!Safe! Induced Pluripotent Stem Cells

Robert Lanza is now reporting that his research group has produced induced Pluripotent Stem Cells (iPS) that are safe for use in humans. The website, Red Orbit, has provided a link to the original (.pdf)article. See the Time magazine news article, here.

Lanza gives credit to the pioneering work of Shinya Yamanaka:

Dr. Robert Lanza, chief scientific officer at Advanced Cell Technology (ACT), reported today in the journal Cell that his team has created stem cells using human skin cells and four proteins. The innovation builds on the breakthrough discovery in 2006 by Shinya Yamanaka, who similarly coaxed human skin cells to revert to a pristine, embryonic state by introducing four key genes into the cells, piggybacked on viruses.

The technique relies on proteins that induce reprogramming of the cells, rather than genes or viruses. These appear to function in a manner analogous to the stimulating factors that are currently the standard of care for low blood cell counts: The body - in this case, the cell - begins to function the way it's wanted when certain proteins are introduced.

In this study, patients' own skin cells were harvested by a small biopsy. Approximately one in 10,000 of those cells were induced to revert to the embryonic stage. While this 0.001% seems a minute fraction, it's much more significant and achieveable than the production of patient-specific cells from cloned embryos, where each cell line would require multiple donor oocytes - "eggs" - harvested from women. Obtaining those oocytes has not proven very easy, even without the ethical problem of creating and destroying a human embryo that is the twin of the cell nucleus donor.

Fasten your seat belts - things will move fast, now.

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.

Obama will fund more losing embryonic stem cell research (New Yellow Brick Award to the President)

Just days after we hear about functioning induced Pluripotent stem cells from adult skin cells, cells that can produce dopamine, the proteins missing in Parkinson's disease, we read that President Obama is going to overturn the limits on funding for embryonic stem cell research. Despite the fact that these cells match the patient because they come from the patient, that they will be cheaper, more accessible and we believe have less risk of causing cancer, this Monday morning, the 9th of March, 2009, the White House plans a quiet ceremony to sign the Executive Order.

Follow the Yellow Brick Road, Mr. President. The great embryonic Oz will get you home. Do not look behind the curtain, ignore that little man.

"Stroke of the pen, law of the land. Kinda cool!" (Thank you, Paul Begala.) We've been trying to spend a Trillion dollars every 10 days in the Obama administration. Let's just throw more good money after bad.

Typical of the news articles, is this one, from the US News and World Report, entitled (sigh)"Obama to End Stem Cell Ban Monday
Researchers applaud his action, which is expected to kick-start efforts to unlock therapeutic potential."

I recommend that you read that link above, in order to compare reality with what the proponents of destructive embryonic stem cell research believe.

The article is so full of holes. The title and first paragraph say "ban." There never was a ban. Ask Daley and Melton of Harvard who have been creating embryos for destruction to harvest the parts.

And then, there's this gem of an emotional non sequitor, I'm afraid from my State of Texas:

"It's going to remove an embarrassment for American science," said Dr. Darwin Prockop, director of the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White Hospital in Temple, said in February. "It's a statement that we're going to again believe in science."

Prockup must have been teased too much about his name as a child. Seriously, who among us stopped and now started to believe in science again?

We are not behind, we are not embarrassed, unless it's in imposing regulations. Even the "Progressives" are calling for more restrictions. The UK has more regulations on regenerative medicine and embryonic research than the US. France, Germany and Israel have similar limits on funding. Germany, at one time had criminal charges and fines attached to their ban.

CIRM has $3 Billion which must be spent on cloning and embryonic stem cell research. Their "Strategic Plan?" (This is a pdf, for a review, read this article at the CIRM website.) One cure and 2 trials in ten years. Who thinks the US is going to top their billions in embryonic research, when results with induced Stem Cells are bounding ahead?

Oh, I know, CIRM thinks the NIH should buy their $400 Million in bonds, this year. No one else wants the losing proposition.

Human cloned embryos

Oddly, there is very little notice of the confirmation that Advance Cell Technology has created cloned human embryos. Current bioethics and science reporting evidently takes the creation and destruction of human embryos for granted. In fact, the embryonic humans were created with the intention of destroying them.

No one - or almost no one - seems to notice.


Wired Science has one of the few reports that narrows in on what should be the headline:"Research Breakthrough: Human Clones May Be Genetically Viable."

It is significant that (as reported earlier) human-animal hybrid embryos do not appear to be a practical source for human embryonic stem cells. However, after reading the article itself, it appears that the story with in the story may be - I believe should be - even more significant.

The article, "Reprogramming of Human Somatic Cells Using Human and Animal Oocytes," is available online and free, here, in pdf form. Supplemental information is available here.

Lanza and his colleagues report that they used human eggs and human donor DNA to create about 50 cloned human embryos, all females. They also write that they used a human embryo started by in vitro fertilization as a "control," or material to test the validity of their other results.

Cells were removed for testing from some of the cloned human embryos and the IVF human embryo. Other than that, we do not know the fate of these embryonic human girls.

Edited January 27, 2010 to correct a "Label" typo

Human-animal embryos don't work for stem cell production

The New Scientist has a good review article that explains a new research report from Robert Lanza of Advanced Cell Technology, that attempts with "thousands" of embryos created by placing human DNA into the oocytes or eggs of animals have failed to produce stem cells. NatureNews, the news arm of the journal, Nature discusses the report, here.

The abstract of the article, "Reprogramming of Human Somatic Cells Using Human and Animal Oocytes" published in Cloning and Stem Cells, is available here. The list of researchers is very long and they are from several different laboratories.

Each of the news articles above includes statements from researchers who do not believe that human-animal cloned embryos are a dead-end for stem cell researchers. However, the confirmation of the outcome from several labs, with different researchers, is strong evidence that it is unlikely that this technique is a reasonable way to produce "patient specific" stem cells - those that are an exact match for the donor of the DNA.

I have not read the actual article, yet, but from the news articles and the abstract, it appears that the "cybrids" do express the genes of the donor DNA and are clones of the donor. However, while enucleated human oocytes are able to reprogram the DNA of the donor to result in embryos that divide to the stage at which it is possible to harvest embryonic stem cells, the emptied eggs of cows and rabbits do not. The cybrids only divide to about the 16 cell stage and do not turn on the genes responsible for pleuripotency, or "stem-cell-ness."

See my Update, written after I read the report.

Fox builds hen house

In the same set of news alerts that notified me of the Vatican's condemnation of cloning and embryonic stem cell research, I read that Insoo Hyun is the lead author of the International Society for Stem Cell Research (ISSCR) Guidelines for the Clinical Translation of Stem Cells.

The Guidelines are also published on line at Cell Stem Cell and, along with a patient handbook and other supporting material, is available at the ISSCR website. Here is the link to the page containing links to pdf of the Guidelines, patient handbook, and other materials. That page also links to the Stem Cell Cell article.

The story in the Australian blurs the differences between destructive embryonic stem cell research and the non-destructive, ethical forms such as induced pluripotent stem cell research and adult stem cell research. The focus is on the former, detailing long anticipated (but not yet begun) phase 1 embryonic stem cell research, without mentioning on-going trials or previous achievements using the non-controversial cells.

