to use human embryos. This breakthrough holds great promise in solving the ethical dilemmas of stem cell research, but scientists currently still face technical hurdles and the challenge of finding ways to use these stem cells successfully in medical treatments and therapies.

The biggest lie of all is that embryonic stem cells are more useful in treatments for human beings. Just ask the 20,000 plus in the US alone who have been treated with adult and umbilical cord stem cells or go looking for even one human who has been treated with embryonic stem cells.

While it is true that most ethical, adult stem cells are not "pluripotent," there are many kinds of "multipotent" stem cells and precursor cells in the body. In fact, these are the cells that we probably will use in the future, because they are the cells the body uses to repair itself and because they are less likely to grow out of control or cause tumors.

We are also learning that the desired development of stem cells and precursor cells is influenced by the environment and all sorts of "factors," or chemical and physical signals present in the part of the body where they grow into cells, tissues and organs. The key to future treatment for most disease will probably come from learning to stimulate these conditions and factors.

Besides the ethical dilemma of destroying early human life, embryonic stem cell research has every problem or hurdle that could be cited for adult stem cells: they are difficult to grow, found in small numbers, the cultures may be contaminated with different, undesirable cell lines, and are difficult to control to produce for the exact stem cell line that is needed.

Moreover, no one wants to transplant embryonic stem cells into people. What we want is to produce adult stem cells for treatments.

The last paragraph mentions embryonic-like stem cells. There are several ways to produce stem cells that behave in every way that the unethical stem cells do.

These cells are being used in research to replace the unethical cells produced by destruction of embryos.

The goal of all stem cell research is to have a source of "patient-specific" stem cells from the patient or to find ways to stimulate stem cell production in the body of the patient, when and where they are needed.

The producers of this program are advocating for outdated research methods.While researchers have learned a lot from human embryo research in the past, most of what we use has been developed from research in animal models. The production of new embryonic stem cell lines from human embryos and from cloning is no longer necessary to carry out this research.


(Thanks to Janet, of the Bedford County Citizens Concerned for Human Life, for sending me the link to the website on the show.)

Wash this reactionary's mouth out with soap!

Bioethics.net compares the Bush administration's happiness about reprogrammed adult stem cells with that man, Mr. Clinton's, "I did not have sex with that woman!" and President Bush's statement "Mission accomplished," after our US troops captured Baghdad.

I'll accept the latter (at some future date, if the evidence supports it), but the first is at least as false as Clinton's wagging finger - and (speaking of Yuk factors) did we really need to be reminded of that?

The author, James W. Fossett (who is anything but "non-partisan") states that Yamanaka, the first to report reprogrammed adult cells in humans and mice is from Japan and wasn't affected by the US Federal funding limitations. He doesn't mention that Yamanaka's research didn't rely on the use of new embryonic cells, at all. Yamanaka took the information gleaned from animal research and the currently funded cells and moved to the front of all other stem cell researchers by pointing the way to the key to the production of stem cells from each patient who needs them - from his or her own cells.

Instead, Fossett is running scared due to the "rhetorical parity" from cell reprogramming and the possibility that the success in reprogramming cells will result in more reprogramming research!

Fossett doesn't mention that James Thomson's research using human Embryonic Stem cells (hESC). then human fetal cells harvested after abortions - and finally in skin cells harvested at circumcision of little boys - was funded by the National Institutes of Health, and that those hESC are the ones that supposedly are of no use.

Fossett also fails to mention of the new report by Yamanaka on the technique using only 3 inserted genes to the prior 4, and that the eliminated gene is the one that had scientists concerned about cancers.

I'm sure that he doesn't recall the "first transplantable lung cells" from hESC's by Texas researchers last year. These cells were developed by viral "transfection," also, and were lauded as "a platform that could potentially be useful in the development of spinal cord cells, heart cells, nerve cells and others.” These were neither the first or transplantable, but they did get much more notice than similar cells developed from umbilical cord blood cells without viral transfection.

That may be the problem: the proponents of hESC research are used to getting many times the publicity from hESC research than that received by the non-hESC researchers. And so, we get the concerns about "rhetoric."

There's those deceitful knee jerk reactionaries practicing their projection, again.

More Questions on Embryonic Stem Cells

Lydia asked about my comments on embryonic-like cells derived from umbilical cord blood.

Umbilical cord blood itself appears to be at least multipotent. However, Texan and British researchers worked with NASA to produce "embryonic-like" stem cells by manipulating them with filters and a special centrifuge. Here's my post from August, 2005 on those cells.

And here's the press release from McGuckin's university in the UK.

And here's the abstract from the Journal, Cell Proliferation,

"Production of stem cells with embryonic characteristics from human umbilical cord blood"

C. P. McGuckin, N. Forraz, M.-O. Baradez, S. Navran, Synthecon Corporation, Houston, and J. Zhao, R. Urban, Tilton, L. Denner

When will embryonic stem cells reach the clinic? The answer is simple – not soon! To produce large quantities of homogeneous tissue for transplantation, without feeder layers, and with the appropriate recipient's immunological phenotype, is a significant scientific hindrance, although adult stem (ADS) cells provide an alternative, more ethically acceptable, source. The annual global 100 million human birth rate proposes umbilical cord blood (UCB) as the largest untouched stem cell source, with advantages of naive immune status and relatively unshortened telomere length. Here, we report the world's first reproducible production of cells expressing embryonic stem cell markers, – cord-blood-derived embryonic-like stem cells (CBEs). UCB, after elective birth by Caesarean section, has been separated by sequential immunomagnetic removal of nucleate granulocytes, erythrocytes and haemopoietic myeloid/lymphoid progenitors. After 7 days of high density culture in microflasks, (105 cells/ml, IMDM, FCS 10%, thrombopoietin 10 ng/ml, flt3-ligand 50 ng/ml, c-kit ligand 20 ng/ml). CBE colonies formed adherent to the substrata; these were maintained for 6 weeks, then were subcultured and continued for a minimum 13 weeks. CBEs were positive for TRA-1-60, TRA-1-81, SSEA-4, SSEA-3 and Oct-4, but not SSEA-1, indicative of restriction in the human stem cell compartment. The CBEs were also microgravity–bioreactor cultured with hepatocyte growth medium (IMDM, FCS 10%, HGF 20 ng/ml, bFGF 10 ng/ml, EGF 10 ng/ml, c-kit ligand 10 ng/ml). After 4 weeks the cells were found to express characteristic hepatic markers, cytokeratin-18, α-foetoprotein and albumin. Thus, such CBEs are a viable human alternative from embryonic stem cells for stem cell research, without ethical constraint and with potential for clinical applications.

These cells were later used to produce functional liver tissue and alveolar lung cells.

There have also been bone marrow cells that share the characteristic markers of embryonic stem cells. (Reported here.)

"George Bush and the Catholic Church hold us in thrall"

That's what Terry over at the Womens Bioethics Project Blog says. Terry has a big problem with the breakthrough in stem cell research that so many of us are thrilled with, and says,

It is amazing to see how the Catholic Church and George Bush can hold us all in thrall regarding human embryonic stem cell research. Because of the opposition to deriving stem cells from human embryos which destroys the embryo, eminent scientists are now reduced to attempting to find stem cell alternatives and have done so - by creating induced pluripotent stem cell lines derived from human somatic cells, an advance (?) which is being heralded today in the NY Times. In other words, we can regress human skin cells to an embryonic state by introducing retroviruses including c-Myc (cancer cells) to do so. The only problem with this is that it also creates tertomas which are nasty little creatures - effectively a germ cell tumor which may contain hair, teeth, bones, eyeballs, torsos and hands. Yuk, as Leon Kass would say. Here's an idea: instead of trying to create human embryonic stem cells from someone's nose or foreskin, let us do the research on embryos as nature intended.

Really Terry? "As nature intended?"" Nature intended for us to "use the original container," when it came to embryos.


