The Anthony Nolan Trust Cord Blood Bank, with facilities in London and Nottingham, is launching a new project that will accommodate the storage of adult stem cells derived from the blood of 50,000 umbilical cords. The project is one of the largest of its kind, and fundraising plans have targeted a goal of 27 million pounds through charitable donations for the projected growth of the organization.

According to the British Minister of Health, Alan Johnson, who opened the center, “For most transplants, the reality is that someone else has to die and donate their organs for another to live. But with bone marrow and cord blood, this is clearly not the case. Bone marrow can be easily and painlessly donated via a single operation. Cord blood offers further potential to change and save lives. Collected, processed and stored at birth, it becomes part of a global life-saving resource. The Anthony Nolan Trust is already acclaimed worldwide, and the impact of the events here today will be felt globally. The complex will help provide a lifeline for thousands complementing the 12 years experience of the NHS Cord Blood Bank, and reinforce the UK’s role as a research center of excellence.”

The institute is planning to match the 400,000 potential donors listed in the Bone Marrow Register of the same charity, which expanded into cord blood stem cells 5 years ago. Of the 50,000 umbilical cord donations that are designated for storage by 2012, 30,000 are planned for research, and the other 20,000 for transplantation. According to Dr. Steve McEwan, Chief Executive of the charity, “The beauty of this new program will not only be to save the lives of hundreds more patients but also to provide researchers the opportunity to develop innovative new treatments using cord blood.”

Prior to expanding into cord blood stem cell research, The Anthony Nolan Trust was focused on leukemia research and bone marrow transplantation. The eponym of the organization was Anthony Nolan, who lived from 1971 to 1979 and who died from a rare blood disorder of genetic origin known as Wiskott-Aldrich syndrome. While the headquarters of the Trust are located in north London, a new facility has just opened on the grounds of Nottingham Trent University, where the company Clean Modules Ltd. has just completed the Cord Blood Cleanroom Centre, where the cord blood stem cells will be processed and stored.

The embryonic stem cell company, Advanced Cell Technology (ACT), of Worcester, Massachusetts, has announced that it plans to vacate its Charleston facility and it also will not renew its lease on a California research center. The announcement comes as part of the company’s plan to eliminate $5 to $6 million from its annual operating budget, in the face of escalating debt.

According William Caldwell IV, CEO, “Near-term funding continues to be our major challenge. The company plans to spend its remaining cash on the most advanced clinical programs.” Other executives in the life sciences who were interviewed attribute ACT’s financial troubles to inflated and unsubstantiated claims regarding embryonic stem cells, which included early reports of cloned human embryos and the embryos of endangered species which later proved to be unverifiable.

In an S.E.C. filing in July of this year, ACT reported $1 million in assets and $17 million in liabilities. According to a company representative, ACT attributes its own financial problems to a heavy dependence on “emerging and sometimes unproven technologies” within an “ethically sensitive and controversial” broader context.

Last month, ACT received $250,000 in initial payment for a licensing agreement with Embryome Sciences, a subsidiary of BioTime, Inc, currently directed by Michael West who was formerly the CEO of ACT.

The recipients of the coveted Shaw Prize this year include Sir Ian Wilmut and Dr. Keith Campbell of the U.K., and Dr. Shinya Yamanaka of Japan, all of whom shared the million-dollar life sciences award. According to an official statement released by the organizers of the event, “Based on these discoveries, animal experiments by others have already shown that it was possible to cure mouse models of sickle cell anemia and Parkinson’s disease.”

Although Dr. James Thomson of the University of Wisconsin at Madison is widely recognized as the first to conduct iPS cell procedures on human skin cells, Dr. Yamanaka of Kyoto University preceded Dr. Thomson’s work by performing the first iPS procedure on mouse fibroblasts in 2006.

Sir Ian Wilmut has often been in the news lately, not so much for his cloning of Dolly the Sheep as for his statement that he is abandoning the field of cloning in order to shift his focus to adult stem cells, which he believes merit the greatest attention.