The ISSCR in general and Dr. Hyun in particular, are very much advocates of embryonic stem cell research and cloning for research. Also on his task force were Laurie Zoloth and George Daley, both strong advocates of embryonic stem cell research. Daley has worked to create embryos slated for destruction in his own Harvard lab, although he has focused on non-destructive research, recently.

Dr. Hyun has a Ph.D. in bioethics and is on the faculty at Case Western University in Cleveland, Ohio. He has focused on cloning research, and his early work included assisting the Clinton Administration's National Bioethics Advisory Committee (that would have been along with Obama transition team members, Jonathan Moreno and Robin Alta Charo) on their "secular" article on cloning. He went to South Korea with Hu Suk Wu in order to study the effects of cloning research on the Koreans - before the Korean was exposed as a fraud.

I wonder whether there was even one member of the ISSCR team who considers embryonic stem cell destruction unethical? And how soon will Dr. Hyun join his former colleagues in DC?

"Tea-bag" Adult Stem Cell Treatment for Stroke

British researchers report an amazing recovery for a 49 year old man who suffered a hemorrhagic stroke on October 15, 2008. The researchers at the company, "Biocompatibles," used adult stem cells from a healthy donor. The cells had been engineered to cause them to produce a protein that helps prevent "programmed" cell death (even after the bleeding stops and the pressure is removed) and embedded in tiny beads that had been sewn up in a cloth "tea-bag."

From the press release, published on the Medical News Today Neurology and Neuroscience website:

Stroke is one of the leading causes of death in the elderly population in the developed world. The incidence rate has been reported as 145 per 100,000. Hemorrhagic stroke is responsible for ~15 to 20% of all stroke and it is the least treatable form of stroke. It is associated with the highest morbidity and mortality rate of all stroke with only 44% of affected patients surviving the first 30 days. Only 20% of these survivors regain functional independence. The cascade of events starts with the sudden rupture of a blood vessel in the brain, causing haemorrhage and pressure inside the skull. Surgery may be used to relieve the pressure; but the haemorrhage causes a longer-term process of programmed cell death, or apoptosis, and it is this that causes the lasting neurological damage.

The CellBeads™ are delivered directly to the injury site during the surgery. They are programmed to deliver CM1, a proprietary version of a naturally occurring protein, GLP-1, which has been shown to have powerful anti-apoptotic effects. The delivery mechanism is a cluster of human adult mesenchymal stem cells obtained from a healthy donor and encapsulated in alginate beads. The cells are genetically engineered to produce the protein, which is delivered continuously, directly to the injury site. The alginate beads protect the stem cells from the body's immune system, which would otherwise destroy the foreign cells. CellBeads™ are transplanted within a retrievable mesh device and are removed completely after a treatment period of 14 days. Retrieval of the implant prevents possible long-term side effects from the transplanted cells.

The research is a "Phase I/II" trial, which means that the doctors and scientists are actually testing the safety of the treatment, and not the actual effectiveness of the treatment, itself. In other words, "does the treatment do more harm than good."

The CEO of Biocompatibles, Crispin Simon (that name is as British as tea bags), spoke to a Reuters reporter for a story published at Forbes online, stressing that the patient is young and other wise healthy, and had the standard of care for hemorrhagic strokes, surgery to relieve the pressure from the blood on the cells around the stroke. 10% to 20% of patients have similar recovery, without the Biocompatible beads.

Still, the report is a welcome source of hope for anyone who has watched and waited helplessly after a patient or a loved one had a hemorrhagic stroke.

Many Adult Stem Cell Treatments in the News

This week, we've heard about a the new "bandages" for torn knee cartilages and hope for a collagen fibers made using nanotechnology.

Animal treatments for joint disease and injury are common in horses and the treatments for dogs are now being advertised by private veterinarians in Oklahoma.

The research is ongoing in humans, too.

From the BBC, an article on the first organ regenerated from the patient's own stem cells and transplanted

Scientists in Spain have carried out the world's first tissue-engineered whole organ transplant - a windpipe - made with a patient's own stem cells.

The groundbreaking technology also means for the first time tissue transplants can be carried out without the need for anti-rejection drugs.

Five months on the patient is in perfect health, The Lancet reports.

Osiris, a company that has been developing treatments developed from adult stem cells, announced earlier this month that it is making a profit and that the rights to sell 2 treatments:

Prochymal is being evaluated in Phase III clinical trials for three indications, including acute and steroid refractory Graft versus Host Disease and also Crohn's disease, and is the only stem cell therapeutic currently designated by FDA as both an Orphan Drug and Fast Track product. Osiris also has partnered with Genzyme Corporation to develop Prochymal as a medical countermeasure to nuclear terrorism and other radiological emergencies. Furthermore, Prochymal is being developed for the repair of heart tissue following a heart attack, the protection of pancreatic islet cells in patients with type 1 diabetes, and the repair of lung tissue in patients with chronic obstructive pulmonary disease. The Company's pipeline of internally developed biologic drug candidates under evaluation also includes Chondrogen for arthritis in the knee.

(There's more on Osiris from the Washington Post, here.)


Way back in 2006, we heard about bladders grown for patients from adult stem cells and transplanted. The transplants were actually done in 1999 but the news came out about the time that Dr. Ayala was in the news for his work with Umbilical Cord stem cells.

Induced Pluripotent stem cells without viruses

"The adenovirus will infect the cells but then will clear themselves from the cells. After a few cell divisions there are no traces of the virus in the cell," Hochedlinger said. "You can't tell the virus was ever there."

Science Magazine has published a report on induced Pluripotent (iPS) stem cells from liver cells (hepatacytes) that do not show any trace of the viruses initially used to cause the regression from adult cells to embryonic-like stem cells. The report, by Hochedlinger's group at Massachusetts Gener al Hospital and Harvard, is behind a pay-wall, but there is a review here at the Washington Post.

The simple explanation is that viruses are used to carry copies of genes that turn on proteins which cause the cells to divide and produce embryonic-like stem cells. Prior research used viruses that might become permanently inserted into the DNA of the cells. These viruses did not cause an infection in the culture because the viruses used were not good at causing themselves to be reproduced or inserting themselves into neighboring cells. However, because they inserted themselves into the DNA, there was a risk that the cells could become mutated or even cause tumors due to the abnormal DNA that resulted. In the case of Hochedlinger's cells, the adenovirus used does not insert into the DNA nearly as often, and when it does, the cell is able to repair the DNA in subsequent copies of the DNA as it reproduces the nucleus of the cell in order to divide to become two cells.

The cells are infected, they change because of the infection, but their granddaughters are able to get rid of the infection, while continuing to act like embryonic stem cells instead of grown up liver cells. The new "adeno-iPS" cells pass all the tests for "stemness."

Just think, no need for egg cells, no cloning, no destruction of embryos, and we're one step closer to healing within the body - to learning how to heal without transplant rejection or tumors due to the treatment. One day, we may be able to regenerate organs and tissues in place, as needed.

Human-pig embryo approved in UK

The "cybrid" or hybrid human-animal embryos are created in the laboratory by Somatic Cell Nuclear Transplantation, using emptied eggs from animals and the nuclear and cellular DNA from humans.. We know that there are currently experiments on-going with the human embryos made using emptied cow eggs (more on the "ease" of making these embryos, here), and now the British have authorized the development of pig-human embryos.

