According to Dr. Steve Duncan, professor of human and molecular genetics at the Medical College of Wisconsin, the failure of the new NIH Guidelines to "grandfather" in the already existing hESC lines has had a "tremendously detrimental effect on our research."

As Dr. Duncan explains, "The problem is they haven’t added the presidential lines as a group of lines that we can now use. So we can’t do any human embryonic stem cell (hESC) research with new federal funds at this point. We’re hoping within the next two months that it will be relaxed, but that’s a long time in research and it’s reallly upsetting, the way it’s been handled."

Once again, as previously reported a number of times on this website, at the heart of the debate are the "voluntary and informed consent" rules which are contained within the new NIH Guidelines. Many, if not all, of the hESC lines that already exist were created before such rules of consent were authored, and therefore do not meet "the core ethical principles and procedures" that are defined in the new NIH Guidelines. Even though NIH says that such hESCs are subject to review by an advisory committee and might therefore be "grandfathered" in, there is still widespread doubt among the ESC scientific community that many of those lines will be approved for the federal funding of research.

In fact, contrary to popular opinion, there is one major obstacle in the U.S. which is preventing stem cell therapies from being available in clinics at this very moment, and that obstacle has nothing to do with NIH nor with embryonic stem cells nor with any restrictions that the Bush administration supposedly imposed nor with any restrictions that the Obama administration supposedly lifted. Instead, that one, single, primary obstacle is the fact that the U.S. FDA (Food and Drug Administration) has decreed that autologus (in which the donor and recipient are the same person) adult stem cells are a "drug", and therefore must be regulated as such, and therefore cannot be used for therapeutic purposes in the U.S. without having first been subjected to the lengthy, lethargic, outdated, multi-year, multi-million dollar federal governmental approval process, in the same manner as which pharmaceutically manufactured drugs are regulated. Such a stance is without any scientific basis whatsoever, and a number of individuals and organizations are attempting to initiate a much-needed and long-overdue reform of the FDA on this issue. Until the FDA is completely overhauled, however, it seems as though U.S. academicians will continue to focus all of their time and attention on arguing over the federal funding of embryonic stem cell research while apparently remaining oblivious to the fact that doctors and patients are not willing to sit around and wait another decade for something to happen, but instead are traveling overseas where adult stem cell therapies are already available in clinics in just about every country in the world except the United States. (Please see the related news articles on this website, entitled, "Arizona Man Travels to Central America for Adult Stem Cell Therapy", dated July 16, 2009; "Bangor Family Heads to Central America for Adult Stem Cell Therapy", dated July 8, 2009; "Texas Woman Travels to Central America for Adult Stem Cell Treatment", dated June 25, 2009, and "Two U.S. Adult Stem Cell Companies Form Collaboration in Asia", dated May 11, 2009).

Despite all the exaggerated hype over embryonic stem cells, usually at the complete exclusion of adult stem cells, Dr. Duncan nevertheless predicts that future stem cell research will shift more toward adult rather than embryonic stem cells, and not just for the numerous sound scientific and medical reasons but also for ethical reasons as well. Despite his own interest in hESC research at the moment, he also pointed out that, "I think we have to take into account the ethical situation."

President Obama issued Executive Order 13505 on March 9, 2009, to establish policy and procedures under which NIH (National Institutes of Health) will fund research in the area of embryonic stem cells. Previously, embryonic stem cell research was legal in the US, as long as it was not funded by the NIH. However, NIH funded research in embryonic stem cells could be conducted as long as it involved existing embryonic stem cell lines, and not creation of new ones. As a response to the Executive Order, the NIH generated draft Guidelines that would allow funding for research using human embryonic stem cells that were derived from embryos created by in vitro fertilization (IVF) for reproductive purposes and were no longer needed for that purpose.

There were approximately 49,000 comments sent into the NIH in response to a publicly available draft of the new guidelines to embryonic stem cell research (see for yourself at http://grants.nih.gov/stem_cells/web_listing.htm). According to the article by Nancy Frazier O’Brien of the Catholic News Service, although many of them were repetitive, some made clear the point that destruction of human embryos should not be permitted. For example, one comment was:

"As a mother of a child with juvenile diabetes, I certainly hope we find a cure for this terrible disease in her lifetime," wrote one woman. "However, I am not willing to sacrifice the life of ONE CHILD, let alone thousands or even more in the name of research.