Established in 2002 by a Hong Kong film producer and philanthropist, the Shaw Prize is actually three separate prizes, which are awarded for outstanding achievement in the life sciences, the mathematical sciences, and astronomy. Each of the awards consists of one million dollars in cash.

The Chairman and CEO of NeoStem, Robin Smith, M.D., MBA, has been invited to present a talk on the growing phenomenon known as “medical tourism”, and its implications, at the upcoming World Stem Cell Summit to be held in Madison, Wisconsin from September 21st through the 23rd.

In 2007, approximately 750,000 Americans traveled abroad in search of medical care, and this number is projected to reach 6 million by 2010. Similarly, of all international travelers who leave their home country to find medical care elsewhere, approximately 40% of those people are non-Americans who travel to the United States for medical treatment, according to a McKinsey report that was issued in May of 2008. Medical companies and clinics that are strategically located within major destination cities within the U.S. are therefore likely to profit from this growing global trend toward “medical tourism” – especially in the field of stem cells.

According to Dr. Smith, “We have already begun to see international interest as evidenced by a collection performed at a NeoStem center in New York last week on an individual who lives in Dubai. NeoStem believes that individuals in increasing numbers will seek safe and effective stem cell therapies abroad that are not yet approved in the United States and many important clinical advances will be in hospitals and clinics outside the United States. We believe that we could gain value from this by including medical tourism in the company’s future business strategy.”

As the first company to offer autologous adult stem cell collection and banking services to the general adult population, NeoStem works exclusively with adult stem cells, not embryonic stem cells. NeoStem collects adult stem cells from peripheral blood, thereby avoiding bone marrow aspiration collection techniques which must usually be performed under general anesthesia. NeoStem has also entered into a number of R&D projects through the acquisition of licensed technology that identifies and isolates VSELs (very small embryonic-like stem cells).

Since adult stem cells are already being used in clinics around the world for the treatment of a wide variety of diseases and injuries, and since a number of proprietary adult stem cell products are already in clinical trials in the U.S., it would seem to be only a matter of time before FDA approval is attained and such adult stem cell therapies are legally and widely available within the United States. When that happens, the U.S. could become the adult stem cell “Mecca” of the world.

“Potency” is one of the most important properties of a stem cell, and a measure of the cell’s ability to differentiate into various types of tissue. As one of the highest forms of potency, second only to totipotency, “pluripotency” is a coveted feature reserved only for embryonic stem cells and iPS (induced pluripotent stem) cells. Safety and efficacy are also of the utmost importance, however, and pluripotency is well known to be associated with specific risks, especially the formation of teratomas, which are a unique type of tumor.

In the latest issue of the journal Nature, two leading scientists in the stem cell field, Drs. Rudolf Jaenish and Christopher Lengner, both of the Massachusetts Institute of Technology, offer a striking visual illustration that compares the pluripotency of embryonic stem cells with the pluripotency of laboratory-generated cells that are derived from non-embryonic sources, such as the iPS (induced pluripotent stem) cells that are reprogrammed from adult skin cells.

Embryonic stem cells are known not only for the ethical dilemmas that they present, but also for a long list of scientific problems which include difficulty of isolation, biological and chemical contamination, genetic mutation, a lack of controllability during differentiation and, by definition, the ability to form those very specific types of tumors which are known as teratomas. Indeed, as depicted in Drs. Jaenish’s and Lengner’s illustration, teratoma formation remains one of the universally accepted criteria by which pluripotency is defined and empirically determined, even for cells which are not of embryonic origin, such as the iPS cells. Created through such techniques as nuclear transfer, genetic reprogramming and cellular fusion, ordinary adult somatic cells which are not stem cells have been induced to behave with a pluripotency that resembles that of embryonic stem cells, but which circumvents the ethical controversy surrounding embryonic stem cells, by avoiding the use of embryos altogether. These cells, such as the iPS cells, may have solved the ethical controversy, by entirely circumventing the need for embryonic stem cells, but these newly derived pluripotent cells do not solve the medical problems and risks that are associated with teratoma formation, since such cells, by definition, still cause the formation of teratomas and this is still how pluripotency is defined and identified. If a cell forms a teratoma, then it is recognized to be a pluripotent stem cell – whether of embryonic origin or of non-embryonic origin, such as the iPS cells.

