Texas Legislators Seek to Limit Funds for Human Embryo Destruction

Senator Steve Ogden is a Texas Hero!

Sen. Steve Ogden, R-Bryan, though, said critics exaggerate what his 24-word "budget rider" would do. He said it simply assures that the budget's $700 million for research doesn't underwrite destruction of embryos.

"There is a significant moral concern amongst many Texans that a human embryo really meets every scientific definition of human life that's out there and that we shouldn't be using human embryos for scientific experiments," Ogden said.

The dispute flared early last week. The Senate Finance Committee, which Ogden heads, took only two minutes late Monday to consider his rider. It says, "No funds appropriated under this act shall be used in conjunction with or to support research which involves the destruction of a human embryo."

The provision was adopted, 6-5, with Sen. Robert Duncan, R-Lubbock, joining four Democrats against.

The Dallas Morning News reports (free registration required) that some Texas embryonic research advocates claim this move will "embarrass" Texas. Of course, they also claim that embryonic stem cell research only involves "embryos that would be discarded, any way" Since we know that much of the research involves specially created, "disease specific" embryos, the latter is false.

And so is the first objection. Every week, we are reading about new ways to reprogram adult cells to achieve the stem cells that are needed to study and treat disease without ever going near an embryo. Former proponents of embryonic research and producers of new embryos for stem cell research like George Daley are switching their focus toward non-embryonic research. Texas researchers have been early stars in this research, among the first to using umbilical cord blood for stem cell research.

Texas doesn't need to waste our money following the false trail of embryonic stem cell research when there is so much promise in more treatments, sooner, from non-destructive and non-embryonic research.

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.

UTexas: Modified virus fights stem cell cancer

Viral gene therapy (similar to techniques used in the stem cell breakthrough last week) has been used by University of Texas MD Anderson Cancer Center researchers in animal models and reported in the September 19, 2007 issue of the Journal of the National Cancer Institute. From MD Anderson:

Since 2004 scientists have found that brain tumors are driven by haywire stem cells that replicate themselves, differentiate into other types of cells, and bear protein markers like normal stem cells.

"Research has shown that these cancer stem cells are the origin of the tumor, that they resist the chemotherapy and radiation that we give to our patients, and that they drive the renewed growth of the tumor after surgery," Fueyo said. "So we decided to test Delta-24-RGD against glioma stem cells and tumors grown from them."

Researchers used a virus to infect the cells of aggressive tumors of the cells that support brain cells, glioblastoma multiforme. Gliomablastomas are 60% of brain cancers and patients have a survival rate as short as 2 to 3 months, with less than 10%-25% survival after 2 years even with current aggressive therapy. The virus is modified so that it is "selective" for cancer: it only infects the cancer tumors and cannot infect others.

The team first developed mice with transplanted human brain cells derived from stem cells found in four samples of glioblastoma multiforme. The researchers then developed a customized virus, Delta-24-RGD, to fight the cancer. According to a 2003 MD Anderson press release on the trials, the virus infection inserts copies of a certain gene, retinoblastoma protein (Rb), that acts as a "brake" on the cell duplication system of the cell. In order to make the therapy more efficient and safer, the virus also insert a gene to for a cell surface receptor, a sort of "docking" area on the outside of the cell.

The cell surface receptor for viruses is one of the ways that we are studying to fight both cancers (see this free article from this month's JNCI) and viral infections, themselves. The goal is vaccinations to affect genetic causes of cancer (as in these two reports) or to prevent viruses from binding to the cells and infecting them in the first place.

Cutting Edge Juvenile Diabetes Adult Stem Cell Research

Interrupting our discussion on State force and conscience, but this news is just too cool to postpone:

Regenetech, the company that has the license agreement with NASA for the "Intrafuge" that processes cord blood cells and bone marrow cells for the production of embryonic-like and select stem cell treatments, has announced a two year agreement for research with Johns Hopkins, on Type 1, insulin-dependent or Juvenile Diabetes:

Regenetech®, Inc. announces that it has signed a Sponsored Research Agreement (SRA) with Johns Hopkins University in order to work toward a treatment for type 1 diabetes. This is in addition to the research agreements which the Company currently has in place with Texas A&M University and the University of Texas Medical Branch at Galveston. Regenetech is pioneering the development and commercialization of technology which the company believes will enable regenerative therapy with adult stem cells for widespread use.