The experimenters admit that the problem will be achieving embryos and embryonic stem cells that do not contain DNA left from the egg. Proving the purity and "human-ness" of the stem cells will be a complication that I do not believe they will be able to overcome, at least for transplantation into humans, except possibly in the case of severe, last-hope disease and trauma.

The ethical debates about xeno-transplants and treatments using living organs, cells and tissues from animals carry the risks of transmitting animal diseases that humans have no immunity for and the development of new strains of disease that cross species lines. Ethicists have predicted that at least the early patients will have to live their lives in isolation at the worst, and have life-long surveillance at the best. (more on the debate, here and here.)

However, the researchers will probably be able to develop other uses, such as the early warning chemical weapon detection systems that are being developed by our own military, using human embryonic stem cells.

Rather than humanitarian and medical hope, I believe that time will show us that the research is the result of pure greed, with each lab hoping to come up with a product that can be patented and sold. I'm disappointed that the courts and "ethics" bodies in the US and UK have allowed these patents of human organisms. The drive to "create" new human cells and artifacts using human DNA is the logical outcome.

Yamanaka has a conscience

“When I saw the embryo, I suddenly realized there was such a small difference between it and my daughters,” said Dr. Yamanaka.

The New York Times article on Shinya Yamanaka, "Risk taking is in his genes," (free one time registration necessary) should get the headline-writer in trouble for a sad pun.

Instead, Dr. Yamanaka might be in trouble with the objectors to conscience. (No links, just look at today's posts - or the last two months of posts - the subject keeps popping up.)

People like John Gearhart, MD will want to "put pressure" on Yamanaka to write letters to Nancy Pelossi and the rest of the US legislators making the usual reactionary case for Federal funding for embryonic stem cell research in light of the successes with non-destructive research.

The NYT reporter, Martin Fackler, can't be too popular in the next few days for pointing out that the US laws and funding are not nearly as tight as those in Japan, due to moral objections in that country:

In 1999, his career got a break when he was hired by other universities, including Kyoto University in 2004, that were willing to give him a laboratory and more money. At about the same time, he said, he visited his friend’s fertility clinic. That visit inspired him to find a way around the moral issues that had bogged down stem cell research, not just in the United States but also Japan, where the Education Ministry put tough restrictions on embryo use.

In fact, restrictions are so tight that he says he cannot use human embryos at his laboratories here. Instead, research using human embryos is done at U.C. San Francisco, where he maintains a small two-person laboratory. He said he had never handled actual embryonic cells himself, and the American lab uses them only to verify that the reprogrammed adult cells are behaving as true stem cells.

“There is no way now to get around some use of embryos,” he said. “But my goal is to avoid using them.”

For a look at the science and bioethics slant on these revelations, see Wired Science (see the comments on this one), Blog.bioethics.net, Wesley Smith's Secondhand Smoke, and Jennifer Lahl's blog, "The Human Future."

Wait 'Till Next Week! (More iPS good news)

Dr. Yamanaka of Japan, the MD who made history last week by announcing that he had been able to obtain embryo-like stem cells fom adult skin cells called fibrobalsts. On Friday, November 30, has published a new report in Nature Biotechnology telling us how he was able to skip inserting the potential cancer causing gene, c-Myc.

At this rate, who knows what we'll have next week?

From The Scientist (online here):

In the current study, the researchers showed that pluripotent cells can be made from both mouse and human adult cells without introducing the c-Myc gene, by transducing just the other three. It's not that Myc isn't needed in the process, the authors noted in the paper; rather, they suggest that the other three genes may be spurring endogenous Myc activity. None of the 26 chimeras made from cells generated without c-Myc developed tumors within 100 days, compared to six out of 36 chimeras made from cells using all four genes.
*************
So far, too, efficiency with this triple-gene method is much lower than with the original four genes; half of the experiments without c-Myc did not produce pluripotent cells at all, while experiments using the four genes almost always yielded pluripotent colonies. "Does this mean that it now only works with a rare cell type?" Lovell-Badge wrote. "As always, many more questions are posed than answered."

The question is whether all fibroblasts are alike, or whether there is a smaller group of fibroblasts that are easier to induce to become "induced Pluripotent Stem" Cells.

If there are specialized cells in the skin that are easier to manipulate than others, this is good news for researchers and the patients who are looking toward stem cell research for treatments and cures.

Translation of Yamanaka, Yu "induced Pluripotent Stem Cells" (Revised)

Scientists who report their findings are expected to discuss the problems as well as the outcome of their research. This is usually found in the "Discussion," "Conclusions" or "Results" section of the paper. This is the best place to figure out what the researches intended, what they did and what the report means. (Then you go back and check to see if they proved what they "discussed." And then, you wait for other labs to confirm it.)

The actual (Takahashi et al., "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors," Cell (2007).) Cell article on reprogrammed adult fibroblast skin cells, the "induced Pluripotent Stem Cells) or "iPS," is available for free, here. The Science Magazine report about similar work by James Thomson from Wisconsin (the researcher who reported the production of human embryonic stem cells in the first place) is supposed to be published November 22, 2007. (Editorial note 11/30/07 – Science published the Thompson and Yu report the same day that Tamanaka's report was published, two days ahead of schedule. See my “translation,” here.)

To the best of my understanding, here's a translation into layman's terms about what the Takahashi/Yamaka report means:

While it took a lot of cells and more time than the researchers first expected because the human iPS grew much slower than the mouse iPS,

1. The cells that grew looked and functioned like human embryonic stem cells with a few minor differences,
2. They believe they proved that their technique is responsible for all the new pluripotent cells that were found in their cultures(there weren't any cells from another culture introduced accidentally or on purpose and which would make them look more successful than they were),
3. The cells could be directed to develop nerve cells and heart cells,
4. They were able to use several types of adult specialized cells to achieve iPS, and
5. The researchers suggest several possible ways to overcome the drawbacks of the process.

The authors believe that the inefficiency or the need to begin with lots of adult cells and wait a little longer for a substantial amount of human iPS should not be a "practical" problem because the adult cells are easy to obtain and labs all over the world should be able to reproduce their results. Since the technique should be well-funded (it qualifies for US Federal funding and is ethical, since no human beings have to die), the authors believe it will be possible for lots of researchers to work on them.

If I were to predict the future, I would anticipate banks of iPS - or even specialized or intermediate forms of cells that are produced from iPS - being stored for each of us, just in case. In the very long term, we will learn more about stimulating our on bodies' stem cells from research on these cells, so that we can repair or prevent damage without transplants or waiting for cultures to grow in the lab.

The major hurdle is that the cells were produced by the Recombinant DNA technique, using retroviruses in plasmids.

The retroviruses are a class of viruses that actually insert themselves into the DNA strands of animal or plant cells to become a part of that cell’s DNA and are copied when the cell reproduces. They are manufactured in the lab in the form of plasmids in order to carry genes into the experimental cells.

Plasmids are little bits of DNA, a mini-virus in a circle. Think of a chain with pairs of magnets or interlocking puzzle pieces that connect the ends and make a loop. When open, the plasmid becomes a strand of DNA which has ends that are "sticky.” When placed in a culture with mouse or human cells, the plasmids infect the cells and then move into the nuclei of the cells. The retroviral DNA is inserted or inserts itself into the DNA of the host cell because the sticky ends of the plasmid strand match or mate to certain areas of the host DNA.

