In the one-month period that transpired between April and May of this year, the National Institutes of Health received no less than 49,015 comments in response to the first draft of its new stem cell guidelines. The comments were submitted not only from people throughout the U.S. but also from people around the world who represent a broad spectrum of interests from the scientific and religious communities as well as from the public at large. NIH solicited and invited such comments, apparently thinking that matters which require a certain level of scientific expertise to understand can be decided democratically among the general public on the basis of majority vote. NIH did not disclose exactly how many of these nearly 50,000 comments were actually read, however.

As reported in Newsweek, "There has been something of a collective mood swing among stem cell scientists this year. Researchers were ebullient when President Obama lifted Bush-era restrictions on federal funding for embryonic stem cell research in March. But many were hugely disappointed when the NIH’s draft guidelines came out a month later." As has already been reported in related news articles on this website, one of the most hotly debated points in the new guidelines involves legalities of informed consent. As summarized in Newsweek, "Many of the (stem cell) lines developed from human embryos over the last decade would not meet these stringent new standards, and research using those cells would therefore be ineligible for government money." Among other organizations, the International Society for Stem Cell Research (ISSCR) stated in a letter to NIH that, "It is critical that a mechanism be developed to ensure that the past ten years of scientific progress with these lines not be lost to federally-funded research." (Please see the related news article on this website, entitled, "Embryonic Stem Cell Advocates Protest NIH Guidelines", dated May 25, 2009).

Another point of debate involves the procedure known as somatic cell nuclear transfer (SCNT), which can be used both for reproductive cloning as well as for so-called therapeutic cloning, neither of which are allowed under the new NIH guidelines although there are many scientists who wish to be able to use SCNT strictly for research purposes, despite the inherent risks.

Among the many religious groups who oppose embryonic stem cell research altogether and who advocate adult stem cell therapies instead, the United States Conference of Catholic Bishops also submitted a letter to NIH in which they stated their side of the argument. Unaffiliated with any religious group, however, are the many legitimate scientists and physicians who are already achieving great success with adult stem cells and who are eager to cite the many advantages of adult stem cells over embryonic stem cells, not for ethical or political reasons but purely for very concrete, scientific and medical reasons.

There remains one fundamental problem, however, which is rarely mentioned and which is therefore conspicuous by its absence in most debates over national stem cell policy in the United States. That problem has to do with the fact that the U.S. Food and Drug Administration (FDA) has insisted that the endogenous, autologous, naturally occurring adult stem cells, which are found in every human being’s body, should be classified as "drugs" and therefore must be regulated by the FDA and cannot be administered in any therapeutic manner, not even to the same person from whom the cells are derived, without first being subject to the same lengthy, lethargic, outdated approval process as a pharmaceutically manufactured drug, which is a process that typically takes a decade or longer and cost millions of dollars. This is the main reason why adult stem cell therapy is not available in the U.S. except to people who are accepted into a limited number of government-approved clinical trials, and this is precisely what is forcing legitimate adult stem cell physicians to relocate overseas, outside of the U.S., where even the most reputable and scientifically sound clinics must compete against the most disreputable and unscientific, and where it is not always easy for the patient-consumer to tell the two apart. A group of physicians, patients and other concerned citizens have formed a grass-roots advocacy movement in the U.S. in response to this grossly flawed stance by the FDA, and more info is available at www.safestemcells.org as well as at www.stemcelldocs.org. If it weren’t for the fact that each person’s own tissue and cells, which are found in each person’s own body, have been erroneously categorized as "drugs" by the FDA, subject to regulation and laws created by the FDA, then the numerous adult stem cell clinical therapies that have already been in use for years outside of the U.S. would also be available within the U.S., thereby rendering the debate over the hypothetical future clinical potential of embryonic stem cells irrelevant. (Please see the related news article on this website, entitled, "Two U.S. Adult Stem Cell Companies Form Collaboration in Asia", dated May 11, 2009).