Most of the basic research was done in mice - look at the history of Yamanaka & Takahashi's research, along with the reports published by Jaenisch this summer.

And Terry's way off on the teratomasas draw back: the *ability* to form teratomas in immune-deficient mice is one of the tests necessary if a researcher wants to prove that the cells are embryonic-like or pluripotent stem cells. (As opposed to multipotent - the fact that his cells did not make teratomas was one criticism of Atala's amniotic stem cell work. Gearhart was specific about the pressure he and others placed on Atala, so I expect to hear more about that in the future.)

Embryonic stem cells have always had all the problems that Terry mentions - including the retrovirus manipulation in many cases, look up "first transplantable lung cells" from the Houston, Texas Stem cell researchers here and here - in addition to the ethical problem of requiring the destruction of human embryos and the necessity to consider buying or bartering for oocytes.

Embryonic stem cells have the same concerns about the ability to reliably direct the cells toward the desired cell line, about the lack of regulation inherent in the primitive cells in culture, and ensuring that a more primitive cell - a future tumor - was not transplanted with the derived, less plastic cells.

One huge advantage that the new process offers that has never been achieved before, is the ability to make patient specific cells for everyone, not just the elite few who can afford to buy the oocytes.

The viruses used are strongly "silenced" or suppressed in the culture conditions used to direct development and are well known - the research to remove them from the DNA is not predicted to be all that hard. But that shouldn't really be a problem form long: between the two researchers and the information coming out of other labs, I wouldn't be surprised if we are able to skip the transfection in a year or two.

In the meantime, Wilmut has announced that the science is driving him to abandon embryonic research and cloning (especially using animal oocytes and human nuclear DNA to form a cimera), Yamanaka and Thomson are getting ready to patent and sell their cell lines for drug research and basic science, as well as anticipating future transplants.

Bioethics on the Ballot

Texas approved Billions in bond debt, some $3 Billion of which will fund the new Cancer Prevention and Research Institute of Texas. There is already private funding of embryonic and fetal tissue research in Texas already.(See this report on the Brown Institute in Houston.) While Texas is a leader in ethical stem cell research and public cord blood banking, there are no limits on State tax funds for research that would limit any sort of destructive research on unborn humans, including cloning, embryonic stem cell research and fetal research. As long as none of the subjects are able to hire a lawyer, it's open season in Texas. The prolife community in Texas is hoping - and has already begun the fight - to ensure that the oversight board will be able to control the use of the money for ethical means.

New Jersey, on the other hand, rejected funding for embryonic stem cells! Hooray!

Small Town Hospital Collects Cord Blood for Texas Public Banks

I was so happy to hear that my local hospital is now one of the hospitals that collects cord blood for the public banks.

The cells from cord blood are rich in adult stem cells that can be used to replace the bone marrow of children with blood disorders and for treatment of all sorts of diseases. How about that: a small hospital in a small town can join in adult stem cell therapy!

See my grand daughter's story, here.

Type I diabetes and cord blood

Researchers at the University of Florida have treated children, aged 2 to 7, with infusions of their own stored cord blood, with some improvement in insulin production and control of blood sugar.

No one knows the exact mechanism that causes the disease we know as Juvenile or Type I Diabetes Melitus (DMI), but it is thought to be due to some combination of auto-immune disease (when the body's immune system causes damage to its own tissues) and possibly an infection, along with an unknown genetic susceptibility. Not only do the patients make antibodies against their own insulin-producing cells, they also make antibodies against their own insulin. It appears that the cord blood contains regulatory T cells which reverse some of the effects of the DMI on the pancreas.

From the University of Florida press release:

UF researchers identified children recently diagnosed with type 1 diabetes whose families banked their
umbilical cord blood at birth. Most were still producing a small amount of insulin. The researchers then gave seven patients ages 2 to 7 intravenous infusions of stem cells isolated from their own cord blood. (They have since treated an additional four children.) The patients were evaluated for the next two years to measure how much insulin they were making on their own and to assess blood sugar levels and the function of key immune system cells.

In the first six months, they required significantly less insulin — on average 0.45 versus 0.69 units of insulin per kilogram per day — and maintained better control of blood sugar levels than children of comparable age with type 1 diabetes who were randomly selected from the clinic population. The researchers also noted that the children who received cord blood infusions had higher levels of regulatory immune cells in their blood six months after the infusion, on average 9 percent of the total cell volume compared with 7.21 percent at the time of infusion.

“This isn’t a cure-all. We think that giving these cells is essentially providing some immunotherapy and downregulating the autoimmunity these patients have,” Haller said. “Realistically, we hope to protect what’s left of their insulin-production for an extended period of time. We think the immune regulation hypothesis is more likely than the hypothesis that stem cells are forming insulin producing cells on their own.”

The idea would be to intervene and repair any early damage during the “honeymoon period” many patients enjoy — the first several months after diagnosis during which insulin needs are minimal, he added.

The results are consistent with what we already know about Type I diabetes (DMI) and the stem cells that some receive from their mothers before or at birth. The men and women who were found to have functional stem cells from their mothers did not have complete remission of their DMI, either.

Hiatus (Over, I hope)

I haven't been blogging - I've been lobbying and working, instead. Whether in Austin or at work, my access to the blog is spotty. And I worried that anything I wrote might get in the way of some bills we were fighting for.

Unfortunately, the Texas legislature is self-destructing and virtually none of the pro-life, pro-family bills made it through.

One of the bills I was lobbying for contained amendments to the Texas Advance Directive Act (TADA) that would have increased protection for patients, prevented the removal of artificial hydration and nutrition, and more than doubled the time that doctors had to give medical treatment that they and others deemed "inappropriate." An improved process for communicating with families and a liaison between the family and the doctor was in the bill, which would have also added funding for facilities that offered complex medical treatments, such as dialysis for comatose patients, which simply don't exist in Texas. For two more years, we have the same law and the same arguments.

I do expect some of the recommendations, such as a dedicated liaison and improved communications to be adopted voluntarily in hospitals, as the good ideas that they are.

The Bill to limit embryonic stem cell research also failed, but we did get a brochure to explain the options available for donating cord blood and held the line on expanding unethical research, since several "clone and kill" bills were blocked.

Billions and Billions of stem cells (or ACT kills more mice needlessly)

Once again, ACT is hyping research that duplicates work already done using non-embryonic stem cell research. The only thing new is the possibility that they have come up with a way to make "Billions" of the plastic cells.

Ok, maybe we learned something from Advanced Cell Technology's Robert Lanza's latest human embryonic stem cell report published on line (free) prior to print in Nature Methods, "Generation of functional hemangioblasts from human embryonic stem cells." Perhaps the method of growing the cells without animal or human serum will prove useful.

This time, ACT is hyping their development of "hemangioblasts," the stem cells that become blood cells and the cells that make up the blood vessels, and the big claim is that the researchers at Advanced Cell Technology have a technique for making "billions and billions" of cells. Their own introduction explains that the group has not developed a new line of cells or proven anything new as far as vascular repair goes:

Although progenitor cells have recently been discovered that can enter the circulation in response to vascular injury and ischemia (1–5), defining and isolating these cells has proven problematic. Circulating bone marrow–derived cells have also been shown to be important in normal physiologic maintenance and repair of the body’s vasculature (6,7) with approximately 1–3% of endothelial cells at any one time being bone marrow–derived. Furthermore, the entire hematopoietic system has been hypothesized to originate from a transient population of hemangioblasts restricted to embryogenesis (8,9). But recent evidence suggests that hemangioblasts or more mature endothelial progenitors may also exist in adult tissues and umbilical cord blood (2–4,10,11).More direct proof for their existence was provided when the in vitro equivalent of the hemangioblast was isolated using a mouse embryonic stem cell differentiation system (12,13). Recently a human hemangioblast cell population derived from hES cells was also identified using a procedure that consisted of serum-free differentiation in a mixture of cytokines followed by expansion in serum-containing medium (14). To date, large-scale generation or functional assessment of hemangioblasts has not been achieved in any of these systems. Here we show that large numbers of what appear to be a distinct population of progenitor cells with both hematopoietic and vascular potential can be efficiently and reproducibly generated from hES cells using a simple two-step procedure with different supplements under fully serum-free conditions.