Plasmids can be manufactured to carry copies of genes that researchers want to insert into the DNA of experimental cells. The technique is common in commercial and experimental labs for at least the last 30 years. In fact, "Recombinant DNA" is used to induce strains of bacteria and yeast cells in cultures to manufacture vaccines like the flu and Hepatitis B vaccine and the insulin used by diabetics these days. The particular retroviruses used by Tamanaka are said to be "strongly silenced in humans." In other words, they don't normally get reproduced as viruses when the cell divides. Once they are taken up in the cell DNA, the viruses used in research don't break out to become infectious viruses, again. However, some of them can induce the cells to form tumors or cancers if injected in an animal or human.


One of the possible problems that the article notes is that the new iPS cells each had several copies of the retrovirus included in their DNA. There is a concern that these bits may be responsible for the tumors that were seen in the mice used in the experiments. Before iPS can be used in humans, it will be necessary to learn to remove all the viral particles or to learn to make the cells without viruses that can cause tumors. Otherwise, there is a risk of causing cancer in patients.

The researchers note that another group of scientists have already reported that it is possible to insert one of the genes without using retroviruses and that the hope is to either find a way to insert the other three genes or to remove all traces of the virus.

There's also a suggestion that what they are actually inducing to grow is a sub-set of fibroblasts with the tendency to become embryonic-like stem cells.

"Fertilized eggs" and cloned human embryos (The future, again)

"ScienceBlogs" is one of the examples I give when I'm trying to explain the anti-life, anti-religion atmosphere that is pushed (like a religion itself) in our universities and by the Powers That Be in science academia and publishing. I think I may have identified one or two of the bloggers as believers (proof that miracles happen?), but no one identifies as pro-life or even respectful of us.

Normally, the community in the 66 blogs over at "ScienceBlogs" talk to each other, but I read them to see what's going on. Since I have a tendency to tilt at windmills, occasionally I post. The gang over there is so unhappy with the breakthrough on embryonic like stem cells from adult stem cells that it's almost like reading up on the Clintons at one of the Pink or websites. (Watch out for the language.)

I posted a reply to the atheist blogger (look for the "Red A" banner suggested by Richard Dawkins), PZMyers, who wrote some silliness at his blog, "Pharyngula" today. (I ignored the nonsensical non sequitur that the President hadn't shown any interest in alternative fuel - I can remember months of jokes about the saw grass and there's a Kennedy blocking the wind farms on the East Coast, for Pete's sake.) But I did point out that there's been no impediment (other than in the funding of Ph.D. candidates who moan about staying up 'till 2 AM - standard for pre-meds and interns in the old days) because of the Bush administration policy on stem cell research.

One poster replied with 500 words to convince me that "fertilized eggs" do not have any moral standing, cloned human embryos would not be cloned humans and that reprogrammed, mesenchymal or any of the other ethical stem cells do not have the promise that embryonic stem cells do. Along with the problem of how long it takes to direct embryonic stem cells.

First, an egg ceases to be an egg when it's fertilized. At that point, it's an embryo.

Second, the poster is not keeping up. The mainstream press and science publishers no longer argue that somatic cell nuclear transfer doesn't result in an cloned embryonic primate or human.

Third, again, you've got to keep up: James Thomson has said that the reprogrammed cells, "are probably more clinically relevant than embryonic stem cells," he explains. "Immune rejection should not be a problem using these cells.""

In the near future, the treatments will come from stem cells and precursor cells - it probably won't be necessary to start at the embryonic stem cell or pluripotent stem cell stage. While each line of multipotent adult stem cells is more limited than the ideal embryonic stem cell line, there are many kinds of multipotent lines. I expect the lessons we learn from the Yamanaka and Thomson techniques to be used to begin at these more differentiated cells, which can be directed faster and easier than the pluripotent cells, with their innate pathonemnonic tendency to form tumors.

In the long run, we hope to prove John Gearhart right: he's been on record for 5 (Washington Fax, November, 2002) years that, "Stem cells won't be used as therapies, but will spawn them."

Just as we use stimulating factors to encourage the production of blood cells, rather than transfusing as often as we once did, the plan is to learn to turn the necessary genes on to produce the specific transcription factors that will stimulate stem cells. We'll learn about "tropic factors" like the brain-derived neurotropic factor that seems to regulate the development of nerve cells and nerve repair.


5 years ago, we hadn't found all the stem cells and precursors that we know about, now. We didn't realize that women continue to make oocytes after birth, that there are neuron stem cells and precursors, that we can make functional liver tissue masses from umbilical cord blood. We certainly didn't know as much as we do - and how little we know - about Oct4 and the other regulatory homeodomains. We didn't understand about niches and the vital role of the physical environment and conditions beyond those chemicals.

The poster does use one of my favorite phrases, however: "We stand on the shoulders of giants." He forgets that that will be true for our children of the future, also.

Translating Thomson’s “Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells”

Yu, Thomson, and all, from Wisconsin published their paper on reprogrammed induced Pluripotent Stem (iPS) cells from adult cells online in Science Express online, yesterday, just after the Yamanaka/Takahashi team from Japan published theirs in the journal, Cell. (The Thomson paper was not scheduled to go live online until the 22nd.)

As discussed on this blog, yesterday, Yamanaka’s group built on their earlier research published in 2006 and 2007, using mouse fibroblasts to prove that four genes, Oct4, Sox2, c-myc, and Klf4, could reprogram those cells to a state that resembled embryonic stem cells in all tests that they tried. Then, they used fibroblasts from commercially available samples from 1) a skin biopsy taken from the face of a 36 year-old Caucasian woman, 2) synovial cells (joint lining) from a 69 year old Caucasian male, and 3) neonate foreskin skin fibroblasts.

(This last is a common source of skin fibroblasts, with easily and ethically accessed skin tissue, collected at the circumcision of newborn boys.)

The Thomson team did not begin the basic research using mouse cells and did not simply go forward using the genes from the earlier experiments on mouse cells. Instead, they started at the beginning, using human Embryonic Stem Cells (hESC) that had been directed to become a special type of white blood cell, CD45+. This type of cell can be manipulated to demonstrate whether they had the functioning gene, Oct4 (a definite marker that is used to prove whether or not a cell is a hESC), by growing them in the presence of gentamycin, an antibacterial.

By adding some genes and removing others, the team determined that they had, “identified a core set of 4 genes, OCT4, SOX2, NANOG, and LIN28, that were capable of reprogramming human ES cell-derived somatic cells.” They also discovered that the cells could be reprogrammed into embryonic-like cells without Nanog, but that Nanog made it possible to recover more reprogrammed cells.

(From the text accompanying Fig.1: "In three independent experiments using different preparations of
mesenchymal cells, individual removal of either OCT4 or SOX2 from reprogramming combinations eliminated the appearance of reprogrammed clones, whereas the individual removal of either NANOG or LIN28 reduced the number of reprogrammed clones, but did not eliminate such clones entirely.")

Next, they tested this combination of genes in a commercially available, genetically modified cell culture, IMR90 fetal fibroblasts. (These cells were cultured from a little girl aborted at 16 weeks gestation. ) These cells are fetal cells, not adult cells, and they were chosen because they have been studied and the genome is well known. They do not grow well in the fluids and conditions that encourage cultures of hESCs and the researchers could identify them by the way that they look.

Next, in order to prove that the genes could reprogram “adult cells,” the team used fibroblast cultures from foreskins to produce 4 different cultures of reprogrammed induced Pluripotent Stem Cells.