Currently much research is being performed on embryonic stem cells in order to develop treatments and eventually cures for diseases that currently are incurable. At least this dream is what inspires many to support embryonic stem cell research. Unfortunately, much of the political debate, at least in our opinion, seems to be just that: politics.

The whole purpose of medical research is the development of new treatment that help people. This is not to say that there is something wrong with doing research for the sake of doing research. After all, many of the greatest advancements of humanity came about by accident when people were not looking for them. So there is a point to doing basic research for the sake of basic research. However, the media and the political debates around embryonic stem cells are giving the impression that if people do not support embryonic stem cells, they are not supporting cures for their children with diabetes, or their parents with Alzheimer’s or Michael J Fox’s Parkinson’s. In fact, nothing could be farther from the truth.

The field of embryonic stem cell research is based on the finding that if one takes a fertilized egg and extracts specific cells after the fertilized egg has developed to a certain point, these cells, can give rise to every cell in the body. Interestingly, these "master cells" can be grown in high quantities under special conditions so that they can be used for experiments. For example, these embryonic stem cells can be treated with certain chemicals and make muscle cells in the test tube. These cells can be treated with other chemicals and make brain cells in the test tube. These cells can make almost any cell known to mankind when manipulated in the test tube. This sounds very exciting. This is why many people are very excited about embryonic stem cell research.

Now the problem is a little more complex.

When these "master cells", these embryonic stem cells, are placed into a mouse that has been induced to have a heart attack, what happens to these cells? Unfortunately, what happens, is that the mouse developed more inflammation, or some mice develop a cancer called a teratoma. So the beautiful and exciting work in the test tube, has so far largely failed to produce therapeutic results in animals. We know that cancer has been cured in animals for decades now, yet some many humans still die of cancer. If we can not induce cures in animals with embryonic stem cells, then how likely are we to induce cures in humans in the near future?

Exactly. The point that embryonic stem cell advocates make, the ones that have some familiarity with medical science (which most don’t), is that just because embryonic stem cells are not useful today does not been that they will not be useful tomorrow. That research dollars need to be spent on embryonic stem cells so that one day they may be useful.

We can not argue with the point of supporting basic research. However, our position is that basic research should be seen as basic research and should not be transformed into a "religion".

There are several points that need to be made that are not made out of belief, or politics, or even religion, but are based on scientific facts:

Firstly, embryonic stem cells have made medical progress already. The creation of genetically engineered mice (knockouts and transgenics) was soley dependent on mouse embryonic stem cells. Practically everything we know scientifically about the function of molecules in living things has been derived from these animals. Accordingly, the blanket statement that embryonic stem cells have produced no benefits is incorrect.

Secondly, adult stem cells have been used already in patients with various degrees of success. For example, in patients with heart failure, analysis of over 1000 patients indicated overall improvement of heart function. Now where would money and funds be better spend? Taking something that seems to work and making it applicable to everyone, or chasing a distant dream?

Thirdly, embryonic stem cell research, from a scientific perspective, is rapidly becoming obsolete. The moral and ethical issues surrounding embryonic stem cells arise from the need to destroy the embryo to extract the embryonic stem cells. The new technology called inducible pluripotent stem cells (iPS) allows for the generation of brand new embryonic-like stem cells from skin, bone marrow, brain, and pretty much any other tissue. What many supporters of embryonic stem cells do not know is that iPS cells are more attractive to scientists because: a) they can be easily generated; b) they offer potential to make "brand new", "clean" cells, without having to rely on embryonic stem cells that are years old and have undefined characteristics; and c) iPS cells allow the possibility to make stem cells from the same patient.

On July 6th, 2009 Dr. Raynard S. Kington, acting NIH director, made final the guidelines and approved funding for research involving the creation of new ES cells. The question now becomes how much of the funding should support ES research and how much support with the other stem cell technologies be given, the technologies that actually seem to be inducing benefit in people today?