Regenetech’s agreement with Johns Hopkins University will span over two years, and involves significant funding from the Company. The goal of the research project is to develop a treatment for type 1 diabetes using a patient’s own adult stem cells expanded in Regenetech’s IntrifugeTM Bioreactor. Dr. Mehboob Hussain, Assistant Professor of Pediatrics and Medicine at Johns Hopkins University, has considerable experience in the treatment of diabetes with stem cells, and is overseeing the research which will use Regenetech’s technology.

University of Texas Medical Branch at Galveston (UTMB) supplies blood and cord blood stem cells to Regenetech’s laboratories and uses them for their own research purposes as well. In addition, the Company has signed a sub-license agreement with UTMB to use Regenetech’s NASA licensed IntrifugeTM Bioreactor system to expand the stem cells found in the blood. The ultimate goal is to provide low cost, safe doses of adult stem cells for a broad range of diseases and known therapies. The principal investigator from UTMB is Professor Larry A. Denner, who has significant expertise in the identification, expansion and differentiation of primitive cord blood stem cells for pre-clinical studies.

Regenetech also has a SRA with Texas A&M University for the treatment of bone fractures in animals. The research is to demonstrate the clinical efficacy of NASA’s patented time-varying electromagnetic field (TVEMF) technology, which is exclusively licensed to Regenetech. This technology holds rapid healing potential for animals, such as high value race horses and pets, which offer highly significant markets for Regenetech. Once the veterinary treatment protocols have been finalized successfully, it is expected that they will lead the way to human clinical trials.

Regenetech also has a good stem cell "primer," as well as more information on their ongoing research and patents. They do make a case for embryonic stem cells, saying that adult stem cells haven't been found for all tissues and organs and that it might take too long in emergency situations to grow the needed tissues, but do not acknowledge that these limitations also exist for embryonic stem cells.

Oh well, no one's perfect.

Previous review Texas Cancer and stem cell research

Here's a link to a post from last January on HB 14, and House Joint Resolution 90, the Bills which became Proposition 15, the Legislation for $3 billion in cancer research bonds and the Texas Cancer Prevention and Research Institute of Texas.

The original article is no longer available on the Austin American Statesman site, but here's another article on the debate:

From the San Antonio Express-News, November 3, 2007,

Unlike the California initiative, which was enmeshed in controversy — and litigation — over potential conflicts in its governing board, Proposition 15 would create a new entity — the Cancer Prevention and Research Institute of Texas — that would operate with two advisory boards. A scientific group would decide which research ideas merit funding, while a panel of 11 political appointees would provide oversight.

Political appointees would be restricted from decisions about institutions to which they have ties. And they could overrule the scientists on individual grants only with a two-thirds majority vote. The governor, lieutenant governor and speaker of the House each would appoint threepanel members. The other two would be the governor and state comptroller, or their delegates.

Local communities have been moving to put together lists of local candidates in the event the measure passes, believing the panel would make sure the money is distributed fairly across the state, rather than simply handing most of it over to the University of Texas MD Anderson Cancer Center — Texas' 600-pound gorilla of cancer research. The Greater San Antonio Chamber of Commerce's health care and bioscience committee would recommend John Kerr, president of the Southwest Foundation for Biomedical Research; and Phyllis Browning, CEO of Phyllis Browning Co.; as well as a slate of top local cancer experts for the scientific panel, said Ron Tefteller, who chairs the committee.

Local cancer researchers acknowledge that even with all that, they'll be at a competitive disadvantage with their neighbors to the east — as well as other Texas research institutions with a richer pool of benefactors. The law would require that researchers find matching funds equal to half the amount of the grant they're seeking under the program — "skin in the game," Nelson calls it.

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!

Texas Researchers: Prostate Pluripotential Stem Cells

Researchers Dr. Liping Tang from the Bioengineering Department at University of Texas at Arlington, and Dr. Victor K. Lin of the Department of Urology at UT Southwestern (Dallas, Texas) have published a paper describing pluripotent adult stem cells from prostate tissue. Tissue cultures as well as biochemical markers show that the cells harvested from men undergoing surgery to remove the prostate contained mesenchymal adult stem cells that could be induced to grow the smooth muscle cells that they become in the prostate. In addition, they were induced, in the laboratory, to become stem cells that gave rise to fat cell lines ("adipogenic") and bone cell lines ("osteogenic" cells).