The authors conclude,

"The human iPS cells described here meet the defining criteria we originally proposed for human ES cells, with the significant exception that the iPS cells are not derived from embryos. Similar to human ES cells, human iPS cells should prove useful for studying the development and function of human tissues, for discovering and testing new drugs, and for transplantation medicine."

Edited typos 11/21/07 17:30 PM (That could be the next neuroscience break through: why don't we see our typos until later?)

"I want" ethics reigns, even with good stem cell news

I found someone willing to admit that she's not happy with today's news on the production of embryo-like stem cells without the destruction of embryos or harm to women from donating eggs.

Robin Alta Charo is a lawyer who, as part of the Clinton administration's National Bioethics Advisory Commission, helped fabricate the policy to allow research on embryonic stem cells if the embryos were killed using someone else's money. She's part of the surprisingly small community that pushes for cloning, embryo destruction and Federal funding of the research, as well as attempting to regulate the very institutions, boards, and corporations they oversee. (See my article "Ethicists for hire?" for more on the relationships. Or, simply Google "R. Alta Charo" - for some reason she drops the "Robin.")

Charo is on record as hoping that cloning and regenerative medicine will finally prove that we humans aren't anything special, and maybe even that there's no God. If you think I'm exaggerating, listen to the lecture recording available, here.)


Anyway, the Science and Cell reports on research that produces cells that appear indistinguishable from embryonic stem cells that were published online today, are not the best of news to Ms. Charo.

From the ScienceDaily excerpt of the University of Wisconsin press release, with the cute title, "Reprogramming the Debate: Stem Cell Finding Alters Ethical Controversy,"

"It's going to fuel those who call for preferential federal funding only for non-embryonic stem cell research and it will certainly complicate any efforts to expand funding for embryonic stem cell research at the federal level," she says.
. . .
"Any piece of research like this that suggests that we can get cell lines that are equally usable without having to go through an embryo in intermediate steps is going to undermine any effort on the part of Congress to overturn the Bush policy," she says.

"No matter how well this new technique can be used for many of the disease-research and disease-treatment applications foreseen for embryonic stem cell and cloning research, however, calls for criminalization or wholesale de-funding of embryonic stem cell and cloning research are not warranted," Charo adds. "Criminalizing any area of science, as opposed to merely regulating it, would be contrary to the political and constitutional traditions of academic and scientific freedom, as well as the historical spirit of inquiry that characterizes this country."

From the Wisconsin article linked above,

Charo serves on several expert advisory boards of organizations with an interest in stem cell research, including CuresNow, the Juvenile Diabetes Research Foundation, the International Society for Stem Cell Research and WiCell, as well as on the advisory board to the Wisconsin Stem Cell Research Program.

In 2005, she was appointed to the ethics standards working group of the California Institute for Regenerative Medicine. Also in 2005, she helped to draft the National Academies' Guidelines for Embryonic Stem Cell Research, and in 2006 she was appointed to co-chair the National Academies' Human Embryonic Stem Cell Research Advisory Committee.

I'm sure that we shouldn't assume that those connections with Wi-Cell, the California Institute for Regenerative Medicine, or even her associations with the Alan Guttmacher Institute and Planned Parenthood have anything to do with her dislike for what many consider good news. And ignore the comments about the "Bush Administration." Charo's involvement with the Progressive Bioethics movement, couldn't have anything to do with politics.

Embryonic Stem Cells from Patient's Own Adult Stem Cells

Well, they did it!

From Reuter's, UK:

WASHINGTON (Reuters) - Two separate teams of researchers announced on Tuesday they had transformed ordinary skin cells into batches of cells that look and act like embryonic stem cells -- but without using cloning technology and without making embryos.

Their breakthroughs could make possible the long-sought goal of tailor-made medicine, but without the political, scientific and ethical roadblock of using human embryos.

Both teams call the new cells induced pluripotent stem cells and say they look and act like embryonic stem cells -- the master cells that give rise to every cell and tissue in the body.

. . .

James Thomson of the University of Wisconsin in Madison and colleagues reported their finding in the journal Science while Shinya Yamanaka of Kyoto University in Japan and colleagues reported theirs in the journal Cell.

I haven't read either article, so -- long pause ---

Dolly's Dad: Cloning, embryos and eggs not needed

10 years after the world learned about the cloning of Dolly the sheep, the scientist responsible for her birth announces that cloning is passe'.

Just after the announcement that a US lab has managed the first confirmed cloning of primate (monkeys, not human) embryos using adult cell donor DNA, Ian Wilmut made statements to the UK press that he's abandoning the cloning track for research using something like Japan's Yamanaka's process of dedifferentiation or reprogrammed adult cells to produce stem cells. (He's also selling the paperback version of his latest book.)

This approach, he says, represents, the future for stem cell research, rather than the nuclear transfer method that his large team used more than a decade ago at the Roslin Institute, near Edinburgh, to create Dolly.

Last year, at the American Society of Bioethics and Humanities Conference, the top ‘ethicists’ were nearly in a panic over these techniques. They evidently put pressure on Yamanaka to and criticize his own research. Then, 3 other labs proofed the technique and the Yamanaka’s lab advanced a step or two. Gearhart and Moreno were still scoffing last month, when they spoke at the National Academies of Sciences museum during the ASBH conference.


I’m afraid that too many labs and too many PhD candidates and sponsors have all their eggs in the cloning basket for the issue to fade decently. Talk about being left behind — all US research centers, such as the California Institute of Regenerative Medicine — will be negated if they insist on following the dead end trail of cloning and unethical destructive embryonic stem cell research.

The Yamanaka technique involves reprogramming adult fibroblasts - skin precursors - to a primitive, embryonic stem cell state. The stem cells are not quite 'totipotent" from what we can tell -- they aren't capable of forming new embryos. But they are capable of forming "all the cells of the body," at least with manipulation in the proper environment.

We're going to hear more and more dispute about the "proper" name for the cells -- disputes over whether they are actually stem cells. And a huge amount of discussion about the dangers from the viral transfection that is used to add the genes that turn on stemness.


We will be expected to forget that

1. No one has been able to clone a human embryo in spite of thousands of eggs used in Hwang's scam alone,

2. That 13,000 monkey eggs were used in the latest attempt to clone primates, that the published study relates an efficiency of 0.7% success, and the authors aren't quite sure why they were successful where other labs weren't,

3. The fact that true embryonic stem cells are short lived in the body and difficult to control (reports actually criticized the embryonic like stem cells from dedifferentiation for making tumors in mice - although that is one of the properties that defines embryonic stem cells)

4. That transfection with plasmids and specialized virus particles is an established technique of gene therapy,

5. and that the production of stem cell lines toward the end-stage adult cells has used viral transfection as well.

Even though he spouts the proper mumbo jumbo about the "moral status of the human embryo" (and that a person is someone capable of valuing herself - with the gradual acquisition and loss connected with functional capability), don't be surprised if Wilmut is, himself, negated and Watsoned because of his disloyalty to the cloning and embryo-destructive catechism. (James Watson's non-PC comments from last month cost him his lab, although he's been saying the same things for years.)


Now, if only the US, and especially the Texas, research Powers That Be will pay attention and learn.

A brief history of cloning

Steve Connor of the The Independent, from Britain, tells us the history of cloning.