Here's those references, please note the titles:

1. Rafii, S. & Lyden, D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat. Med. 9, 702–712 (2003).
2. Grant, M.B. et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal eovascularization. Nat. Med. 8, 607–612 (2002).
3. Bailey, A.S. et al. Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells. Blood 103, 13–19 (2004).
4. Cogle, C.R. et al. Adult human hematopoietic cells provide functional hemangioblast activity. Blood 103, 133–135 (2004).
5. Otani, A. et al. Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat. Med. 8, 1004–1010 (2002).
6. Crosby, J.R. et al. Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. Circ. Res. 87, 728–730 (2000).
7. Hill, J.M. et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N. Engl. J. Med. 348, 593–600 (2003).
8. Wagner, R.C. Endothelial cell embryology and growth. Adv. Microcirc. 9, 45–75 (1980).
9. Park, C., Ma, Y.D. & Choi, K. Evidence for the hemangioblast. Exp. Hematol. 33, 965–970 (2005).
10. Loges, S. et al. Identification of the adult human hemangioblast. Stem Cells Dev. 13, 229–242 (2004).
11. Pelosi, E. et al. Identification of the hemangioblast in postnatal life. Blood 100, 3203–3208 (2002).
12. Choi, K., Kennedy, M., Kazarov, A., Papadimitriou, J.C. & Keller, G. A common precursor for hematopoietic and endothelial cells. Development 125, 725–732 (1998).
13. Kennedy, M. et al. A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 386, 488–493 (1997).
(Emphasis is mine)

As I said, the main claim in the article is that the ACT researchers made a large number of hemangioblasts, and set about proving that they were, indeed, hemangioblasts, through experiments on mice, which all had induced injuries and which were sacrificed for autopsy.

However, what do we read in the tabloids science mags?

From Scientific American.
"New Recipe for Powerful Stem Cells Promises Greater Insight."

Other groups had discovered hemangioblasts in mouse and human embryonic cells as well as in adult human bone marrow and umbilical cord blood. But they were unable to harvest them in large enough numbers to evaluate the cells' healing properties.

And from Technology Review, "Stem Cells Repair Blood Vessels: A new method to boost growth of blood vessels with stem cells could improve cell therapies for diabetes and heart disease."

And last, but not least, from Reuters, UK, "Embryonic stem cells can repair eyes, company says."

"For example, we injected the cells into mice with damaged retinas due to diabetes or other eye injury. The cells (labeled green) migrated to the injured eye, and incorporated and lit-up the entire damaged vasculature. The cells are really smart, and amazingly, knew not to do anything in uninjured eyes."

The researchers killed the mice to check the cells' progress, so they do not know the long-term effects.

What none of the articles mention is the ongoing studies using non-embryonic stem cells to do what ACT claims its embryonic stem cells will do.

There was this report in the American Journal of Pathology in 2006 and this one from 2004, published in the Journal of Clinical Investigation about using a patient's own bone marrow cells to repair eye injury. Both used mouse models.

There is also the Austin, Texas trial that I reported on last week, which is using donor bone marrow cells. And there are several studies, including one using the patient's own stem cells to treat "Critical Ischemic Limb," at Houston, Texas' Stem Cell Center at St. Luke's Hospital.

It appears that this is just one more example of hype and hope about cells that have already been studied - and even used in humans - when someone (ACT, too often) claims to have a new study proving that they have generated human embryonic stem cells of some sort or other and to have "cured" some disease. (in mice, if at all.)

"Sneaky" Texas Legislator

Perhaps this article, written by an Associated Press writer, should be receive the Yellow Brick Award. (Should I put "copyrighted" here? No, there's others, although most - like the award for finishing the obstacle course at Quantico - are awards for achieving the impossible, not for misdirection.)

Someone is practicing distraction and projection by calling a vote in the Texas House State Affairs Committee a "Sneak attack."

Friday's vote came after a committee meeting that began Thursday and lasted through the night. Critics said the vote came hours after testimony concluded and while the committee was focused on an unrelated bill.

"Those of us who rely on the hope stem cell research holds, and anyone who cares about an open public dialogue, should be outraged at the manner in which the vote was taken on Friday afternoon — without discussion and while two members opposed to the bill were absent," said Judy Haley, president of Texans for the Advancement of Medical Research.

Kathy Miller, president of the Texas Freedom Network, called the vote's timing a "sneak attack."

"It's a shameful case of putting politics ahead of science as well as patients and their families," she said.

The bill, HB 225 by Ken Paxton (R - District 70, McKinney)reads as follows:

By: Paxton, Olivo, Christian, Chisum, Parker, H.B. No. 225 et al.

A BILL TO BE ENTITLED AN ACT
relating to prohibiting the use of state money for certain
biomedical research.
BE IT ENACTED BY THE LEGISLATURE OF THE STATE OF TEXAS:
SECTION 1. Subtitle H, Title 2, Health and Safety Code, is amended by adding Chapter 169 to read as follows:

CHAPTER 169. BIOMEDICAL RESEARCH
Sec. 169.001. PROHIBITION ON USE OF STATE MONEY FOR CERTAIN BIOMEDICAL RESEARCH. A person may not use state money for biomedical research if federal law prohibits the use of federal money for that research on January 1, 2007.
SECTION 2. This Act takes effect September 1, 2007.

For those of us who object to embryonic stem cell research, the bill serves the purpose of preventing our tax dollars from being used to destroy embryos whether from existing in vitro embryos or from purposeful creation of new embryos for the purpose of research, including cloning or parthenogenesis.

And for the fiscally responsible, the bill ensures that any research we pay for will be eligible for additional Federal research funds, and/or we won't spend money on redundant labs and equipment.

The House was in session until nearly midnight last Thursday, and began hearing testimony on HB 225 about 1 AM. They were in session, hearing about stem cells and cloning, until 5:30. (I had to work on Friday, so I went home at 1, and didn't get to testify.) The Committee met again on Friday: for a few minutes at 8 AM and again after the House adjourned for the day. The Chair, Representative David Swinford (R- 87th District, Amarillo), was a little punch drunk from being up all night - the maximum amount of sleep he could have gotten if he'd stayed at the Capitol would have been about 2 hours.

Representative Swinford made an effort to make sure that the members were present, and all were at certain points. However, the Committee members came and went both Thursday night and Friday. In fact, Representative Farrar (D-148, Houston) didn't attend Thursday's meeting at all, and Chairman Swinford reminded her on Friday that she probably wanted to "vote against this bill."

It's possible to watch both Committee meetings on line.

Embryos and cloning on Senate agenda this week

Opponents argue that the research is unethical, because deriving the stem cells destroys the blastocyst, an unimplanted human embryo at the sixth to eighth day of development.

Michael Sandel, Ph.D. )philosopher)in the April 4, 2007 Boston Globe

WASHINGTON (Reuters) - Stem cells will be at the top of the agenda for the U.S. Senate when it returns on Tuesday with supporters of the research hoping they can change the president's mind on the issue and opponents hoping to have a say about their stand.

. . ."We got a super-majority under the Republican-controlled 109th Congress," said Sean Tipton of the American Society of Reproductive Medicine, which lobbies in support of embryonic stem-cell research.

Tipton said the current Democratic-controlled Senate will be even friendlier. "When the Senate passes this bill, the president is going to be under incredible pressure to acknowledge that the science has changed and to acknowledge that the American people support this research," he said in a telephone interview.

Washington Post April 8, 2004

"The bill is a Trojan Horse. It contains language directing the Secretary of HHS "to conduct and support basic and applied research having pluripotent potential" so long as "That the isolation, derivation, production, or testing of such cells will not involve-(1) the creation of a human embryo or embryos for research purposes"

SCNT involves just such technique. The clear implication is that under this language SCNT is "unethical." Passage of this bill would make the day for NIH funding of SCNT difficult or impossible."