The men did not have prostate cancer. They had BPH, "Benign Prostatic Hypertrophy," (or "Hyperplasia")which is an overgrowth of the prostate tissue, a donut of tissue that surrounds the urethra of men, blocking or restricting the passage of urine from the bladder to the outside.

It's exciting for researchers to not only report research that may help in the treatment or prevention of a disease that affects many older men, but to also find stem cells that are easy to grow and which give rise to several different lineages of adult cells from a common precursor cell.

From the (free) abstract in The Prostate:

Our study on primary stromal cells from BPH patients have yielded many interesting findings that these prostate stroma cells possess: (1) mesenchymal stem cell (MSC) markers; (2) strong proliferative potential; and (3) ability to differentiate or transdifferentiate to myogenic, adipogenic, and osteogenic lineages. These cell preparations may serve as a potential tool for studies in prostate adult stem cell research and the regulation of benign prostatic hyperplasia. (Emphasis mine.)

For an easier to read explanation, read the Press Release from the University of Texas at Arlington School of Engineering:

The research team was particularly interested in human pluripotent stem (hPS) cells, which are the primary cultured BPH stromal cells and have two unique characteristics; they do not exhibit markers typical to epithelial cells (covering the lining of body tissue) and have few markers for disease-causing smooth muscle cells.

This study on primary stromal cells from BPH patients resulted in findings that prostate stroma cells possess multipotent stem cell markers, strong proliferative potential and the ability to differentiate or transdifferentiate to muscle-forming, fat-forming and bone-forming lineages. These cell preparations may serve as a potential tool for prostate stem cell research and its role on regulation of prostatic hyperplasia.

(Hat Tip to DT of daily transformation.)

NEJM comments on Texas "futile care"

The New England Journal of Medicine has a "Perspective" article commenting on the Emilio Gonzales case in Austin, Texas It's available free online, and there's an audio interview with the author.

The comments are very specific on the ethics of the case, and the author does a good job of outlining the Texas Advance Directive law, the various reasons given by the doctors who refuse to carry out the surrogates' wishes in these sorts of cases, and some of the objections to the ethics committees that decide whether or not the doctor's refusal to follow the surrogate's wishes is ethically appropriate. There's also a link to another free article that details findings about the "burnout" of ICU nurses.

Austin Texas Patients In Adult Stem Cell Research

The Austin, Texas TV station, KEYE, has a report on the research trial using donated adult stem cells from bone marrow in patients within 10 days of a heart attack. (I've highlighted the part about the bone marrow.)

Seema Mathur
Reporting

(CBS 42) AUSTIN

A clinical stem cell trial involving Austin patients has some doctors saying it may change medicine forever.

The trial involves heart attack patients using adult stem cells. The stem cells are from the donated bone marrow of healthy adults.

The trial is in its first phase, with just 10 sites around the nation. Doctors are already saying the results hold the promise of doing what has never been done before, rebuilding heart muscle of heart attack patients.

Ben Calvo, a math teacher, was willing to take what he considers a calculated risk. He's one of 53 heart attack patients in the nation taking part in an adult stem cell clinical trial.

“I don't feel like a guinea pig,” Calvo said. “I don't want to say I feel super human, but I feel just great.”

Dr. Roger Gammon is director of research at Austin Heart, cardiologist providers in Central Texas. He says that in the double blind study, within 10 days of a heart attack, some patients received adult stem cells from donated bone marrow and other patients received a placebo.

“We hang a bag that has millions of stem cells in it,” Gammon said. “They infuse through the vein and travel to where there is an injury. It's just a simple intravenous infusion over 30 minutes.”

Calvo thinks he received the real thing. According to recent images of his heart, so does Gammon.

“Now, his whole heart is moving well,” Gammon said.

The image of Calvo’s heart is amazing because, up until this study, nothing could repair damaged heart muscle.

“They don’t just patch the problem, they actually become heart tissue that starts beating,” Gammon said.

“I feel that I can breathe better,” Calvo said.

Gammon says there was no rejection. He says some patients also had unexpected improved lung function and less irregular heartbeats.

“There seems to be an amazing homing mechanism with these cells to where they can figure out where there is an injury in your body and they go there and start to heal it,” Gammon said.

