The biotech company Genzyme has received approval from the FDA for the marketing of its proprietary adult stem cell stimulating product, Mozobil, which is a novel, proprietary small-molecule CXCR4 chemokine receptor agonist. When used in combination with G-CSF (granulocyte-colony stimulating factor), Mozobil has been shown to increase the number of stem cells circulating in the peripheral blood by mobilizing hematopoietic stem cells in the bone marrow and stimulating the cells to migrate into the bloodstream for easier collection and subsequent autologous transplantation.

According to John DiPersio, M.D., Ph.D., a professor at Washington University in St. Louis, “Mozobil is an important advancement in the treatment of patients with certain types of cancer who require a stem cell transplant. This product should become an integral part of the treatment regimen for transplantation because of the benefits it offers to patients, physicians and transplant centers.”

In order to receive an autologous (in which the donor and recipient are the same person) adult stem cell transplant, each patient must be able to donate a minimum of 2 million stem cells per kilogram of body weight. After being collected, isolated and expanded, the adult stem cells are then administered to the patient as part of the therapy. For some patients, the collection process alone can take hours, spread out over multiple days, and for those patients who are not able to mobilize enough stem cells for the collection, the transplant is not possible. By mobilizing a patient’s endogenous stem cells and by stimulating the stem cells to migrate from the bone marrow into the bloodstream, Mozobil facilitates the therapeutic adult stem cell process, especially for patients who might not otherwise be able to receive such a therapy at all.

According to Joseph Lobacki, senior vice president and general manager of Genzyme’s transplant and oncology division, “Mozobil is an exciting and innovative new treatment that expands Genzyme’s contribution to the field of hematology and oncology. We look forward to strengthening our partnership with the blood and marrow transplant community to make this product broadly available to patients who are facing transplantation procedures for non-Hodgkin’s lymphoma or multiple myeloma.”

Approximately 55,000 hematopoietic stem cell transplants are performed each year globally for multiple myeloma, Hodgkin’s and non-Hodgkin’s lymphoma, for which Mozobil is expected to be used in the majority of such cases. Peak annual sales of Mozobil are projected to reach $400 million. Genzyme has also submitted applications to the respective regulatory agencies in Europe, Australia and Brazil for marketing approval of Mozobil, and additional applications in up to 60 countries are planned.

Founded in 1981, Genzyme now has more than 10,000 employees around the world with revenues in 2007 of $3.8 billion. With products and services available in nearly 90 countries worldwide, Genzyme focuses on the treatment of rare inherited disorders, kidney disease, orthopedics, cancer, transplantation, and diagnostic testing. In 2007, Genzyme was awarded the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation.

In what can hardly be considered a surprising document, the Roman Catholic Church has released a new publication addressing matters of bioethics. Referred to simply as “Dignitas Personae” (“The Dignity of the Person”), a shortened version of the full title which is “Dignitas Personae – Instruction on Certain Bioethical Questions”, the 23-page-long document takes a serious look at recent advancements in biomedical science and the resulting ethical dilemmas. The purpose of the document is to offer guidance not merely to Roman Catholics, but “to all who seek the truth”, as is stated on page 2 of the Introduction.

Although this document itself is new, its intrinsic message is not. The stance reiterated throughout all 23 pages is the same thesis that is always promoted by the Catholic Church, namely, that “the Magisterium of the Church has constantly proclaimed the sacred and inviolable character of every human life from its conception until its natural end.” (p. 10) It should therefore come as no surprise to anyone, whether or not one agrees with such a stance, that this is the basic premise of the document. According to the website of the United States Conference of Catholic Bishops, the new Vatican document offers instruction “on ethical issues arising from biomedical research” and “provides guidance on how to respect human life and human procreation in our heavily scientific age.” In fact, the paper is in may ways an updated, modernized version of another Vatican “instruction” document, “Donum Vitae” (“The Gift of Life”), which was issued in 1987 under the pontificate of John Paul II, and to which “Dignitas Personae” makes repeated reference. “Instruction” documents, which are not authored directly by a Pope but are approved by a Pope, are not to be confused with papal encyclicals, which are authored directly by a Pope, such as “Veritatis Splendor” (1993) and “Evangelium Vitae” (1995), both of which were personally written by Pope John Paul II, and the more controversial “Humanae Vitae” which was written in 1968 by Pope Paul VI, all of which reinforce the same themes as “Donum Vitae” and “Dignitas Personae”.