Bernie Seigel, lawyer (the one who sued the Raelians for custody of their children) on Stem Cell Information blog


We will hear much about how "science has changed" since people really really want cloning and stem cell research this week.

We'll hear that it's all morals and wrong-headed religion.

We'll hear that we're killing people by opposing SCNT and embryonic stem cell research.

We probably won't hear a lot about the heart repair news, the man who's Parkinson's is improving after a trip to Asia, or all the people who receive bone marrow and umbilical cord blood cells this week.

We probably won't hear much about Dr. Atala's cells from the placenta. Or the embryonic-like stem cells from umbilical cord.



Call your Senators every day this week!

Don't bet on cloning to cure

Ian Wilmut says that if he had "to bet money," he'd bet on reprogramming adult - the patient's own stem cells.

Joining the cloning experts in the race are scientists who are looking for new ways to "reprogram" DNA, or make it young again without fusing it into an egg. They think it may be possible, for example, to bathe adult cells in the right chemicals and produce stem cells.

"In my view, it is difficult to predict which will come first but I think we need to try both," Wilmut said Tuesday. "If I had to bet money, I would probably bet on reprogramming" rather than cloning.

The science of reprogramming, he said, is moving quickly, and scientists working in the field don't have to deal with the myriad obstacles facing cloning.

The statement was made in Connecticut, at "StemCONN 07," an appropriate name that has more to do with the unethical cloning and destruction of human embryos than with the name of the State hosting the conference. Press releases, so far, attempt to focus on therapies from embryonic stem cell research - which, of course, can only benefit patients if their own cloned twin is used and destroyed in the process.

In another article in the Harford, Connecticut Courant, cloning is described as a goal, evidently, in spite of it's futility:

Wilmut and other scientists want to obtain personalized embryonic cells by fusing DNA from, say, a skin cell into an egg with its own nucleus removed. The resulting cells could be used to study a host of difficult-to-research diseases and in theory could be used to repair damaged tissue in many ailments.

However, a third article on the convention points out that

Researchers who received Connecticut's first batch of stem cell grants were among the scientists who presented their work at StemConn07.

Some of that work involves reprogramming the DNA of adult cells to produce embryonic stem cells tailored to a particular organism. This would have potentially huge implications for using a patient's own cells to repair damaged tissue without fear of rejection.

Success would quiet ethical objections to research that creates and/or destroys human embryos. Questions surrounding these techniques have resulted in a freeze on federal funding for work on stem cells created after Aug. 9, 2001.

Well, if tax money is to be used on stem cell research, they're betting a limited supply of funds in the hope of achieving cures and treatments for Texans. I agree with Dr. Wilmut in this case - the best bet is not cloning or somatic cell nuclear transfer (SCNT). It's research into non-embryonic stem cells, in order to reprogram them to make the cells each of us might need, when and where we need them.

The Courant reporter doesn't quite "get it," though. He seems to believe that the goal of "reprogramming" is to use "generic embryonic stem cells" to produce the necessary cells. The research that has been published so far indicates that the most significant factor in regeneration of stem cells from more differentiated or specialized cells is the "factors," environmental cues and conditions that stimulate and recruit the patient's own latent or limited stem cells.

Cord Blood Cells: Godsend or Gimmick?

"There are people who are alive now who otherwise would've been dead if there hadn't been a mother who donated their cord blood."

If you know me and my granddaughter Roni, you know that my answer is "Godsend."

ABC News has a video news report from Good Morning America on the current status of cord blood use. Note that one of the cases discussed is for an "immune problem." This could be a lack of immune cells or one the treatments for Rheumatoid Arthritis, lupus, and other autoimmune problems that are in Phase I and Phase II trials.

I thought about editing out the negative remarks, but I've left the article intact. Be sure and read the last section, "Public Banking Could Save Many Lives."

ABC News
Umbilical Cord Cells: Godsend or Gimmick?
Stem Cells Offer Life-Saving Treatment, but Private Storage Remains Expensive

March 22, 2007— - For most of us, our connection to an umbilical cord lasts only during our first few seconds of life.

However, for a growing number of people, umbilical cords represent a crucial lifeline even in adulthood.

Take Rhonda Kottke, for instance. On Dec. 28, 2001, at the age of 29, her doctor diagnosed the Chicago woman with leukemia.

Her treatments ravaged her immune system to the extent that if it were not replaced, she would die.

Kottke's siblings were tested, but their bone marrow was not a close enough match to hers. It was then that her doctors suggested a different course of treatment altogether -- an infusion of stem cells obtained from an umbilical cord.

The transplant came six months after her diagnosis. Today, doctors say the graft likely saved Kottke's life.

"I'm doing great, knock on wood," she told ABC's "Good Morning America." "I have no signs of leukemia in my blood. I have no sign of cancer at all. I'm as healthy as anyone else."

Kottke received her transplant from a public cord cell bank. However, many private companies offer new parents the chance to freeze their child's cord cells for personal use -- that is, if the child or a family member needs them.

But as the trend of banking cord blood continues to grow, critics say those who bank umbilical cord cells at private banks will most likely never use it.

And with an initial price tag of more than $1,000 to store the cord blood -- and yearly storage fees in the hundreds of dollars -- the cost of this biological insurance policy may outweigh the actual benefits for most.

Cord Blood a Versatile Tool

At birth, the umbilical cord is normally thrown away. But in the past few years, doctors have discovered that it is chock full of stem cells, which can be used to treat as many as 70 different diseases.

Treatments using cord blood cells are still relatively new; so far, only about 6,000 Americans have received cord blood transplants. Most commonly, the cells are used to regenerate the immune systems of patients who have received treatment for leukemia.

"Cord blood is an increasingly valuable alternative to bone marrow transplant," says Dr. Curt Freed, head of clinical pharmacology and toxicology at the University of Colorado School of Medicine.

However, researchers say that future applications could be far broader. But, though cord blood treatments appear promising, much of the science surrounding these treatments is still speculative.

"There may be technology developed in the future that allow patients and parents to find it useful in a clinical setting, but there is a lot of science needing to be performed before any of this stem cell hype becomes reality," says Bryon Petersen, associate professor of pathology at the University of Florida.

A Wise Investment?

Joshua D'Eramo's parents privately stored his umbilical cord blood when he was born. It was an expensive decision -- they paid their company $1,200 up front and $100 each year to store it.

"It's like an insurance policy," says his mother, Rena. "We get insurance for our cars, for a car accident and we may never need it, but it is comforting to know it is there if you do need it."

Today there are 25 private companies that will store a baby's cord blood for a fee. Like a bank account, it will be available exclusively to the family of the donor.

But the chances that anyone will ever need to make a withdrawal from such an "account" may be slim.

"There's nothing particularly wrong with doing that, but it's not very useful," says Dr. Cladd Stevens, medical director for the New York Blood Center's National Cord Blood Program.

"I think most of the professional organizations, the pediatric society and obstetric society, recognize that it's not very useful."

"A single individual has about a one-in-one-thousand chance of needing a bone marrow transplant in his or her lifetime, so banking does not make much sense as an insurance policy," Freed says. But, he adds, "In individual cases, such as a family member's illness that might be treated with cord blood, retaining cord blood could make sense."

Critics go one step further, saying that advertisements used by such private banks prey on the fears of new parents.

"I'm sure there are a certain amount of businesses and people with less than admirable scruples who take advantage of the public fears," Petersen says. "Those companies would blacken the eye of the business as a whole."

Public Banking Could Save Many Lives

Parents who choose not to seek the services of a private bank have another option as well -- they can donate the cord cells to a public bank, which will, in turn, donate them to those in need.