Meanwhile, however, the debate rages on, with no realistic end in sight. Regardless of the details of the national stem cell policy which NIH is expected to unveil in its final form next month, however, there seems to be one point on which all parties can agree, which Newsweek summarized perfectly by stating, "Fireworks are expected one way or the other. Stay tuned."

All three people have improved after receiving a new type of adult stem cell therapy for the treatment of blindness caused by corneal disease.

In an article entitled, "A Contact Lens-Based Technique for Expansion and Transplantation of Autologous Epithelial Progenitors for Ocular Surface Reconstruction", scientists in Australia describe a novel method by which sight has been restored to 3 people who were suffering from limbal stem cell deficiency (LSCD). A painful condition that can result in blindness, LSCD is caused by a depleted pool of endogenous adult stem cells which ordinarily exist to replenish the epithelium of the cornea on a continuous basis throughout life. Without such naturally occurring, endogenous adult stem cells, blindness inevitably results from the deterioration of the cornea. Led by Dr. Nick Di Girolamo, the team of doctors describe a novel technique by which autologous (in which the donor and recipient are the same person) adult stem cells were utilized to restore the eyesight in 3 people with advanced LSCD. One of the most innovative aspects of this procedure was not so much the use of the autologous adult stem cells, per se, but the use of an FDA-approved type of contact lens as the substrate for the stem cells.

Autologous progenitor cells harvested from limbal and conjunctival biopsies were expanded on contact lenses which were then surgically transferred to each patient’s corneal surface. The stem cells began attaching to the corneas immediately, and the natural lens of each eye was able to be surgically removed by 2 weeks after transplantation. During a follow-up period which lasted 8 to 13 months, the doctors found that "a stable transparent corneal epithelium was restored in each patient." Additionally, "There was no recurrence of conjunctivalization or corneal vascularization, and a significant improvement in symptom score occurred in all patients. Best-corrected visual acuity was increased in all eyes after the procedure." Two of the 3 patients were legally blind in one eye prior to the procedure, but following the therapy they can now read large letters on an eye chart. The third patient is able to read the top rows of the eye chart and has also passed a vision test for a driver’s license. All three patients continue to see with the new lenses.

According to ophthalmologist Dr. Peter McCluskey of Sydney University who is also director of the Save Sight Institute, "I think it’s really exciting, innovative and novel." As Dr. Di Girolamo adds, "We’re quietly excited. We don’t know yet if it will remain stable, but if it does it’s a wonderful technique. It’s simple and easy for the patient and you don’t need fancy equipment, just an ophthalmic surgeon and a lab for cell culture."

As the doctors concluded in their paper, "Ex vivo expansion of ocular surface epithelium in the presence of autologous serum and transplantation with the aid of a soft CL (contact lens) is a promising new technique capable of achieving ocular surface rehabilitation."

In acute respiratory distress syndrome, inflammation and fibrosis result in loss of lung tissue which, according to a recent study, may be treated by mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are known to produce a number of growth factors and have been shown to inhibit fibrosis in liver failure as demonstrated by Parekkaden et al. in 2007, and to differentiate into pulmonary cells as reported by Sueblinvong et al. in 2007. Additionally, bone marrow mononuclear cells, which contain both hematopoietic stem cells and MSCs, have been used to treat pulmonary hypertension in an animal model. Now, scientists have tested the therapeutic capacity of MSCs derived from Wharton’s Jelly in an animal model of lung fibrosis.

Led by Dr. Yuben Moodley, scientists in Australia have reported the results of their study in a paper entitled "Human Umbilical Cord Mesenchymal Stem Cells Reduce Fibrosis of Bleomycin-Induced Lung Injury". The scientists obtained Wharton’s jelly from human umbilical cords derived from full-term, live, healthy births, from which the mesenchymal stem cells (MSCs) were then separated and administered to a mouse model of bleomycin-induced lung injury. Lung tissue was evaluated at one, two and four weeks post-bleomycin, from which the researchers observed that the MSCs were found to have migrated only to those areas of inflammation and fibrosis but not to healthy tissue.