Today at the ISSCR Meeting in Barcelona, the merger of two stem cell companies, IZumi Bio and Pierian Inc was announced, with the new company being named IPierian. According to the new company’s website iPierian is

"…a pioneering biopharmaceutical company that is taking the cutting-edge technologies of cellular reprogramming and directed differentiation to an entirely new level to harness the power of induced pluripotent stem cells to advance the understanding of human diseases and accelerate the discovery of more effective therapeutics for patients"

The two precursor companies, iZumi and Pierian, both had synergistic skills in the area of inducible pluripotent stem cells (iPS), a type of "artificial stem cell" that is created from skin or other tissues. The use of iPS cells for therapeutics development is more attractive to scientists than embryonic stem cells for several reasons. Firstly, iPS cells can be generated to be patient-specific, thus overcoming problems with need for taking of immune suppressants. Currently embryonic stem cells can not be used in patients for several reasons, and the few times that their use is contemplated, the patient is sentenced to taking life-long immune suppression so that they do not undergo rejection. Secondly, iPS cells can be generated under highly defined conditions. Embryonic stem cells that are currently used have been developed years ago and face various problems such as the fact that many of them have previously been grown on mouse cells or using animal products. In contrast, iPS cells can be generated with relatively little effort.

iZumi was supported by the venture capital groups Kleiner Perkins Caufield & Byers and LExington, Mass.-based Highland Capital Partners with a $20 million investment, whereas Pierian was founded by MPM Capital managing directors Ashley Dombkowski and Robert Millman as well as Harvard University scientists. The new company, which will be led by John Walker as CEO and Corey Goodman, as Chairman, raised an additional $10 million from Boston-based MPM Capital and $1.5 million from FinTech Capital Partners.

Initial goals of the company will be use of the iPS cells to address disease affecting the central nervous system that have no effective treatment such as spinal muscular atrophy, Parkinson’s Disease, and ALS. In the long-run the company plans to investigate conditions such as heart failure, liver failure, and diabetes. As part of the new company’s strategy, it will seek synergistic collaborations with established market players.

Despite the aggressive goals the company has set for itself, there are several drawbacks that one must consider. Firstly, pluripotent stem cells, regardless of whether they are iPS or embryonic stem cells, all cause cancer when administered into animals. iPS may be especially dangerous since oncogenes (genes that cause cancer) are needed for the creation of these cells. In order for iPS to be used safely, it will be necessary to make sure that the cells being made for injection are completely the cells that one wants, and no contamination with the original iPS cells. In other words, if one is treating Parkinson’s Disease, one can not simply inject iPS cells into the area of the brain that is damaged, since this conceptually will form a tumor. In contrast, one would have to "teach" the iPS cells to become the specific cell that is damaged in Parkinson’s Disease, called the "dopaminergic neuron", one will have to concentrate these cells outside of the body, and then inject them directly where they are needed. Once the cells are injected, they will have to form connections with the existing cells and subsequently integrate and take over their function. This is in contrast to the present-day clinically available adult stem cell therapies, where in many cases adult stem cells are injected either intraviously or intrathecally, and the natural signals of the body instruct them to differentiate into the needed tissue. Although differentiation efficacy of adult stem cells may be lower on a per cell basis, of the thousands of people that have been treated with adult stem cells no reports of tumor formation exist.

iPierian’s scientific leadership comes from the respected embryonic stem cell experts Dr. George Daley, Douglas Melton and Lee Rubin who are faculty at Harvard. The scientific advisory board (SAB) of the company will be chaired by Dr. George Daley, and will include Amy Wagers, Kevin Eggan, Benoit Bruneau, and Matthias Hebrok.

When Ken Milles suffered a heart attack at the age of 39, he was not given a very encouraging prognosis from his doctor. As Ken describes, "When he told me that there was permanent damage and that the duration of my life was reduced, that freaked me out."

A construction worker and father of two teenaged sons, Ken is now the first patient to volunteer in a clinical trial at the Cedars-Sinai Heart Institute in Los Angeles. One of 24 patients in the study, Ken is the first person to be treated with his own heart-derived adult stem cells.