Calvo believes healing heart muscle is exactly what he experienced. Calvo also had some stents put in after his surgery.

Before this can become an approved treatment, many more people need to be studied to see if the results continue to be promising. But if they do, Gammon suspects this treatment may also help other inflammatory conditions like Alzheimer’s.

(© MMVII, CBS Broadcasting Inc. All Rights Reserved.

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)

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.

Embryonic SC researchers claim doubtful "first"

Beware of Press Release science reporting - the job of the news release or public affairs department of an institution is to get publicity, not to promote scientific knowledge. There's no peer review until after the fact, and the goal is to catch our attention, rather to educate.

A case in point was the announcement yesterday from the the University of Texas at Houston Brown Foundation's Institute of Molecular Medicine researchers' Press Release that begins:

UT Scientists Develop Promising New Procedure To Differentiate Human Embryonic Stem Cells

HOUSTON – (Feb. 26, 2007)—Molecular scientists at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM) – which is part of the University of Texas Health Science Center at Houston – have developed a new procedure for the differentiation of human embryonic stem cells, with which they have created the first transplantable source of lung epithelial cells.

The process, created in the laboratory of Rick A. Wetsel, Ph.D., a professor of molecular medicine at the IMM, is described in this week’s edition of the Proceedings of the National Academy of Sciences (PNAS). Research scientist Dachun Wang, M.D., is lead author of the article, “A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells.”

“We have developed a reliable molecular procedure which facilitates, via genetic selection, the differentiation of human embryonic stem cells into an essentially pure population of lung epithelial cells,” said Wetsel, noting the procedure also can be used to create other types of highly-specialized cells.

The word that seems to carry the most weight in that first paragraph is "transplantable." And a lot depends on how they define that word.

Since I can't find any mention of the article on the internet, except in the press releases, I'm not sure exactly what "transplantable" cells means to these guys.

However, I am convinced that they are not the only ones to derive alveolar II lung epithelial cells from stem cells.

As reported, here and very few other places, last November 1, 2006 - you know, just before the Midterm election and Missouri's disaster with the clone and kill bill - researchers at the University of Minnesota Medical School at Minneapolis published a report in Cytotherapy on their production of functioning alveolar II epithelial lung cells, capable of producing surfactant, from a certain population of umbilical cord blood stem cells:

BackgroundUmbilical 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 lightt 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.

Unfortunately, most of the sites that are picking up the PR are just publishing it whole, without evaluation or editing.

For instance, ScienceDaily, one of my favorite science news sites, published the intact, clearly labeled "Press Release", although that site also published the press release on the earlier, UCB stem cell derivation of alveolar II cells.

So far, I've only seen one note on the UT announcement that distills the info available to the news, without the hype. LongevityMeme, a blog devoted to technology and science showing promise for the extension of the human lifespan, has not duplicated the silly "transplantable" or "first" claims. The post explains the pertinent points very well (click to the original for the embedded links):

Examples of continually improving control over stem cells have been rolling in of late; here is one from the University of Texas: "We have developed a reliable molecular procedure which facilitates, via genetic selection, the differentiation of human embryonic stem cells into an essentially pure population of lung epithelial cells ... the procedure also can be used to create other types of highly-specialized cells. ... The method involves the use of protein markers under the control of cell-specific promoters to convert undifferentiated human embryonic stem cells into highly-specialized cells. The human embryonic stem cells were cultured on specially coated dishes and transfected with a lung epithelial gene regulator of a drug selection gene. ... It is a general technology for developing select cells from human embryonic stem cells. The technology has allowed us to develop a platform that could potentially be useful in the development of spinal cord cells, heart cells, nerve cells and others. ... transplantable alveolar epithelial type II cells can be explored as treatments for pulmonary genetic diseases, acquired lung disease, as well as lung trauma caused by car accidents, gunshot wounds and sports injuries. ... These are the cells that can potentially be used for regenerative lung repair."

(emphasis is mine)

The "transfected gene" treatment used to induce the embryonic stem cells to develop along the desired line appears to me to be a step that will complicate the testing and approval of the use of these cells in humans. I'm not convinced that surgery will be the optimum use of the outcome of stem cell regenerative medicine. I'm convinced that we will use what we learn to induce, stimulate and and recruit the body's own regenerative stem cells in place, as we need them

If the transfected gene is safe, then, perhaps it will be the treatment in the future. Or, perhaps the UT lab and the UM lab can collaborate on truly transplantable cells, if necessary.