As the scientists describe in their paper, the administration of the MSCs reduced inflammation and inhibited the expression of various signaling chemicals which contribute to inflammation, including a number of proinflammatory cytokines. The scientists therefore concluded that MSCs "have antifibrotic properties and may augment lung repair if used to treat acute respiratory distress syndrome."

A glycopeptide antibiotic that is produced by the bacterium Streptomyces verticillus, bleomycin is commonly used in cancer chemotherapy but is well known for a number of serious side effects which include pulmonary fibrosis and other types of impaired lung function, due to the role of bleomycin in producing a number of proinflammatory cytokines and inducing oxygen toxicity.

Wharton’s jelly, named after the 17th century anatomist Thomas Wharton, is the gelatinous, mucosal substance found within the umbilical cord and is a rich source of hyaluronic acid, chondroitin sulfate and adult stem cells, among other substances.

In a letter to the editor of The Washington Post, Cynthia Cohen, Ph.D., J.D., Senior Research Fellow at the Kennedy Institute of Ethics at Georgetwon University in Washington, D.C., points out a few pros and cons of the recently proposed NIH guidelines.

Among other things, Dr. Cohen addresses "the grandfathering brouhaha", as she calls it, or in other words, "the storm raised by stem-cell scientists about the failure of the National Institutes of Health draft guidelines to grandfather in stem-cell lines already in use". Under the initial draft of the proposed NIH guidelines, certain conditions would render ineligible for federal funding many of embryonic stem cell lines that already exist, which has caused a loud uproar among embryonic stem cell scientists. (Please see the related news article on this website, entitled, "Embryonic Stem Cell Advocates Protest NIH Guidelines", dated May 25, 2009).

According to Dr. Cohen, she does not see this as an irreconcilable problem, but instead points out that, "The guidelines admirably add certain protections for those who make the difficult decision to donate, for stem-cell research, embyros remaining after in vitro fertilization treatment. Such protections did not appear in the Bush-era guidelines. While the protections complicate the informed-consent process, the grandfathering issue they raise can be remedied by adopting sections of the National Academy of Sciences guidelines addressing it."

Of greater concern, Dr. Cohen explains, "is that the NIH draft guidelines do not provide for oversight of stem-cell research at the institutional or national levels. In contrast, such oversight is called for by the National Academies, by the 2000 NIH stem-cell task force and by the 1999 report of the National Bioethics Advisory Commission." Having served as a member of Canada’s Stem Cell Oversight Committee, Dr. Cohen is speaking from personal experience when she points out that, "Oversight of stem-cell research has been generally appreciated by scientists in Canada, because it has enabled them to avoid ethical and policy pitfalls that could delay their research." Indeed, such a concept is hardlly new in the U.S., as Dr. Cohen cites the formal requirement of such oversight even in 1999 by the National Bioethics Advisory Commission which existed under the Clinton administration.

Although Dr. Cohen concedes that the NIH draft guidelines make "a good first stab" at addressing a variety of complex issues, she also points out that "these and other sorts of ethical and policy concerns will need to be addressed in the final NIH guidelines".

Dr. Cohen has written extensively on issues of medical bioethics over the years, including "The Interests of Egg Donors: Who is Deceiving Whom?" which was published in the Fall 2001 issue of The American Journal of Bioethics, "Creating Human-Nonhuman Chimeras: Of Mice and Men" which was published in the Summer 2003 issue of The American Journal of Bioethics, and her latest book, "Renewing the Stuff of Life – Stem Cells, Ethics, and Public Policy", which was published in 2007 by Oxford University Press.