But first, the "good news:"

A technical breakthrough has enabled scientists to create for the first time dozens of cloned embryos from adult monkeys, raising the prospect of the same procedure being used to make cloned human embryos.

Attempts to clone human embryos for research have been dogged by technical problems and controversies over fraudulent research and questionable ethics. But the new technique promises to revolutionise the efficiency by which scientists can turn human eggs into cloned embryos.

It is the first time that scientists have been able to create viable cloned embryos from an adult primate – in this case a 10-year-old male rhesus macaque monkey – and they are scheduled to report their findings later this month.

The scientists will also demonstrate that they have been able to extract stem cells from some of the cloned embryos and that they have managed to encourage these embryonic cells to develop in the laboratory into mature heart cells and brain neurons.

Scientists who know of the research said it was the breakthrough that they had all been waiting for because, until now, there was a growing feeling that there might be some insuperable barrier to creating cloned embryos from adult primates – including humans.
*****

The Oregon team, working with a group in China, has so far produced about 100 cloned embryos that have been transferred into around 50 female macaques, but none has resulted in a full-term pregnancy, he said.

"It's possible that we're still just having bad luck. We're producing may be one in 20 or one in 30 cloned blastocysts that are 'normal' and capable of producing a pregnancy and we just haven't got them into the animal recipient at the right time to allow implantation and pregnancy to occur," Professor Wolf said.

"The focus now is going to be on therapeutic cloning and using the non-human primate as a paradigm for therapeutic cloning for what you might be able to do clinically," he said.

"We're the first to do it, although it's a tainted subject because of the fraudulent research that came out of South Korea. One can never be sure but there may be some validity to what the South Koreans did. But this would now be the first documented therapeutic cloning in a primate," he added.

A brief history of cloning

The monkey-cloning technique is the same basic procedure that resulted in Dolly the sheep. The nucleus of a healthy, unfertilised egg is removed and another nucleus from the mature skin cell of an adult animal is placed inside the egg. With careful timing and the use of electrical pulses, an embryo can be created which is a genetic clone of the skin tissue donor. It is possible to implant embryos created in this way into the womb to produce cloned animals. This so-called 'reproductive cloning' of humans is illegal in Britain and many other countries. However it has been applied to a range of animal species, including:

* Cow: Many domestic cattle have been successfully cloned. First attempt to clone an endangered species was Noah, a rare gaur ox, which was cloned in the US in 2001 but died 48 hours after birth

* Mouse: Cumulina was a common brown house mouse, cloned from adult cells at the University of Hawaii in 1997. She survived to adulthood and produced two litters, before dying in May 2000

* Horse: Called Prometea, the first cloned horse, born in Italy in May 2003

* Cat: A kitten called CopyCat was born in 2002 in Texas, and gave birth to three kittens by a natural father in September 2006

* Dog: Snuppy, born in South Korea. Doubts about its authenticity were dispelled by DNA tests. The group has also cloned two wolf cubs, called Snuwolf and Snuwolffy using the same procedure. Cloned Afghan hounds named Bona, Peace and Hope have also been born.

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!

New President of California Stem Cell Institute

Alan Trounson, PhD, the researcher responsible for the first in vitro (IVF) birth in Australia, who once had to apologize for misleading the Australian Parliament after showing them a video that he claimed showed a mouse that walked after human embryonic stem cell treatment for spinal cord injury (in fact, they were fetal cells from aborted babies), and the man who was recently hired as President of the California Institute of Regenerative Medicine is not under investigation . But the people at his last project are, for discrepancies in reporting at his old lung regeneration project.

The $1 Million (Australian) grant required reports on progress each 3 months. It seems that there were questions not only about the lack of results in the project, but doubts about whether someone falsified one of the reports.

The Herald Sun, "Australia's largest newspaper," reported on October 13th that

World-renowned Melbourne scientist Alan Trounson's $1m stem cell research project is under investigation after it was scrapped for delivering highly doubtful results.

Monash University is examining anomalies in interim findings from the lung regeneration research conducted in its labs with public money.

Prof Trounson -- a doctor of philosophy who was headhunted to run the world's richest stem cell outfit in the US next year -- was the project's principal investigator.

The research was done by a team of about 13 scientists, including postgraduate students, to see how stem cells might help slow lung disease in cystic fibrosis sufferers.

It was stopped in February when the Australian Stem Cell Centre cut funding after a three-week investigation found inconsistencies in multiple progress reports.

The Herald Sun has learned the reports were signed by Prof Trounson and a senior researcher.

Another investigator in the lab is the main focus of the investigation, however. (Warning to all Ph.D. candidates - and you thought it was dangerous enough when choosing your sponsor.)

As of 10 PM CDT, there's no reports in US news sources.

Rao: Adult Stem Cells "soon to be on the market"

The journal Stem Cells has published an Open-Access review by the former NIH director, Mahendra Rao, MD, PhD, covering last month's "Adult Mesenchymal Stem Cells in Regenerative Medicine Conference" at the National Center for Regenerative Medicine in Ohio.

Another review with summaries of some of the individual talks as well as the history of the National Institute for Regenerative Medicine and Dr. Arnold Caplan's part in founding both the NIRM and Osiris, can be found at Medscape.

Mesenchymal stem cells (MSCs) can be found in bone marrow and other organs. MSCs are proving to be multipotent, meaning that they can be induced to give rise to different types of cells.


Speakers at the conference included virtually every "big" name in stem cell research, including Dr. Rao, Caplan, Anthony Atala, Catherine Verfaille, and Paul Simmons. The program covered the history, basic science and techniques involved in harvesting and culturing mesenchymal stem cells. There were reports covering the multipotent nature of MSC's and some of the treatments and commercial applications that are in use or will soon be available. One company, Osiris, has been in phase III of some clinical trials of stem cells for treatment of heart disease, graft vs. host disease, Crohn's, and cartilage and tendon repair. Veterinarians are already using MSC's to treat horses and other animals.

Take a look at the last page of the review which contains a graphic covering the wide range of topics.

Stem Cells in Tendons (Plus some education)

The National Institutes of Health (NIH) reported last week that scientists have isolated stem cells from tendons which help in the growth and repair of those structures. The abstract of the peer-reviewed report, "Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche," is curently available at Nature Medicine at Advance Online Publication. (Later readers of this post will need to search at Nature Medicine for updated location.)

Once again, we have confirmation that tissues that grow, remodel and repair themselves after birth have stem cells that are available for research and which may soon be harvested from injured patients and utilized in medical treatments.

From "Monsters and Critics,"

Songtao Shi identified unique cells within the adult tendon that have stem-cell characteristics -- including the ability to proliferate and self-renew.

The researchers were able to isolate the cells and regenerate tendon-like tissue in an animal model.

'Clinically, tendon injury is a difficult one to treat, not only for athletes, but for patients who suffer from tendinopathy such as tendon rupture or ectopic ossification,' Shi said. 'This research demonstrates that we can use stem cells to repair tendons. We now know how to collect them from tissue and how to control their formation into tendon cells.'

The NIH press release is the most interesting to me (probably because I haven't had a sprained ankle in a while), because of the discussion of "niches" and the conclusion of one of the authors to "follow the phenotype." (More on this phrase, later.)