"We initially thought about private banking, and I think most parents that think about it probably do, because your first thought is 'oh, my God, what happens if something happens to my baby?'" says 35-year-old new mother Angie Bongaarts of Chicago.

But Bongaarts and her husband discussed the matter, and together they agreed that since they had no family history of leukemia, they would, instead, send their daughter's umbilical cord to a public bank.

"We figured that there was probably a better chance for the blood going for use for someone who did have a problem right now," she says.

Two-and-a-half months after they donated their baby's cord blood to a public bank, Bongaarts and her husband were notified that the cells were used to help a young man with an immune problem.

Bongaarts says the prospect that her daughter's cells may have saved someone's life was a special gift.

"I was euphoric," she says. "It's been nice to think back on for the past couple weeks, to know that we were able to do that for someone."

According to Stevens, Bongaarts' story is not unique.

"We estimate there are probably 10,000 patients around the world who have benefited from the fact that a mother donated her baby's cord blood for anybody who needed it," she says.

"There are people who are alive now who otherwise would've been dead if there hadn't been a mother who donated their cord blood."

Largely due to the success stories seen thus far with public cord cell banking, many experts say a fully stocked national registry of 150,000 samples -- a project currently in development -- could save many lives.

"With medical research progressing -- and if everyone donates cord blood to public banks -- then an excellent cell match should be available for those that need cell transplantation in the future," Freed says.

Public banking saved Kottke's life. And she says the impacts of the lifeline she received are overwhelming.

"It's absolutely the most amazing thing anyone has ever done for me," Kottke says. "I'm thankful every day."

For more information about donations, visit www.nationalcordbloodprogram.org

Copyright © 2007 ABC News Internet Ventures

HT: Bioethics.com

Texas Politics, Bias and Bioethics

"All politics is local," is a quote attributed to - and the title of a book co-authored by - the late, former Speaker of the House, Tip O'Neill.

The lesson seems to be one that Texas State Representative Juan Garcia, D-Corpus Christi, learned well. It doesn't hurt to stack the deck in your favor, either.

Evidently, the Representative held a meeting at a church in Corpus Christi, Texas and only invited the people that agreed with him to present arguments on stem cell research to a local group of clergy.

Read "stem cell research" to include embryonic stem cells from human embryos.

I'm certain that the Representative knows the names of groups who could have directed him to people like me who could make the case for the basic science and human rights issues inherent in "the stem cell debate." (Okay, I did say, "people like me.")

Instead, the clergy evidently found themselves faced with advocates who do not believe that research in stem cells and regenerative, cellular medicine can proceed without embryonic stem cells. Advocates who include representatives from State Universities and from the "Texans for the Advancement of Medical Research," a group dedicated to the advancement of destructive embryonic stem cell research and cloning.

A similar one-sided, and self-serving argument was made this week by Tom Okarma, the president of Geron, one of the biotech companies that holds the patents on human embryonic stem cells.

This, in spite of proof such as that given to the House State Affairs Committee last Monday, of children who are alive because of stem cell transplants from cord blood. And the hope of so much more from readily available umbilical cord cells: including functional liver tissue, lung cells, nerve cells and pancreatic islet cells.

Umbilical Cord Blood Saves Lives

Today, the Texas House State Affairs Committee heard from a young man who was born with sickle cell disease. Young Joseph, Jr. told the Representatives that his baby brother saved his life. And now, he doesn't have to take medicine or get shots any more. (The oblivious hero slept through the hearing.)

And of course, I told about my granddaughter who received cord blood stem cells at 15 months old from an unrelated, anonymous little boy to cure her Kostmann's nutripenia. That's her with me, last August when we testified to the Senate State Affairs Committee.

You can watch the video at the Texas Legislature Online website archived files from 3/12/07, here, beginning around 25 minutes in. (Don't miss the earlier testimony in favor of legislation to protect embryos and embryo adoption. Joseph and his family testify at 45 to 47 minutes.)

Representative Robert Puente (D- 119) presented his House Bill 709 was before the Committee and is a perfect example of the "common ground" that is possible for those of us looking for ethical ways to further (ethical, non-embryonic) stem cell research.

The Bill would require the State Department of Health Services to develop and distribute a brochure to educate expectant parents about donating and banking cord blood. We heard that there are free opportunities for all mothers and fathers to donate their child's cord blood, if they have time to make the arrangements.

We also were privileged to hear from David Harris, Ph.D., of The University of Arizona. (His testimony begins at 30 minutes on that video) Dr. Davis began the first cord blood bank, and he told us that his children were the first to have their cord blood banked at birth.

I learned quite a bit, including that there are out of State public banks that will accept cord blood stem cells from Texas, and that there is a procedure to donate blood from a private, "family" bank to the public bank.


Here's a few sites with more information:

The Texas Cord Blood Bank

The MD Anderson Cord Blood Bank

HealthBanks (a commercial health information site)

Truly transplantable lung stem cells

Researchers at The University of Michigan have proven that mesenchymal stem cells are present in the lungs, and that these cells have transplanted along with the rest of the lung.

In the past, it was believed that the mesenchymal stem cells ( a versatile group of stem cells - see the information in the quote below) were derived from the patient's lungs. We now know that they came from the donor and they they persist for years, aiding in the repair and function of the

In the cases where the donor and recipient are different genders, most of the stem cells are found to be from the donor. Some of the cells have been found more than 11 years after the transplant.

So much for the "first transplantable" claims out of Houston.

One of the most telling findings was that, in cases where the transplant donor and recipient were not of the same sex, nearly all the MSCs (about 97 percent) originated in the donor, indicating that they were present in the tissue since the time of transplantation. "We were able to isolate the cells derived from the donor as far as 11,5 years after transplantation," says Lama, assistant professor in the Division of Pulmonary and Critical Care Medicine at the U-M Medical School. "We discovered the existence of a population of MSCs that reside and self-renew in the tissues of the adult lung – something that might hold true for other organ systems as well.

"Potentially the most important outcome of our finding is that it could lead to an understanding about therapeutic options using MSCs that reside in adult organs," Lama continues. "These lung-derived cells are different from MSCs derived from bone marrow in the expression of various genes, which makes us believe that they are specific to the organ they are isolated from."

The study appears online March 8 in advance of publication in the April print issue of the Journal of Clinical Investigation.

MSCs are widely seen as a potential source of therapies for numerous diseases and conditions, such as heart disease, cystic fibrosis, graft-versus-host disease, muscular dystrophy, and as a possible source for improved recovery of cancer patients undergoing chemotherapy.

Lama’s laboratory currently is working on another study involving the lung-derived MSCs that shows potential importance of these cells in lung transplantation. That study is not yet complete, but so far it indicates a very strong ability of these MSCs to suppress the immune cells that are involved in organ rejection. In addition to helping prevent organ rejection, other possible uses for the lung-derived MSCs could be therapies related to heart attack and pulmonary fibrosis, Lama says.

MSCs are termed progenitor cells; that is, they can differentiate into only limited number of cell types such as bone, cartilage and fat cells. However, previous laboratory studies have demonstrated the beneficial effect of these cells in various diseases, such as models of heart attacks and pulmonary fibrosis.

The current study of MSCs included 172 bronchoalveolar lavage fluid samples collected and analyzed from 76 lung transplant recipients at the U-M Health System. The ability to isolate these cells with relative ease from lavage fluid is a very significant finding as it provides a potential source to isolate MSCs, says Victor J. Thannickal, M.D., associate professor of Internal Medicine in the Division of Pulmonary and Critical Care Medicine and senior author on this study. "The specific roles of these cells in chronic lung diseases are yet to be fully defined, but will be an active area of research in years to come." Source : University of Michigan Health System

Stem cell review, March 2007

It's time to write an updated review on the status of stem cell therapy.

For one thing, I wrote about the lung cells from two different labs and sources, yesterday. Next, Richard Doerflinger has written his "75 new reasons" to support non embryonic stem cell therapy over on "DO NO HARM." And then, there's the news out of China (here, at Reuter's) that a group of researchers will soon begin a large trial of cord blood stem cells in spinal cord injury has a lot of people talking.