Fate Therapuetics, located outside of San Diego in La Jolla, California, announced today that the first patient has been treated in a clinical trial for hematopoietic stem cell support. The Phase 1b study is testing FT1050, a proprietary small molecule stem cell modulator (SCM) which is being administered in a dual cord blood transplant for hematologic malignancy. Among other properties, FT1050 has been designed to activate specific pathways that determine the "fate" (the direction of differentiation and ultimate cell type, i.e.) of a stem cell, the purpose of which in this particular context is to increase hematopoietic stem cell number and function in the treatment of hematologic malignancies such as leukemia and lymphoma in adult patients who have undergone nonmyeloablative conditioning. The study is being conducted at the Dana-Farber Cancer Institute in Boston, where FT1050 is being administered during the standard course of dual umbilical cord blood transplants.

As Dr. Paul Grayson, president and CEO of Fate Therapeutics, explains, "The mission of Fate Therapeutics is to develop small molecules and biologics that modulate adult stem cells within the body for regenerative medicine. As our first SCM clinical candidate, FT1050 represents the initial step in our approach – using a small molecule to treat cells ex vivo but creating an in vivo regenerative effect. With FT1050, we are trying to affect stem cell biology in the body, improving the reconstitution of a patient’s blood and immune system."

According to Dr. Corey Cutler, assistant professor of medicine at Harvard Medical School and the director of the clinical study at Dana-Farber, "For patients who need hematopoietic stem cell support, time is of the essence. However, many patients do not have a suitably matched donor, either from a sibling or from an unrelated volunteer in the worldwide registries. Because umbilical cord blood units are readily available from cord blood banks, and the matching criteria for cord blood are less stringent than with adult donors, the ability to increase cord blood use by enhancing its efficiency has the potential to help thousands of patients waiting for a match." Twelve patients are expected to be enrolled in the trial for FT1050, which has been demonstrated to mediate not only stem cell differentiation pathways but also the ability of stem cells to "home in" on, and target, the bone marrow, thereby repopulating the patient’s own blood and immune system.

Patients with hematologic malignancies such as leukeia and lymphoma who do not respond to conventional therapies are often treated with intensive radiation, chemotherapy and additional forms of high-dose immunotherapy which often destroy the patient’s healthy blood and immunological systems in addition to the cancer cells. Bone marrow restoration through hematopoietic reconstitution is therefore necessary for the survival of such patients. In this as well as other types of clinical settings, adult stem cells obtained from umbilical cord blood have a number of therapeutic and logistical advantages over bone marrow or peripheral blood transplants, including but not limited to ease of matching HLA (human leukocyte antigen) markers as well as "faster availability, lower incidence and severity of acute graft-versus-host disease, lower risk of transmitting infections by latent viruses, lack of donor attrition and no risk to the donor", among other advantages, as described in the official press release of Fate Therapeutics. Additionally, as described on the company’s website, when compared to bone marrow and peripheral blood transplants, "cord blood is less immunogenic, which means it is less likely to be rejected by the patient’s immune system", and "cord blood is more readily available, which reduces medical costs and procedures necessary with obtaining stem cells from bone marrow or a patient’s or donor’s blood." Additionally, "cord blood has been used in hematopoietic stem cell support since 1988", and its safety and efficacy are well documented in the medical literature.

As also stated in the press release, "FT1050 was discovered by Leonard Zon, M.D., director of the Stem Cell Program at Children’s Hospital Boston and a scientific founder of Fate Therapeutics and is part of an exclusive license granted to Fate by Children’s Hospital Boston and Massachusetts General Hospital."

(Please see the related news article on this website, entitled, "Children’s Hospital of Boston and Fate Therapeutics Sign IP Deal", dated May 20, 2009).

In a strong sign of discontent, contrasting sharply with the enthusiasm that accompanied President Obama’s putative reversal of embryonic stem cell federal funding restrictions earlier this year, embryonic stem cell scientists have now concluded that Obama’s new policy would have the opposite effect and would instead impose new restrictions.