Adult stem cells, by contrast, do not form teratomas since they are not pluripotent but instead are, at best, “multipotent”, and as such are well understood to be “lineage-restricted” in their differentiation ability. While such a lack of pluripotency has, in the past, been erroneously seen as an undesirable feature of adult stem cells, it is now recognized as being highly advantageous for a number of reasons which include greater controllability in the differentiation process and no risk of teratoma formation, among other advantages of adult stem cells.

The entire fields of tissue engineering and regenerative medicine are founded upon properties of cellular potency, but not all stem cells are created equal, and a wide spectrum exists across which their properties may be ranked. The specially featured illustration by Drs. Jaenish and Lengner in the latest issue of Nature is already recognized as offering a new and updated set of guidelines for scientists in the field, and a free copy of the illustration may be downloaded at the journal’s website, www.nature.com.

A team of researchers led by Dr. Douglas Melton of the Harvard Stem Cell Institute, in collaboration with researchers at the Howard Hughes Medical Institute, have successfully transformed mature cells in mice into a different type of cell.

The research, which was published today in the online journal Nature, involves the reprogramming of a cellular “identity switch”, which is a type of master control for determining which genes in the cell are activated and which remain inactive. The findings are the first of their kind to be conducted in vivo, with the transformation of ordinary pancreatic cells into the more specialized beta islet cells, which are the cells that produce insulin.

Such research represents a further step in the ongoing effort by many scientists to avoid embryonic stem cells and their ethical dilemmas, by working with pluripotent stem cells from non-embryonic sources. Earlier studies with iPS (induced pluripotent stem) cells, for example, used ordinary skin cells from adults that were reprogrammed into a more primitive state, from which they could then be directed to develop into various types of tissue, at least theoretically. One of the problems encountered with the iPS cells, however, is the difficulty of controlling their differentiation into the desired, specialized tissue. This latest discovery, however, changes a mature cell into another mature cell without having to revert back to a primitive cell as an intermediate stage.

Using mice in which the beta islet cells had been destroyed, Dr. Melton’s team injected the pancreas of the mice with a viral “vector” that delivered 3 genes into the ordinary pancreatic cells, which 3 days later were found to have been converted into the insulin-producing beta islet cells. After a week, over 20% of the cells had begun producing insulin. The newly formed cells were identified as beta islet cells both morphologically (in structure) as well as functionally. According to Dr. Richard Insel, executive vice president of research at the Juvenile Diabetes Research Foundation, this research represents “an amazingly efficient effect”, much more so than that seen from iPS cells thus far.

Dr. Melton has a personal interest in diabetes, and has been a leading researcher in the field since 1993, when his infant son was diagnosed with Type 1 diabetes. However, scientists are quick to observe that these findings have a wide range of implications which extend far beyond diabetes. Researchers at Stanford, for example, are currently studying applications of the same procedure with liver cells. Indeed, the findings mark an important achievement in understanding the molecular signals that are involved in the reprogramming of cells, which is relevant to the treatment of virtually every type of disease.

Following experiments with mice, Stanford University scientists have announced that stem cell therapies which use human embryonic stem cells (hESCs) have a high probability of failing because of immune rejection. In these studies, mice that were injected with hESCs exhibited an immune response which is at least as severe as that triggered by organ transplantation. Consequently, all the transplanted stem cells were killed by the immune system within a week. The Stanford researchers used molecular imaging technology to monitor the hESCs after injection, which revealed that the hESCs began dying within a week of injection and were completely dead by 10 days. When more hESCs were subsequently injected, they were found to die much more quickly, within 2 to 4 days, due to the already fully activated level of the immune system defense response. Even when the animals were given tacrolimus and sirolimus, two mediations that are commonly used to suppress an immune response, the hESCs lasted 28 days before dying but were still rejected and killed by the immune system. Additionally, in all cases, the overall health of the animals continued to deteriorate, and the researchers were not able to determine any benefit from an increase in time before all the hESCs were eventually destroyed.