Yesterday morning, Rep. Beverly Wooley from the Houston Area held a press conference with the local embryonic stem cells and cloning advocates to announce the latest version of her clone and kill bill, HB 2704. The bill contains the usual redefinition of "cloning" (as "implantation or attempted implantation") with a twist (" of any human embryo created by a method other than fertilization") and would create an Advisory Committee comprised of 7 scientists, 1 medical ethicist, 1 member of a religious organization (what, the rest can't go to church?), and representatives of the research centers. There is no call for treating physicians like family doctors, hematologist/oncologists, or transplant surgeons who would and do guide patients through the stem cell treatment. There is no patient or disease advocate member.

This in spite of the fact that Texas researchers are making progress, now, in real patients, treatment that doesn't depend at all on creating and killing embryos. For example, there are Drs. Cox and Baumgartner in Houston, who have been doing a study on using children's own bone marrow in trauma cases, focusing on new damage. The team is severely limited in funds for the research that could help Texas children, today.

While there is hope, what should we hope for? And what do all these studies and reports mean?

Every day, we learn more about the stimulation and recruiting of stem cells from the patient's own body and from donor cells, like cord blood.

Donations of cord blood, fat, peripheral blood, bone marrow are found much more easily and in larger numbers in practical terms, because there are more people than embryos that will ever be available for destruction, more babies being born than embryos in any lab or freezer, and because no one has to die for them.

Cord blood "unrestricted somatic stem cells" appear to me to be the most promising of all the stem cells.

The answers are obvious if you think about it -- even the "embryonic proponents" are trying to make adult stem cells.

None of the treatments involved in therapy - now or in any likely future therapies - are actual embryonic stem cells, because the cells we need will only function in specific conditions and surroundings. The specific conditions and surroundings are only found in place, in the actual site of damage.

Embryonic stem cells function is to make embryonic tissues and must develop into precursors and then specific tissues. The "gold standard" test for embryonic stem cells is their ability to make tumors called teratomas in mice. And this is what they would do in any body, as long as they are "embryonic stem cells."

The manipulations that are required to manage their development - like "transfecting" the cells with genes inserted by retroviruses, as in those lung cells from Houston (yesterday) - are themselves dangerous and risky for patients. In contrast, the non embryonic cells are much easier to manipulate and behave better in the body.

If you read the research articles, even those embryonic cells from the inner mass are not all universal cells. They have had some genes turned on and some genes turned off. The researchers select out the cells they desire by creating conditions that favor only those cells.

The trick in both embryonic and adult stem cell research is to find and support only the cells that are desired. And, again, the conditions that support the cells desired are only reliably found in the body, in site, and are best for non-embryonic stem cells and precursors.

On the other hand, "adult" or non-embryonic stem cells are found all over the body. Like the embryonic stem cells, there are many kinds. We are discovering which organs and tissues have their own stem cells in relatively large amounts, and which do not. Researchers have found precursors or other cells in bone marrow, fat, and cord cells and cord blood that can be induced to turn into the necessary cells, in numbers large enough for treatment.

The supposed advantage of embryonic stem cells - their tendency to become any cell in the body - is actually a disadvantage because they're so hard to control. And the "disadvantage" of non-embryonic stem cells - that they're already partially specialized - is what makes them easier to manipulate.

For another review of stem cell therapy, go here.

Umbilical Cord vs. Embryonic Stem Cells

The Proceedings of the National Academies of Science (PNAS) has published the article that was the subject of this blog last week, and which claims that researchers at the University of Texas at Houston have produced the "first transplantable source of lung epithelial cells." There is no evidence that these cells are "transplantable," and they are definitely not the first team to produce Alveolar Type II ("ATII") lung cells from more primitive stem cells. The article does an excellent, if technical, job of explaining the importance of ATII lung epithelial cells:

The alveolar epithelium covers [approximately] 99%of the internal surface area of the lung and is composed of two major cell types, the alveolar type I (ATI) cell and the alveolar type II (ATII) cell. ATI cells are large flat cells through which exchange of CO2/O2 takes place. They cover [approximately] 95% 0f the alveolar surface and comprise [approximately] 40% of the alveolar epithelium and 8% of the peripheral lung cells. In contrast, ATII cells are small, cuboidal cells that cover [approximately] 5% of the alveolar surface and comprise 60% of the alveolar epithelium and 15% of the peripheral lung cells. They are characterized by the unique ability to synthesize and secrete surfactant protein C (SPC) and by the distinct morphological appearance of inclusion bodies, known as lamellar bodies. Important functions of ATII cells are (i) to synthesize, store, and secrete surfactant, which reduces surface tension, preventing collapse of the alveolus; (ii) to transport ions from the alveolar fluid into the interstitium, thereby minimizing alveolar fluid and maximizing gas exchange; (iii) to serve as progenitor cells for ATI cells, which is particularly important during reepithelialization of the alveolus after lung injury; and (iv) to provide pulmonary host defense by synthesizing and secreting several complement proteins including C3 and C5 (1–3) as well as numerous cytokines and interleukins that modulate lymphocyte, macrophage, and neutrophil functions (4). Severe pulmonary diseases can be caused by deficiencies or genetic mutations in proteins synthesized by ATII cells that are important in maintaining normal lung homeostasis. For example, complete deficiency of surfactant protein B (SPB) is caused by genetic mutations in the SPB gene. This deficiency results in impaired pulmonary surfactant composition and function and is a major cause of fatal neonatal respiratory disease (5, 6). In addition, ATII cells synthesize and secrete the serine protease inhibitor alpha-1-antitrypsin (alpha-1 AT) which also plays a key role in alveolar homeostasis by regulating protease imbalance and adjusting fluid clearance (7, 8), the importance of which is supported by the association of alpha-1 AT deficiency with the development of pulmonary emphysema (9). Cystic fibrosis is thought to be primarily a disease of the upper airway and submucosal epithelia and is caused by mutations in the cystic fibrosis transmembrane conductance receptor (CFTR) (10). CFTR is an important regulator of Cl and liquid transport in the lung (11–14) and is functionally expressed by human ATII cells, strongly suggesting a critical role for CFTR in regulating ion and fluid transport in the lung alveolus in addition to the upper airway (13).

(The numbers in parentheses refer to footnotes. Also, I had to change some of the characters to words: "alpha" and "approximately")

The PNAS report and UT Houston's Press Release do not contain any note about the earlier umbilical cord blood stem cell research, although the latter was published on line and in print in Cytology, at least 2 weeks before the initial submission of the PNAS article.

Both research teams report that they followed the techniques developed and reported in the lab of another researcher, Samadikuchaksaraei, in growing, multiplying and guiding the differentiation of their primitive cells toward the more specialized lung cells that were desired. Both report the successful production of ATII lung cells, as demonstrated by the way the cells look and by demonstrating the production of Surfactant Protein C - which, in human development is only found in mature ATII cells after the unborn (or premature) child has reached 36 weeks of gestation.

The Houston team claims that one reason their process is superior to the earlier Embryonic Stem Cell research is that they were able to produce mature cells in 10 days, while Samadikuchaksaraei's team took 15 days. If the ability to produce the cells in what Wetsel, et. al., describe as a "timely manner," then it is important to note that the Minnesota team produced their mature ATII cells in 3 to 8 days.

The Houston team also claims that is possible that their new cell lines might one day be transplanted, although there has never been any research reporting the successful transplantation of epithelial cells into the lungs. Another problem is that the cells were guided to change by "transfection" with a segment of DNA that is inserted into the genes of the cells, using a retrovirus. Any use of these cells, even if anyone ever proves that we can transplant cells into the lung and cure a disease, will be complicated by years of research to prove that the gene therapy that produced these cells is safe and stable in the lungs of the patients. The authors do not give us any references to support this hypothesis.