From the NIH press release:

Marian Young, Ph.D., an NIDCR scientist and the senior author on the study, said the findings also bring to light an unexpected biochemical habitat, or niche, that harbors stem cells. The cells are embedded between layers of extracellular matrix (ECM), the chain-like coils of protein that give tendon its elasticity and contain relatively few cells or blood vessels. To date, most known adult stem cells occupy cell-rich environments with a ready source of nutrients.

"We read a lot about the promise of stem cells, but sometimes overlooked is the importance of the niches that surround them," said Young. "Each individual niche in the body helps to carefully regulate the activities of a given stem cell. What�s nice is we have begun to characterize both in tandem, and that gives the field a head start in learning to meld an understanding of both and hopefully one day to re-engineer damaged tendon."

According to Young, the stem cells, which her group named tendon stem/progenitor cells, or TSPCs, would have never been discovered had it not been for their studies with mice — and good fortune. Young�s laboratory for several years had been knocking out, or inactivating, specific genes in developing mice that likely were involved in forming skeleton and its associated tissues. Among these genes were those that encoded the structural proteins biglycan and fibromodulin, major components of the ECM.

Having knocked out the genes for biglycan and fibromodulin in a new litter of mouse pups, they noticed the mice developed an unusual gait and had difficulty flexing their limbs at two months old. Subsequent X-rays provided the reason: Without biglycan and fibromodulin, the mice were abnormally forming bones within their tendons.

Young and her colleagues theorized that the tendons in these mice might contain stem cells that normally form tendon and, when their niche is altered, misguidedly create bone. If so, they theorized the ECM might house the stem cells, and biglycan and fibromodulin likely played a key role in regulating their normal activity.

The article goes on to quote Dr. Young as saying, "The lesson here is: Follow the phenotype."

If I understand correctly, Dr. Young is confirming that in order to produce stem cells and progenitor cells that will be useful and therapeutic in human patients, we will need to understand and/or be able to reproduce or influence the actual environment where the stem cells develop. Rather than focusing so much of our research efforts and money on embryos, we should be looking at the normal and abnormal local conditions that we want to treat: the "extracellular matix," the local chemical, hormonal, and physical conditions which surround the body's own stem cells and which may be tweaked to induce healing in place, in the patient.

Patients' own adult stem cells in the news

There's hope in the news for future adult stem cell therapies using patients' own stem cells within the next ten years.

The (UK) Times Online reports on the rapid progress in research on tissue regeneration using patients' own adult stem cells to produce heart valves and muscles. The researcher predicts the technology will be available in three to five years for use in humans.

To support this hope, Nature Biotechnology will publish a report on adult stem cells that make muscles in immune deficient mice. The abstract is available here and the UPI report is available here.

CIRM: Another one bites the dust

They just can't get good help - a scientist is leaving, just after the resignation of the temporary president of the California Institute of Regenerative Medicine. Could it be that everyone who works for CIRM sees failure down the road?

From this week's Bioedge 263, a weekly newsletter on biotechnology out of Australia:

CALIFORNIA STEM CELL INSTITUTE SHAKEN BY RESIGNATION

Like Gulliver, the California Institute for Regenerative Medicine, has been pinned down by countless pygmies equipped with lawsuits. The lengthy delay in launching its ambitious US$3 billion research program, with a focus on embryonic stem cells, appears to be taking its toll. Its president, Zach Hall, resigned in April, and now its chief scientist, Arlene Chiu, has announced that she will be leaving. Several other executives have also left in recent months.

Wired.com bloggers are talking about the difficulty of finding a permanent president, after years of fignting litigation over the funding passed by the California voters:

Insiders suspect Chiu's resignation is at least partly related to frustration over the difficulty the agency has had in finding a permanent president. After an unsuccessful seven-month search for a permanent replacement for former president Zach Hall, CIRM hired Richard Murphy as interim president earlier this month.

UPDATE: Dale Carson, the communications director at CIRM just sent a statement from Zach Hall that makes it even more clear what a big loss Chiu is:

Persuading Dr. Arlene Chiu to come to CIRM from NIH was one of the most important accomplishments of my presidency. As the senior CIRM scientist during its first three years - a time of constrained resources, Arlene recruited, mentored and led the scientific team responsible for awarding the first $200 M in grants for stem cell research in California - a remarkable legacy. She has a deep understanding of stem cell research, expert knowledge of grants administration, and extraordinary personal qualities of integrity, grace and a passion for the mission of CIRM. Arlene has left her mark on the DNA of CIRM. She will be hard to replace.

-- 

Great news from the mom of a child with diabetes (cord blood)

There's a great comment today from the mom of a boy whose Type 1 or Juvenile Diabetes is being treated with cord blood:

Darla Lindenmayer said...

My son so far has been the oldest to participate in the cord blood trial. We are excited how well it is working. My son has gone from 5 shots a day to only one and that one is being weaned down. It also has cured him of his thyroid disease which he also was diagnosed with a few months after he was diagnosed with juvenile diabetes. We know the cord blood we collected is working somehow to change the molecular structure and increase his beta cell production. We hope and pray that this continues on. Dr. Haller is doing great research!!

Diabetes and thyroid disease tends to go together - more evidence for an autoimmune risk factor for Diabetes.

Thanks, Ms. Lindenmayer for giving us the update!

Angina treatment from patients' own adult stem cells

Patients were given shots to stimulate the production of blood stem cells, the cells were removed from their blood - not from a bone marrow biopsy - and then injected in areas of their hearts that were alive, but not functioning.
There's more information at ScienceDaily online.
While the researchers remind us that this is a "small pilot study," I'll bet the patients who went from having chest pain when walking across the room to being able to climb stairs don't feel that it was so small!

The Veto vs. the Big Picture

Yesterday, the President vetoed a Bill that would have "enhanced" some human embryos right out of life, while pledging to save more lives, now.

According to the White House Press Release reporting on President Bush's speech, he was joined by Dr. William Hurlbut and Dr. Don Landry. Both of these men are proponents of alternative means to harvest cells that could be as "plastic" as embyronic stem cells - in fact could be embryonic stem cells - without destroying or harming embryonic humans.

The President got his priorities right as well as his science.

Congress has sent me a bill that would overturn this policy. If this legislation became law, it would compel American taxpayers -- for the first time in our history -- to support the deliberate destruction of human embryos. I made it clear to Congress and to the American people that I will not allow our nation to cross this moral line. Last year, Congress passed a similar bill -- I kept my promise by vetoing it. And today I'm keeping my word again: I am vetoing the bill that Congress has sent. (Applause.)

Destroying human life in the hopes of saving human life is not ethical -- and it is not the only option before us.

First, he states that no matter how "useful" the harvest of human embryos, it is not ethical and he will not support the purposeful destruction of some non-threatening humans for the benefit of others.

We call these humans "innocent,"but this is one of the words that will be attacked when the opposition reports on the story. When you hear or read about someone ridiculing the notion that the President is protecting "innocent" embryos, you could ask them how any embryo ever harmed them enough to deserve to die.

It might also be useful to remember that there was protest in the '70's over the institution of in vitro fertilization and the creation of human embryos out side of the body. We were promised that these youngest members of our family would only be loved, wanted and implanted, never used as experimental fodder.

Well, that promise lasted about as long as the promise to use only "left over" embryos, a promise broken at Universities around the US, at least very remotely supported by our taxes and society.