Critics of the Vatican and of Roman Catholic Church policy often point out, and justifiably so, previously erroneous stances taken by the Church in the past, most notably in the field of science. One of the most egregious examples involved the trial of Galileo in 1633 by Pope Urban VIII, during which Galileo was found guilty of promoting the “heretical” view of a heliocentric solar system (in which the sun, not the earth, is located at the center), for which Galileo was imprisoned and then sentenced to house arrest for the remainder of his life. Only in 1992 did the Church finally and officially exonerate Galileo, when Pope John Paul II expressed public regret for the incident that had occurred over 3-and-a-half centuries earlier. As Church critics will also point out, the legal body which interrogated and imprisoned Galileo, for the “heresy” of defending what is now known to be a scientific fact, was none other than the ecclesiastical tribunal infamously known as the “Inquisition” and which today is known by the name of “The Congregation for the Doctrine of the Faith” – the very same Church institution which issued “Dignitas Personae”. Such facts, coupled with the highly publicized priest scandals in recent years, have not given the Roman Catholic Church a very admirable public-relations image. Nevertheless, there do exist modern bioethical dilemmas, which are the result of recent breakthroughs in medical science, and there are people throughout the world who do seek guidance and moral direction on such topics. Since very few other organizations are issuing formal “doctrinal instruction” in such matters, documents such as “Dignitas Personae” are received with widespread and genuine interest. Whether or not the instruction offered by such a document will ever actually be followed, however, is yet to be seen.

It has commonly been observed that the Vatican does not update its official doctrine casually nor hastily. Nevertheless, although it took nearly 4 centuries for the Church to apologize for the Galileo incident, it has taken only 21 years for “Donum Vitae” to be updated with “Dignitas Personae”. Indeed, the relatively swift and timely release of “Dignitas Personae” at this particular moment in history is seen by many as an indication of the urgency and the importance with which the Church views the bioethical problems that are the focus of the document.

Contrary to popular opinion, the Roman Catholic Church is not against stem cell research in general, but, more specifically, is only against embryonic stem cell research. Such objections are not random nor without basis, since the derivation of embryonic stem cells requires the destruction of an embryo, which is an act that most theologians, Christian and otherwise, believe to be morally and ethically wrong. By sharp contrast, however, as is clearly stated in “Dignitas Personae”, the Roman Catholic Church is strongly in favor of research and therapies that involve adult stem cells. As stated on page 19 of the document, “Research initiatives involving the use of adult stem cells, since they do not present ethical problems, should be encouraged and supported.” Even with research and therapies that fall exclusively within the adult stem cell realm, however, the authors of the document are clear in their emphasis that, “Such use should be characterized by scientific rigor and prudence, by reducing to the bare minimum any risks to the patient and by facilitating the interchange of information among clinicians and full disclosure to the public at large.” The central argument of the document, in effect, is one that calls for serious ethical consideration of all aspects of biomedical science, not only in those fields that involve the use of stem cells.

Of the 23 pages that constitute “Dignitas Personae”, the topic of stem cells is only specifically addressed on pages 18 and 19. The rest of the document examines other issues, such as in vitro fertilization, the cryopreservation of embryos and oocytes, “embryo reduction”, intracytoplasmic sperm injection (ICSI), forms of interception and contragestation, the manipulation of embryos and of “the human genetic patrimony”, reproductive and therapeutic cloning, gene therapy and germ line cell therapy, transgenic experimentation and hybrid cloning with human somatic cellular nuclei that are reprogrammed within nonhuman mammalian oocytes, among other topics – all within the context of “anthropological, theological and ethical aspects of human life and procreation.” Following the Introduction, the paper is divided into 3 sections which progress systematically through successive logical developments that build upon what the authors describe on the first page as “principles of Christian anthropology”. In authoring this document, the Congregation for the Doctrine of the Faith assures its readers that it has “consulted numerous experts with regard to the scientific aspects of these questions”.

The paper is not meant to be an exhaustive scientific treatise on all aspects of modern medicine, and some topics are conspicuous by their absence, such as, most notably, iPS (induced pluripotent stem) cells. Teratomas are also never explicitly mentioned, per se, although there are many scientists throughout the world who seriously question whether embryonic stem cells can ever be usable as a safe and viable medical therapy due to the innate tendency of embryonic stem cells to form the specific type of tumor known as a teratoma. Since adult stem cells do not carry any risk of forming teratomas, and since adult stem cells are already being used as clinical therapies throughout the world, there are many scientists who do not advocate embryonic stem cell research but who do advocate adult stem cell therapies, for reasons that have nothing to do with religion, theology or ethics, but which have everything to do with principles of sound science and with the practical realities of medicine. Nevertheless, “Dignitas Personae” boldly addresses all of the uncomfortable, most emotionally charged and sensitive ethical issues that are unavoidably entangled in stem cell research, and which most scientists and researchers diplomatically go out of their way to try to avoid.