From the Discussion section of the PNAS article:

"Lung injury due to chronic pulmonary diseases, such as chronic
obstructive pulmonary disease and asthma, and inherited genetic disorders, such as cystic fibrosis and
1-AT deficiency are leading causes of morbidity and mortality worldwide. Cystic
fibrosis and
1-AT deficiency are two of the most common inherited genetic defects affecting Caucasians. In addition, SPB deficiency is a major cause of respiratory disease and fatality in neonates. All three of these diseases are caused by single-gene defects and therefore have been logical candidates for gene therapy. However, efficient vector delivery and sufficient transgene expression needed for therapeutic benefit have remained elusive. Recent research advances indicate that gene delivery via transplantation of cells derived from human stem cells may provide an attractive alternative to viral or liposome vector based gene therapies. Moreover, transplantation of cells derived from human stem cells may prove ideal for the repair and regeneration of injured lung tissue.

Because of its ability to proliferate as well as to differentiate into ATI cells, the ATII cell is an excellent choice of lung cell for possible therapeutic use in gene delivery and repair of the alveolus.

. . . The use of ES cells as a source of transplantable cells in the lung alveolus will require the generation of significant quantities of highly pure ATII cells. To achieve this goal, we chose to genetically modify hES cells so that resulting differentiated ATII cells could be enriched through antibiotic selection. Our approach was to establish a stable transfected hES cell line containing a single copy of the human SPC promoter-Neor fusion gene. When subjected to differentiation in vitro, it was hypothesized that ATII cells derived from this genetically modified hES cell line (SPCP/NEO.74) would express the Neor gene and would therefore survive G418 antibiotic selection, whereas, all of the other differentiated cell lineages as well as the pluripotent cells would be eliminated by G418 selection. Immunocytochemical and flow cytometric analysis of the surviving G418-selected cells supported this hypothesis, indicating that this genetic selection approach resulted in an enrichment of hES-ATII cells to 99% when cultured on Matrigel-coated plates. Our protocol reproducibly produced from each 10-cm culture dish 106 essentially pure ATII cells within 15 days of differentiation. These differentiated ATII cells survive for at least 2 days in culture in the absence of G418 and will provide in a timely manner sufficient numbers of pure ATII cells for future transplantation investigations."

(No footnote references were removed from this quoted portion.)


The abstracts are available on line for free, but the actual articles are available only by subscription or by paying for temporary access:

From Proceedings of the National Academies of Science, published online March 2, 2007

"A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells"

Dachun Wang, David L. Haviland, Alan R. Burns, Eva Zsigmond, and Rick A. Wetsel. Research Center for Immunology and Autoimmune Diseases and Laboratory for Developmental Biology, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center; Department of Biochemistry and Molecular Biology, University of Texas Medical School; and Cardiovascular Sciences Section, Department of Medicine, Baylor College of Medicine. Communicated by C. Thomas Caskey, University of Texas Health Science Center, Houston, TX, January 4, 2007 (received for review November 22, 2006)

Alveolar epithelial type II (ATII) cells are small, cuboidal cells that constitute 60% of the pulmonary alveolar epithelium. These cells are crucial for repair of the injured alveolus by differentiating into alveolar epithelial type I cells. ATII cells derived from human ES (hES) cells are a promising source of cells that could be used therapeutically to treat distal lung diseases. We have developed a reliable transfection and culture procedure, which facilitates, via genetic selection, the differentiation of hES cells into an essentially pure (>99%) population of ATII cells (hES-ATII). Purity, as well as biological features and morphological characteristics of normal ATII cells, was demonstrated for the hES-ATII cells, including lamellar body formation, expression of surfactant proteins A, B, and C, alpha-1-antitrypsin and the cystic fibrosis transmembrane conductance receptor, as well as the synthesis and secretion of complement proteins C3 and C5. Collectively, these data document the successful generation of a pure population of ATII cells derived from hES cells, providing a practical source of ATII cells to explore in disease models their potential in the regeneration and repair of the injured alveolus and in the therapeutic treatment of genetic diseases affecting the lung.
Keywords: complement , differentiation, surfactant proteins, alpha-1-antitrypsin, cystic fibrosis transmembrane conductance receptor

And here's the abstract of the report from November in Cytotherapy, (2006) Vol. 8, No. 5, 480-48 (Note the association with BioE, Inc., the company that's doing the cancer research with MD Anderson):

"Differentiation of umbilical cord blood-derived multilineage progenitor cells into respiratory epithelial cells."

MJ Berger, SD Adams, BM Tigges, SL Sprague, X-J Wang, DP Collins and DH McKenna, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota, USA, Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Minneapolis, Minnesota, USA, and BioE Inc., Saint Paul, Minnesota, USA

Background - Umbilical cord blood (UCB) has been examined for the presence of stem cells capable of differentiating into cell types of all three embryonic layers (i.e. endo-, ecto- and mesoderm). The few groups reporting success have typically confirmed endodermal potential using hepatic differentiation. We report differentiation of human UCB-derived multipotent stem cells, termed multilineage progenitor cells (MLPC), into respiratory epithelial cells (i.e. type II alveolar cells).
Methods - Using a cell separation medium (PrepaCyte-MLPC; BioE Inc.) and plastic adherence, MLPC were isolated from four of 16 UCB units (American Red Cross) and expanded. Cultures were grown to 80% confluence in mesenchymal stromal cell growth medium (MSCGM; Cambrex BioScience) prior to addition of small airway growth medium (SAGM; Cambrex BioScience), an airway maintenance medium. Following a 3 - 8 day culture, cells were characterized by light microscopy, transmission electron microscopy, immunofluorescence and reverse transcriptase (RT)-PCR.
Results - MLPC were successfully differentiated into type II alveolar cells (four of four mixed lines; two of two clonal lines). Differentiated cells were characterized by epithelioid morphology with lamellar bodies. Both immunofluorescence and RT-PCR confirmed the presence of surfactant protein C, a protein highly specific for type II cells.
Discussion - MLPC were isolated, expanded and then differentiated into respiratory epithelial cells using an off-the-shelf medium designed for maintenance of fully differentiated respiratory epithelial cells. To the best of our knowledge, this is the first time human non-embryonic multipotent stem cells have been differentiated into type II alveolar cells. Further studies to evaluate the possibilities for both research and therapeutic applications are necessary.
Keywords - endodermal differentiation, respiratory epithelium, stem cells, umbilical cord blood.

The key to stem cell research (no one dies)

Every living cell in our bodies has the whole set of genes that it took to grow us from a one cell embryo to the beautiful blogging people that we are now. It's just that the whole set is never working at any one time. Our growth, development, abilities and repair depend on whether a certain gene or set of genes is turned on or off by (what I think of as) the addition of keys and locks and cushions.

We constantly hear about the embryonic stem cell's ability to "develop into every cell in the body" (and all those pesky tumors when they're used in animals), as well as the trouble getting adult stem cells to work fast enough to repair damage. There's also the problem of aging, which is really just when our body can't replace dying cells as fast as we lose them, added to the fact that the cells themselves seem to die sooner and more often.

Epigenetics are the influences in the cell that turn certain genes on and others off. And they are the hot topic in the serious study of stem cells, embryology and medicine.

Stem cells rely heavily on epigenetic signals. As a stem cell develops, chemical tags on the DNA or its surrounding histone proteins switch genes on or off, controlling a cell’s fate.

You may hear of "methylation" or "imprinting" of genes. These chemical processes are how the DNA program within the nucleus of the cell - the blueprint and instructions for what the cell will do today or for the rest of its life - is set. They are the "epigenetic" conditions that fold away some genes and expose some others so they can be read.

One of the cushions is the telomere. After Dolly the sheep was cloned, we heard about telomeres - the repeating tags on genes that make the difference between a gene being young or old. I think of the string of telomeres as a roll of postage stamps. Each time you send a letter, you use a stamp, and eventually you don't have any.