At the crux of the argument is the new set of guidelines proposed by the National Institutes of Health which would render ineligible for federal funding most of the current embryonic stem cell research that is already in progress and which is already receiving either federal or private funding. Contrary to popular misconception, the Bush administration did not forbid embryonic stem cell research altogether, and embryonic stem cell research has been alive and well throughout the U.S. for years, even predating the Bush administration. Now, however, under the Obama administration, the anticipated increase in the number of embryonic stem cell lines that would be eligible for federal funding is now instead jeopardized by new NIH guidelines which would actually decrease the number of eligible embryonic stem cell lines, thereby having the exact opposite effect of that which embryonic stem cell scientists had expected. In fact, under the new NIH guidelines, most of the embryonic stem cell research which is currently already in progress would suddenly be rendered ineligible and would have to be shut down.

According to Amy Comstock Rick, chief executive of the Coalition for the Advancement of Medical Research, "We’re very concerned. If they don’t change this, very little current research would be eligible. It’s a huge issue." As Dr. Lawrence Goldstein, director of the stem cell program at the University of California at San Diego, adds, "It’s not that past practices were shoddy. But they don’t necessarily meet every letter of the new guidelines moving forward. We’d have to throw everything out and start all over again."

One particularly contentious point in the new NIH guidelines pertains to issues of informed consent. Couples who donate their embryos for research would now be required to sign a consent form acknowledging that they were fully informed of other options, such as the possibility of donating their embryos to other couples for the purpose of allowing the embryos to grow and be born as children. Currently, not all IVF (in vitro fertilization) clinics present such options to couples, and those clinics which do discuss such options with their clients do not always have the information specified in writing.

As Dr. George Daley of the Harvard Stem Cell Institute explains, "They take 2009 standards and attempt to apply them retroactively, which isn’t really a standard that would allow most of the preexisting lines to be acceptable for NIH funding. This is essentially moving the goal post."

According to Dr. Patrick Taylor, deputy counsel of Children’s Hospital in Boston, whose critique of the proposed NIH guidelines appeared last month in the journal Cell Stem Cell, "If applied retroactively, the proposed guidelines would render ineligible most stem cell lines."

Raynard Kington, acting director of the NIH, declined further comment other than to state, "We know issues like this, among many issues, have been raised, and we will take them into consideration."

NIH published their first proposed draft of the new guidelines on April 17. The final version is expected to be released by July 7.

(Please see the following related news articles on this website: "NIH Issues Guidelines Restricting Embryonic Stem Cell Research", dated April 17, 2009; "Members of The President’s Council on Bioethics Object to Obama’s Stem Cell Policy", dated March 26, 2009; "A High-Profile Proponent of Embryonic Stem Cell Research Sharply Criticizes Obama’s Policy", dated March 13, 2009; "Obama Signs Law Restricting Federal Funding of Embryonic Stem Cell Research", dated March 11, 2009; "Obama Rescinds Bush-Era Executive Order Pushing for More Ethical Stem Cell Research", dated March 10, 2009; "Obama Decrees Changes in Embryonic Stem Cell Research, Though Not What One Might Expect", dated March 9, 2009; and "Former Director of N.I.H. Explains Why Embryonic Stem Cells are Obsolete", dated March 4, 2009).

The biotech company Fate Therapeutics has announced an IP agreement that involves technology licensed primarily from Children’s Hospital of Boston as well as technology developed at Massachusetts General Hospital, also of Boston. Based in San Diego and known for what it calls its "adult stem cell biology engine", Fate Therapeutics has entered into a number of IP agreements in recent months, and this is the seventh in a series of licensing deals between Fate and various research or academic institutions. Although the precise details were not disclosed, the latest agreement involves technology for supporting hematopoietic stem cell development. Dr. Len Zon, director of the stem cell program at Children’s Hospital and a co-founder of Fate Therapeutics, develped the technology.