The U.S. FDA (Food and Drug Administration) has not approved the use of hESCs as a medical therapy, primarily because of the danger of teratomas, which are a well established risk of hESCs. A teratoma is a specific type of tumor which contains cells from all 3 germ layers of the body, which have often differentiated into specialized tissue such as teeth, hair and organs, and which therefore make these tumors particularly hideous and dangerous. The ability of embryonic stem cells to form teratomas is, in fact, the defining trait of embryonic stem cells, and the ability of a cell to form a teratoma remains the universal laboratory test by which embryonic stem cells are identified: namely, if an unknown cell is found to form a teratoma in the laboratory, then it’s an embryonic stem cell, whereas if it doesn’t form a teratoma, then it’s not an embryonic stem cell. Teratoma formation, however, is certainly not the only risk posed by embryonic stem cells, and once again we are now reminded of the dangers of immune rejection that are inherent in embryonic stem cells. Adult stem cells, by sharp contrast, do not pose any risk of teratoma formation, and some types of adult stem cells, such as mesenchymal stem cells (MSCs), are known to be “immune privileged”, meaning that they do not trigger an immune response.

According to Dr. Joseph Wu, a Stanford radiologist who led the recent research, these findings, which reveal such a strong immune rejection of embryonic stem cells, constitute “a reality check”.

The biotech company Advanced Cell Technology, Inc., which develops a variety of stem cell therapies, has entered into another licensing agreement with BioTime Inc., which is also a major player in the stem cell field. Although the agreement was struck on August 15th, the companies made the announcement today. This agreement is not the first of its type between the two organizations, which have worked together before in patent licensing agreements. As before, this agreement involves a susidiary of BioTime Inc., known as Embryome Sciences.

BioTime is headed by CEO Michael West, who was formerly with Advanced Cell Technology. Under the terms of the new agreement, Embryome Sciences will receive worldwide rights to the patent that is owned by Advanced Cell Technology, in exchange for a $200,000 licensing fee which Embryome Sciences must pay, as well as a 5% royalty on sales and 20% of fees for sublicensing to a third party, with a royalty cap of $600,000. In a previous, recent licensing agreement that was announced on August 11th, Embryome Sciences licensed the technology for producing embryonic progenitor cells from Advanced Cell Technology, for which Embryome Sciences paid a $250,000 licensing fee plus an 8% royalty on sales, with a royalty cap of $1 million.

Unlike the previous licensing agreement, however, the current agreement involves patented technology for the transformation of skin and other adult human cells into pluripotent cells which are able, through the manipulation of cellular controls, to differentiate into various types of tissue that are found throughout the human body.

As an advanced form of peripheral artery disease, critical limb ischemia (CLI) results in approximately 100,000 amputations every year in the United States alone. It is often seen in diabetics and is a major cause both of morbidity and of mortality, with approximately 20 to 45% of all patients requiring amputation, after which death within the first year is estimated to be as high as 45%. The quality of life in such patients is extremely low, compared by some doctors to that of terminal cancer patients.

In the past, treatment options for patients with CLI have been extremely limited, and without notable success. Now, however, the company Medistem, Inc., has developed a treatment for CLI which uses the powerful endometrial regenerative cells (ERCs) which Medistem brought to international attention last year.

Previous, independent clinical trials have shown some improvement in CLI patients who received autologous (in which the donor and recipient are the same person) stem cells that were either derived from the patient’s own bone marrow or mobilized from peripheral blood. Similarly, ERCs, which are adult stem cells that are derived from menstrual blood and which resemble mesenchymal stem cells (MSCs), are believed to be associated with endometrial angiogenesis and have been shown to have powerful angiogenic properties. Additionally, ERCs contain an exceptionally high level of growth factors and are notable for a wide variety of other impressive properties which include their ability to inhibit the inflammatory response, their ease of expandability in large quantities without incurring a loss of differentiability nor any karyotypic abnormalities, and the fact that ERCs are highly immune privileged and therefore do not trigger immune rejection.