In the same way, genes lose telomere segments when they are copied. Eventually, there are not enough telomeres to make the gene copying system kick in. But, sometimes, telomeres can be added by the cell's system and sometimes they aren't lost at all during copying.

What if you could go to the telomere office and buy a new roll or, better yet, if you could just make the ones you need in your own cells, when and where you need them?

Public Cord Blood Banks

Georgia Senator Shafer has introduced a bill that would make that State the first to dedicate funds to a public bank for both cord blood and placental and umbilical cord tissues. This follows a move across the country to begin public, rather than private, cord blood banking for therapy and research.

MD Anderson (MDA), our big cancer research and therapy center in Houston, Texas, has announced that it has received $9 million from the Federal Health Resources and Services Administration to support their Cord Blood Bank. MDA is already collecting units at two hospitals in the area.
The Texas Cord Blood Bank has been growing since a push by then Representative, now State Comptroller, Elizabeth Ames Jones and our Governor Rick Perry led the move to dedicate State funds. The first $1 million dollars in Federal money was matched by State money and again by private donations. In 2005, Governor Perry awarded a grant of an additional $1.2 million in matching funds (meaning that the grant will match each dollar donated from private donors). TCCB is currently collecting cord blood at 4 hospitals, one in North Dallas, one in San Antonio, and at hospitals in two cities in the Rio Grande Valley. (See the video on the Cord Blood Bank at Jones' campaign website.)

I'm convinced that cord tissues contain the stem cells that will offer all the therapies and hope that we hear about from the advocates of destructive embryonic stem cells. And we're throwing them away, every day.

Language change alert ("Embryonic" at 8 weeks)

We were due, I guess. We went through the redefinition of pregnancy (implanted in a uterus"), embryo (after 14 days or implanted in a uterus), cloning (therapeutic cloning, then somatic cell nuclear transplantation, nuclear transplantation, patient specific stem cells, production of "early stem cells, etc.)

And now, we're supposed to move the line of "embryonic" to eight weeks of gestation.

And we should just forget all the past promises about "14 days," implantation, along with our objections to killing the youngest of our children.

Some of us have warned that embryonic stem cell research, with it's high risk of teratomas - tumors that (to paraphrase a popular slogan) "contain all the cell lines in the body," would lead to further maturation of human embryos into the fetal stage of development. Since the goal is usable tissues and stem cells, it made sense to us that researchers will eventually get around to demanding for funding to grow the embryos in human or surrogate wombs in order to "save lives," and further their grant requests.

There have been previous examples (I'm on my way to a meeting, so the references will have to wait 'till tonight) in production of "embryonic" nerve tissues being used to treat a few children with neurological metabolic diseases. In fact, the "embryonic" tissues used to harvest these cells must come from children who are aborted at 7 to 9 weeks, technically fetuses, not embryos.

Further evidence of the possible direction of stem cell research - if we allow it - comes to us this week, from the online journal, PLOS-Medicine.

Here's the press release that showed up in my Google alerts file, from Eureka News Alerts, "Human stem cell transplants mature into neurons and make contacts in rat spinal cord.":

Human stem cell transplants mature into neurons and make contacts in rat spinal cord

Human nerve stem cells transplanted into rats' damaged spinal cords have survived, grown and in some cases connected with the rats' own spinal cord cells in a Johns Hopkins laboratory, overturning the long-held notion that spinal cords won't allow nerve repair.

A report on the experiments will be published online this week at PLoS Medicine and "establishes a new doctrine for regenerative neuroscience," says Vassilis Koliatsos, M.D., associate professor of neuropathology at Johns Hopkins. "The spinal cord, a part of the nervous system that is thought of as incapable of repairing itself, can support the development of transplanted cells," he added.

"We don't yet know whether the connections we've seen can transmit nerve signals to the degree that a rat could be made to walk again," says Koliatsos, "We're still in the proof of concept stage, but we're making progress and we're encouraged."

In their experiments, the scientists gave anesthetized rats a range of spinal cord injuries to lesion or kill motor neurons or performed sham surgeries. They varied experimental conditions to see if the presence or absence of spinal cord lesions had an effect on the survival and maturation of human stem cell grafts. Two weeks after lesion or sham surgery, they injected human neural stem cells into the left side of each rat's spinal cord.

After six months, the team found more than three times the number of human cells than they injected in the damaged cords, meaning the transplanted cells not only survived but divided at least twice to form more cells. Moreover, says Koliatsos, the cells not only grew in the area around the original injection, but also migrated over a much larger spinal cord territory.

Three months after injection, the researchers found evidence that some of the transplanted cells developed into support cells rather than nerve cells, while the majority became mature nerve cells. High-powered microscopic examination showed that these nerve cells appear to have made contacts with the rat's own spinal cord cells.

###

The research was funded by the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association and the Robert Packard Center for ALS Research at Johns Hopkins.

Authors on the paper are Jun Yan, Leyan Xu, Annie M. Welsh, Glen Hatfield and Koliatsos, all of Hopkins, and Thomas Hazel and Karl Johe of Neuralstem of Rockville, Md.

On the Web:

http://neuroscience.jhu.edu/VassilisKoliatsos.php
http://www.plosmedicine.org
http://pathology2.jhu.edu/disease/home_files/page0003.htm

There is nothing alarming - and quite a bit that's encouraging - in that press release. However, reading the actual published articles leads to the discovery that the stem cells in question come from human fetuses. I'm afraid that I don't know of any way to harvest neural stem cells from human fetuses without harming those unborn children.
Here's the first article, "Extensive Neuronal Differentiation of Human Neural Stem Cell Grafts in Adult Rat Spinal Cord."

And the second, which explains where we are going:"Making Human Neurons from Stem Cells after Spinal Cord Injury"

Spinal cord cells were obtained from cervical and upper thoracic spinal cord of an eight-week-old human embryo and expanded in monolayer culture in defined medium with the mitogen FGF2 (a member of the fibroblast growth factor family).

(Emphasis mine)

In the future, perhaps fetal neural stem cells can be developed from cells harvested from placentas collected after the birth of children or as a by-product of amniotic fluid tests done for medical indications and then used as we use other cellular and tissue transplants of adult stem cells and specialized tissues.

Perhaps Dr. Atala and his research group could follow this line.

However, I expect to see a call for more money for fetal stem cell research and for a demand for an expansion of the time that human "extracorporeal" embryos can be maintained.

And won't it be interesting to see how these nascent human beings are grown to eight weeks or so?

$17.9 Million plus for Texas: ethical stem cells

The UT Austin Daily Texan has the only report that I can find in the news about Wednesday's announcement that the University of Texas Health Center in Houston is the recipient of $17.9 million for stem cell research on treatments for heart disease.

The National Heart Lung and Blood Institute granted $17.9 million for the research of stem-cell treatments for cardiovascular disease to the UT School of Public Health Coordinated Center for Clinical Trials.

The school was established in 1967 as part of the UT Health Science Center in Houston.

The new funding will bring the institution to the forefront of stem-cell, cardiovascular research. Charged with coordinating the network's participating centers, the school will serve as the hub for the Cardiovascular Cell Therapy Research Network.

"This research will examine the promise of approved stem-cell research of cardiovascular disease," Dr. Lemuel A. Moye said.

The network's centers include the University of Florida, the Cleveland Clinic, the University of Minnesota, the Texas Heart Institute and Vanderbilt University. Dr. Lemuel A. Moye, biostatistics professor and principal investigator of the program at the UT School of Public Health, was excited that the institution was selected to coordinate the other centers.

"It was a pleasant surprise," he said.

I wonder whether this grant will help one of the Houston Health Center Hospitals begin collecting cord blood?

Or will the docs at the UT School of Public Health work with Dr. Willerson and Dr. Perin at the Texas Heart Institute, who are testing a system to select progenitor cells to repair heart tissue, using a commercial product, Aldagen?

Hopefully there's a coordinating board somewhere that's watching over the efficiency of these different research groups.