Fate Therapeutics had previously licensed technology from Mass General which was developed by Dr. David Scadden, another co-founder of Fate Therapeutics who also co-founded and co-directs the Harvard Stem Cell Institute and who is also currently director of the Center for Regenerative Medicine at Mass General Hospital. According to Seema Basu, senior business strategy and licensing manager with the Office of Corporate Sponsored Research and Licensing at Mass General Hospital, "Depending on how the clinical development pans out, they could have different applications. There are many steps to that system’s biology, and they all complement each other. A lot will pan out once Fate does more clinical development. We’re excited that a therapeutic company is trying to take this technology into clinical development."

Founded in 2007, Fate Therapeutics was originally organized from research that had been conducted at Mass General, Stanford University, Harvard University, the University of Washington and The Scripps Research Institute. Although the company’s primary focus is adult stem cells, it is also developing iPS (induced pluripotent stem) cell technology. While iPS cells are not, in the technically strict sense of the term, "adult stem cells" – because iPS cells are derived from adult somatic cells (which are merely ordinary, mature, differentiated cells and are not stem cells) – the more important point is that iPS cells, like adult stem cells, are also not derived from embryonic stem cells even though iPS cells exhibit the same pluripotency as embryonic stem cells.

According to Fate president and CEO Paul Grayson, "Over the past two years, Fate Therapeutics has amassed extensive intellectual property assets as a foundation for our adult stem cell biology engine. The agreement we signed today with Children’s Hospital and the technologies associated with it continue to expand our engine and accelerate the company’s core mission to develop small molecules and biologics that modulate adult stem cells for regenerative medicine."

As the name implies, the company uses small molecules and biologics to guide and direct the "fate" – i.e., the ultimate direction and differentiation type – of cell development. Such techniques apply not only to adult stem cells but also to mature adult somatic (non-stem cell) cells which can be modulated and reprogrammed back to a more primitive state in which the cells exhibit a pluripotency similar to that of embryonic stem cells. As stated on the company’s website, "Fate Therapeutics is focusing on adult stem cells and induced pluripotent stem (iPS) cells. Adult stem cells naturally exist in tissues or organs and are responsible for maintaining and repairing the tissue in which they are found. iPS cells are stem cells created from fully mature differentiated cells, like a skin cell, and promise to be of great use for drug discovery and development and personalized cell replacement therapies."

As also stated on their website, "Fate’s scientific founders have identified and characterized key stem cell pathways, such as Wnt, Hedgehog and Notch, which are known to regulate cell fate and play key roles in tissue repair and regeneration and iPS cell creation." By harnessing the molecular mechanisms of such cellular pathways, Fate is developing therapeutic programs that have clinical applications not only across the broad spectrum of regenerative medicine, such as in the treatment of traumatic injury and degenerative diseases, but also in other fields such as metastatic cancer and hematological diseases. In a company statement, Fate therapeutics announced that, "The discovery of a number of conserved mechanisms from developmental biology and tissue repair has led to the identification of small molecules and biologics that can direct stem cell proliferation and function. Fate is developing these small molecule and biologic stem cell modulators to modulate the activity of adult stem cells to stimulate healing or block cancer growth."

Shortly after Fate’s founding in 2007, Dr. Sheng Ding, associate professor of chemistry and cell biology at The Scripps Research Institute who is also one of Fate’s co-founders, explained that Fate Therapeutics "is really about a collection of small molecules and protein therapeutics for modulating stem cell fate in vivo. That’s a totally different approach", he says, from other stem cell companies that "are using cells, and are primarily focused on cell-based therapies."

In April of this year, Fate Therapeutics and the Boston-based company Stemgent announced a strategic alliance, known as Catalyst, which is "a collaborative one-of-a-kind program to provide pharmaceutical and biotechnology companies with the most advanced induced pluripotent stem (iPS) cell technology platform for drug discovery and development", as described on the website of Fate Therapeutics. The novel technology utilizes protein-based reprogramming methods developed by Dr. Sheng Ding which constitute "a technique that effectively eliminates any risk of genetic modification" and which is free of oncogenic and viral reprogramming factors.

(Please see the related news article on this website, entitled, "First Patient Treated in Clinical Trial for Hematopoietic Stem Cells", dated May 27, 2009).