Do not look behind the curtain! (again, with the magic tricks)

I'd say the man who said this needs both a heart and a brain:

"Ultimately, human hearts, human brains, and human kidneys and human pancreas will be re-created in their entirety from human embryonic stem cells or some combination of adult and embryonic stem cells," Willerson said.

He's certainly got enough nerve.

Tell me what happens when you get a new brain, in its "entirety," Doctor.

On the other hand, there's this brilliant man who's using the brain and heart he's got:

Dr. Karel Dicke, an oncologist at the Arlington Cancer Center, uses stem cells found in patients' bone marrow to ease their recovery from high-dose chemotherapy.

Dicke, who has conducted research into adult stem cells for more than 40 years, said he opposes the use of public funds for embryonic stem-cell research because it doesn't have enough public support. He echoed statements from opponents of such research in noting that the field may not be as promising as some have predicted.

"It is not that far along yet," Dicke said. "Scientists are making political statements."

Of course, it's really all about the money. As I've said before - stem cell therapy of the future will not depend on the destruction of embryos. The goal will be to use the patients' own stem cells in site, when and where they are needed. Umbilical cord and placental cells are plentiful and have shown themselves plastic enough to provide the tissues and organs that we will need. (Where the repair cannot be made in situ. Edited, March 19, 2007. BBN)

Researchers in Minnesota have produced beating heart muscle from stem cells taken from the hearts of rats. In humans, they say they are using muscle from the legs to heal hearts in place.

Have a look at more stem cell advances in this article.

Dr. Anthony Atala's group at Wake Forest University grew nerve stem cells that homed in to the areas of the brain where they were needed. Last year, Zurich researchers reported work to develop heart valves for babies from their amniotic stem cells, even before they were born.

We don't need the smoke and mirrors, Doctor Willerson. You and others have already shown us that we already have a future without embryonic stem cells.

Texas researchers discover key to heart repair

Texas research team has published a report on the fusion of adult stem cells to damaged heart cells which enables healing of damage. In this case, the stem cells are from peripheral blood - the blood that circulates every day. Presumably, the origin of these cells is the bone marrow.

The review at Physorg.com. includes a discription of the current knowledge on heart repair and stem cells. Quoted is T.H.Yeh, M.D. one of the team from M. D. Anderson, the Texas Heart Institute at St. Luke's Episcopal Hospital and The University of Texas Health Science Center at Houston.

Because many of the drugs and therapies used to treat cancer can cause heart damage, M. D. Anderson, a world-renowned cancer therapy and research center, also invests in the study of heart disease.

Cardiac adult stem cells seem to do two different things: they divide to form blood vessels and they fuse to injured heart muscle cells or "cardiomyocytes" to cause the muscle cells to demonstrate "stemness." The original fused cells are now like very special stem cells that are cardiomyocytes that can divide and multiply for months, in order to repair the damage in the heart. Until recently, we were taught that heart muscle cells did not replicate and replace themselves in adults.

Yeh and his co-workers report on adult heart stem cells, three specific proteins, the mechanisms that stimulate their production, and evidence as to how these proteins and stem cells work after heart muscle damage. Two of the proteins, described as "sticky" similar to the two tapes in Velcro, are newly discovered by the team. Another protein, vascular endothelial growth factor or VEGF, was previously known to aid in the development of new blood vessels. In hearts, VEGF causes some of the stem cells to produce blood vessels rather than fuse to the damaged muscle cells. By a series of experiments using antibodies against the proteins in immune deficient mice with induced heart damage, the team has demonstrated one way the heart repairs itself and that the same adult stem cells can lead to new heart blood vessels and new heart muscle cells. The hope is that this discovery will allow us to increase the amount of repair in heart attack patients.

The abstract of the original article published in Circulation Research OnLine First, is available for free, here. The supplemental data and some figures are also available free, here.

The last author of the original article is James Willerson, M.D., the President of the University of Texas Health Science Center at Houston, and the man who went off to Brazil in order to do one of the first studies of bone marrow stem cells used to treat heart disease. He's been mentioned on this blog, here and here.
Unfortunately, Willerson is often quoted advocating the creation of new embryonic stem cell lines, and the destruction of more and more human embryos in order to harvest those lines.