In the recently published study, which was led by the vascular surgeon Dr. Michael Murphy, a group of mice was divided into 8 who were treated for CLI with ERCs, and 8 mice who served as the “controls” and whose CLI was untreated. Following ligation of the femoral artery and its branches in each of the mice, which thereby induced CLI, the 8 mice who were chosen to be treated were each administered approximately 1 million ERCs intramuscularly. By day 14, necrosis was observed in the legs of the 8 “control” mice, who did not receive the ERCs, while the 8 mice who were treated with the ERCs still had intact limbs. Especially striking was the absence of any immune rejection of the ERCs, despite the fact that these were human stem cells, which were administered to mice which had fully competent immune systems.

It has already been known for some time that MSCs exhibit immune modulatory properties, both in vitro and in vivo. For example, the company Osiris Therapeutics is currently involved in Phase III clinical trials with allogeneic MSCs that are derived from bone marrow and which are currently being tested as treatment for two diseases, namely, graft-versus-host disease, and Crohn’s disease. Now, in the study conducted by Dr. Murphy, Medistem has demonstrated the ability of ERCs to prevent limb loss in an animal model of critical limb ischemia, even with animals that were fully immune competent. ERCs are therefore believed to offer what is known as cytokine mediated angiogenesis, which thus far has been especially effective as a therapy for CLI in this particular animal model.

Medistem, which has pioneered the development of ERCs as a “universal donor” product, has received global recognition for its work in this field, including the “Publication of the Year” award for 2007, recognizing its discovery of ERCs, which was awarded to Medistem at London’s Royal Society of Medicine in early 2008. Medistem is now seeking to use ERCs as a therapy for patients who are at risk of amputation due to CLI.

Researchers at the Harvard Stem Cell Institute (HSCI) have reported the creation of twenty stable cell lines from patients with genetic diseases that include Type I diabetes, Parkinson’s disease, Hungtinton’s disease, Down Syndrome, and two types of muscular dystrophy. Although the cell lines resemble stem cells in their pluripotency, none of the cell lines were created from stem cells.

Instead of stem cells, the scientists used iPS (induced pluripotent stem) cells, which are mature cells, usually taken from the skin or blood of adults, that have been reprogrammed to revert to a more primitive state that resembles a stem cell. From these iPS cells, new cell lines were specifically created for various genetic disorders. According to Dr. George Daley, a professor in Harvard’s Medical School, senior author of the paper in which the announcement was made, and a member of the executive committee of the HSCI, “This has really been one of the goals of stem cell biology for many years, to be able to produce customized disease-specific lines for different patients.”

Other scientists around the world who are studying these various diseases will soon be able to order shipments from the HSCI of these disease-specific cell lines. Indeed, “patient-specific” iPS cells, which are reprogrammed cells derived from specific patients, allow for an individually tailored study, in the laboratory, of the unique characteristics of a particular person’s disease, thereby opening up the opportunity for therapies that are customized to each individual person. Dr. Konrad Hochedlinger, also a professor at Harvard Medical School, whose lab contributed to the Lesch-Nyhan syndrome cell line in the project, has referred to the “iPS trick” as something that is changing the face of stem cell research, by genetically reprogramming human, non-stem cell, cells to behave as though they were stem cells.

In July of this year, a new iPS Core Facility was created at the Harvard-affiliated Massachusetts General Hospital, where the disease-specific iPS cell lines will be deposited not only for storage but also for production on a larger scale, in order to accommodate distribution to the scientific community. According to Laurence Daheron, manager of the iPS Core Facility, the iPS cell lines will be available free of charge for HSCI members and collaborators, although non-HSCI members and biopharmaceutical companies will be required to pay a fee in order to cover the cost of expansion of the iPS cell lines.

The creation of the iPS cell lines, and the establishment of the Core Facility at Massachusetts General Hospital, has vast implications not only for stem cell therapies involving the particular diseases under consideration, but also for the stem cell field and for cell biology in general.