This week, we've seen an increased push for that Country's regulatory board to allow human-animal hybrid embryos, using human DNA and animal eggs. We've heard about one researcher's cloning of Primates using rhesus monkey skin cells in order to successfully create embryos, and then to destroy and harvest two lines of embryonic stem cells. (Note, everyone's calling it "cloning," although watch the way the topic is quickly moved to "blastocyst" from embryo.) There'll be quite a bit of hype about how this will advance human cloning. There's even a new report that indicates that 60% of IVF parents would donate their embryonic children to research if they knew the embryos would be used to harvest stem cells.

Please watch the language and the route of the discussion. We'll hear about the "waste" of embryos that are left over, but no suggestions that we make fewer embryos. Instead, immediately following, there'll be a plea for funding to create more, specific embryos in order to study disease. Disease which is not seen at the embryonic stage of life, by the way. we'll hear about the "necessity" for "patient specific stem cells," using "SCNT" (yes, it's cloning, see the articles on the cloned rhesus monkeys) to create new blastocysts and new cell lines to match each patient and each disease. You'll probably read the new term, "blastocystic" or "blastocyst" stem cells, being touted by at least one author.

Men have always killed each other and they probably always will. There's just no need to hand them US Federal tax dollars for doing so.

Non-destructive embryonic stem cells

It's all over the web (here and here, at the "news@nature.com" site,for instance), three separate labs have been able to reproduce embryonic stem cells by "reprogramming" adult cells from skin.

Much of the commentary is like Art Caplan's comments quoted in the first (Blog.bioethics.net) link above. Paraphrased, the bulk of the "mainstream remarks include, "It's only in mice, and they had to used viral vectors." Well, if you will look at all the much-hyped embryonic "break-throughs," you will see that they are "only in mice" and many of them "used viral vectors."


Caplan, who notes the coincidental timing with legislation in Washington and who chronically sees bioethics through a political lens, couldn't pass up the chance for a rant on "embryos are not people." When I was an embryo, it was close enough for me - and my Mama. I actually agree with Art Caplan's comment that ". . . ditching embryos and jumping to fund alternatives is not the right response to this fascinating news about mouse cells." The reason we won't fund embryonic stem cell research requiring the distruction of human embryos is not because we have an alternative source. It's because we won't fund research that depends on the destruction of embryonic humans.

The abstracts for two of the articles are published on the Nature advance publication online page. (I don't yet have access to the third, in Cell's Stem Cell journal.

Nature advance online publication 6 June 2007 | doi:10.1038/nature05934; Received 6 February 2007; Accepted 22 May 2007; Published online 6 June 2007

Generation of germline-competent induced pluripotent stem cells
Keisuke Okita1, Tomoko Ichisaka1,2 & Shinya Yamanaka1,2
1. Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
2. CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan
Correspondence to: Shinya Yamanaka1,2 Correspondence and requests for materials should be addressed to S.Y. (Email: yamanaka@frontier.kyoto-u.ac.jp).

We have previously shown that pluripotent stem cells can be induced from mouse fibroblasts by retroviral introduction of Oct3/4 (also called Pou5f1), Sox2, c-Myc and Klf4, and subsequent selection for Fbx15 (also called Fbxo15) expression. These induced pluripotent stem (iPS) cells (hereafter called Fbx15 iPS cells) are similar to embryonic stem (ES) cells in morphology, proliferation and teratoma formation; however, they are different with regards to gene expression and DNA methylation patterns, and fail to produce adult chimaeras. Here we show that selection for Nanog expression results in germline-competent iPS cells with increased ES-cell-like gene expression and DNA methylation patterns compared with Fbx15 iPS cells. The four transgenes (Oct3/4, Sox2, c-myc and Klf4) were strongly silenced in Nanog iPS cells. We obtained adult chimaeras from seven Nanog iPS cell clones, with one clone being transmitted through the germ line to the next generation. Approximately 20% of the offspring developed tumours attributable to reactivation of the c-myc transgene. Thus, iPS cells competent for germline chimaeras can be obtained from fibroblasts, but retroviral introduction of c-Myc should be avoided for clinical application.
Although ES cells are promising donor sources in cell transplantation therapies1, they face immune rejection after transplantation and there are ethical issues regarding the usage of human embryos. These concerns may be overcome if pluripotent stem cells can be directly derived from patients' somatic cells2. We have previously shown that iPS cells can be generated from mouse fibroblasts by retrovirus-mediated introduction of four transcription factors (Oct3/4 (refs 3, 4), Sox2 (ref. 5), c-Myc (ref. 6) and Klf4 (ref. 7)) and by selection for Fbx15 expression8. Fbx15 iPS cells, however, have different gene expression and DNA methylation patterns compared with ES cells and do not contribute to adult chimaeras. We proposed that the incomplete reprogramming might be due to the selection for Fbx15 expression, and that by using better selection markers, we might be able to generate more ES-cell-like iPS cells. We decided to use Nanog as a candidate of such markers.
Although both Fbx15 and Nanog are targets of Oct3/4 and Sox2 (refs 9–11), Nanog is more tightly associated with pluripotency. In contrast to Fbx15-null mice and ES cells that barely show abnormal phenotypes9, disruption of Nanog in mice results in loss of the pluripotent epiblast12. Nanog-null ES cells can be established, but they tend to differentiate spontaneously12. Forced expression of Nanog renders ES cells independent of leukaemia inhibitory factor (LIF) for self-renewal12, 13 and confers increased reprogramming efficiency after fusion with somatic cells14. These results prompted us to propose that if we use Nanog as a selection marker, we might be able to obtain iPS cells displaying a greater similarity to ES cells.

and

Article Nature advance online publication 6 June 2007 | doi:10.1038/nature05944; Received 27 February 2007; Accepted 22 May 2007; Published online 6 June 2007

In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state

Marius Wernig1,6, Alexander Meissner1,6, Ruth Foreman1,2,6, Tobias Brambrink1,6, Manching Ku3,6, Konrad Hochedlinger1,7, Bradley E. Bernstein3,4,5 & Rudolf Jaenisch1,2
1. Whitehead Institute for Biomedical Research and,
2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
3. Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
4. Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
5. Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
6. These authors contributed equally to this work.
7. Present address: Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Harvard Medical School and Harvard Stem Cell Institute, Boston, Massachusetts 02414, USA.
Correspondence to: Rudolf Jaenisch1,2 Correspondence and requests for materials should be addressed to R.J. (Email: jaenisch@wi.mit.edu).

Nuclear transplantation can reprogramme a somatic genome back into an embryonic epigenetic state, and the reprogrammed nucleus can create a cloned animal or produce pluripotent embryonic stem cells. One potential use of the nuclear cloning approach is the derivation of 'customized' embryonic stem (ES) cells for patient-specific cell treatment, but technical and ethical considerations impede the therapeutic application of this technology. Reprogramming of fibroblasts to a pluripotent state can be induced in vitro through ectopic expression of the four transcription factors Oct4 (also called Oct3/4 or Pou5f1), Sox2, c-Myc and Klf4. Here we show that DNA methylation, gene expression and chromatin state of such induced reprogrammed stem cells are similar to those of ES cells. Notably, the cells—derived from mouse fibroblasts—can form viable chimaeras, can contribute to the germ line and can generate live late-term embryos when injected into tetraploid blastocysts. Our results show that the biological potency and epigenetic state of in-vitro-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells.

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.

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)