Adult stem cells are believed to reside in all tissue types throughout the body, with each type of adult stem cell being highly specialized in producing the corresponding specific type of tissue. Some organs, such as the heart, are known to contain very small amounts of their own stem cells, but nevertheless a specialized cardiac stem cell is known to exist in the adult human heart, throughout life and into old age. The low number of naturally occurring, endogenous cardiac stem cells, however, is not usually enough to repair serious damage to heart tissue, such as that which results from myocardial infarction. But when these cardiac stem cells are isolated, cultured and expanded in the laboratory, they can be readministered to the patient in quantities that are large enough to repair even severe damage. This is exactly what Ken’s doctors are doing.

As Dr. Eduardo Marban, the leader of the study, describes, "We seek to actually reverse the injury that has been caused by the heart attack, by regrowing new heart muscle to at least partially replace the scar that’s formed. These cells that we’re putting in come from the heart itself, and are predestined to generate heart muscle and blood vessels."

Derived from a tiny sample of healthy heart tissue, the cardiac stem cells are expanded in the laboratory to 25 million stem cells, which then develop into the spherical, multicellular structures known as cardiospheres which have been found in previous clinical and preclinical trials to regenerate damaged cardiac tissue. In fact, Dr. Marban was involved in similar studies at the Johns Hopkins University School of Medicine in 2005, at which time he reported that, "The findings could potentially offer patients use of their own stem cells to repair heart tissue soon after a heart attack, or to regenerate weakened muscle resulting from heart failure, perhaps averting the need for heart transplants. By using a patient’s own adult stem cells rather than a donor’s, there would be no risk of triggering an immune response that could cause rejection."

The doctors inject the stem cells through an artery directly into the damaged tissue of the patient’s heart. Within 6 months, signs of tissue repair should become evident.

As Ken Milles has said, "If this works, it’s gonna help so many people. It’s gonna change everything."

The clinical trials will continue for the next 3 to 4 years.

The adult stem cell company Aastrom Biosciences has resumed patient enrollment in its Phase II clinical trial, entitled IMPACT-DCM, in which autologous adult stem cells are being used to treat dilated cardiomyopathy, an end-stage form of chronic, congestive heart failure. The study had been suspended on May 22 when a patient in the trial died. The U.S. Food and Drug Administration has now concluded that the death of the patient was unrelated to the clinical trial.

On May 22 it was announced that the clinical trial was suspended when a patient who was enrolled in the trial unexpectedly died after having been treated with autologous (in which the donor and recipient are the same person) adult stem cells and released from the hospital. The FDA then imposed a halt on the clinical trial, at which time Aastrom temporarily suspended further patient enrollment and treatment until the cause of death could be determined. Having completed its formal investigation, the FDA has now concluded that the cause of the patient’s death was unrelated to the clinical trial itself, but instead was merely caused by the advanced stage of the patient’s own dilated cardiomyopathy. Since the clinical trial was specifically designed to treat dilated cardiomyopathy, this disease was required as a preexisting condition for enrollment in the clinical trial, although some patients who were enrolled had more advanced and severe forms of this condition than others.

Fourteen people have been enrolled in the study thus far, which has a target enrollment of 40 patients. The dilated cardiomyopathy study is not Aastrom’s only clinical trial currently underway, however, as Aastrom is also conducting a Phase IIb clinical trial for the treatment of critical limb ischemia, an advanced form of peripheral artery disease, which is also being treated with autologous adult stem cells. According to the Aastrom’s website, "The Company’s proprietary Tissue Repair Cell (TRC) technology involves the use of a patient’s own cells to manufacture products to treat a range of chronic diseases and serious injuries. Aastrom’s TRC-based products contain increased numbers of stem and early progenitor cells, produced from a small amount of bone marrow collected from the patient." Aastrom describes itself as a "Regenerative medicine company developing personalized cell-based therapies to slow or reverse the course of chronic diseases." As stated on their website, "Aastrom’s TRC products have been used in over 325 patients, and are currently in clinical trials for cardiac, vascular and bone tissue regeneration applications, with plans to expand into the neural therapeutic area."

Headquartered in Ann Arbor, Michigan, Aastrom is focused exclusively on therapies that are developed from autologous adult stem cells, not embryonic stem cells.

Aastrom’s stock price climbed 21.8% following today’s news announcement by the FDA.