Theologians are not the only people who believe that many aspects of modern science “call for attentive moral discernment”, as the authors of “Dignitas Personae” assert. To borrow another phrase from the Vatican document, for many people there still remains the nagging, seemingly unresolved question of whether embryonic stem cells might possibly be something more than just “biological material”. Indeed, classes and entire departments in “bioethics” are springing up in law schools throughout the U.S. with increasing popularity, a prime example of which was the founding in 2005 by Harvard Law School of an entire center, “The Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics”, precisely to provide a forum in which legal experts can debate and address, and formulate legislative policy on, such issues. With an increase in the number and types of new therapeutic modalities that are developed within the various medical specializations, the number and types of litigation are also expected to increase, and a new generation of lawyers who specialize in bioethics is currently being groomed to meet the future legal needs of a world that will be dramatically unlike the world for which current laws were designed. Even though doctors and scientists may not be formally addressing matters of medical bioethics, the lawyers are. If not for an interest in ethical reasons per se, then perhaps for an interest in legal ramifications, the scientific and medical communities might wish to join the conversation.

Outside of medicine, in many other branches of science, such as with the growing concern over ecological consequences of combustible fuel, a strong sense of ethics is encouraged and applauded. Even outside the realm of science, such as with the recent global economic crisis, there is a loud outcry for serious legal reform requiring transparency, responsibility, accountability and oversight, both at the corporate and at the individual levels. Similarly, “Dignitas Personae” calls for nothing more nor less than the same type of objective ethical standards to be applied to medical science. Without “an ethical point of reference”, that is, without some sense of prudence, without concern for the safety and dignity of others, and without a high degree of personal responsibility and accountability built into the system, the authors of the document warn that it is all too easy for people to “surrender to the logic of purely subjective desires and to economic pressures which are so strong in this area” (p. 9), especially in the potentially lucrative field of regenerative medicine.

As stated on page 2 of the Introduction of “Dignitas Personae”, the authors seek “to offer a word of support and encouragement for the perspective on culture which considers science an invaluable service to the integral good of the life and dignity of every human being.” As such, the authors make a compelling argument for “the ethical use of science”. In clear and direct language, “Dignitas Personae” specifically “calls everyone to ethical and social responsibility for their actions.” (p. 6) Although many people will not agree with the particular details of the stance that is promulgated by this particular document, most people will still agree that at least an open and healthy debate on such topics might be more productive than a systematic attempt to ignore the topics categorically. The authors also recall the words of Pope John Paul II, who made an “appeal to the conscience of the world’s scientific authorities and in particular to doctors”, but in “Dignitas Personae” it is everyone – patients and doctors alike – who are summoned to an honest and critical examination of conscience.

Regardless of one’s religious affiliation, and whether or not one has any religious affiliation at all, most if not all people, especially scientists, would probably agree to an ethical and responsible use of the modern powers of science and technology. The precise definitions of “ethical” and “responsible”, however, are currently the subject of widespread disagreement. One topic over which there is no disagreement nor debate at all, however, is the fact that embryonic stem cells cause teratomas, since this is, by definition, the gold standard by which pluripotency is identified in laboratories throughout the world. For anyone who may seek “guidance” in the field of stem cells but who prefers to avoid theological inquiry altogether, such people need look no further than the topic of teratoma formation for one of the many exclusively scientific reasons to be extremely cautious when considering embryonic stem cells as a medical therapy. Since adult stem cells are already in use in clinics around the world, as real therapies in the treatment of real human beings with a wide range of real diseases and injuries, and since adult stem cells do not pose any of the numerous medical risks that embryonic stem cells pose – such as biological contamination and genetic mutation in addition to teratoma formation, among other problems – the use of adult stem cells has already been proven as both legitimate and responsible science. Religion and politics aside, in the use of adult stem cells, there is no discrepancy between science and ethics.

At 5 years of age, Monty the golden retriever suffered with hip and elbow dysplasia as well as arthritis and immobilizing pain. When other types of treatments failed to help, Monty’s owners Steve and Beth Armogida decided to try stem cell therapy. Their veterinarian, Dr. Charisse Davidson of the CM Surgical Specialty Group in Pasadena, California, used adult stem cells harvested from Monty’s own body fat to treat the dog. As Dr. Davidson explains, “The stem cells aren’t a miracle, but they’re science and they’ve been shown to help in about 77% of cases.” Dr. Davidson removed some of the dog’s fat tissue in a simple procedure and shipped the tissue to Vet-Stem’s laboratories in San Diego where the stem cells were isolated, expanded and then returned to Dr. Davidson who administered the stem cells to the dog at the point of injury. According to Julie Ryan Johnson, DVM, of Vet-Stem, the stem cells “signal other cells to come in, which is an interesting concept called trophism. They’re basically signalling the body to send in other defense mechanisms to come in and clean things up.” Within six months after the treatment, Monty was free of the pain and arthritis and dysplasia that had previously plagued him.

Another successful example involved a 12-year-old golden retriever who couldn’t even stand up prior to receiving adult stem cell treatment, but who was restored to painfree mobility afterwards. According to the dog’s owner, Pat Glazier, “She was like a new dog. She can stand up by herself, she comes when she’s called she can go up and down stairs.”

Veterinary stem cell therapy has advanced most aggressively with race horses, since these are the “patients” who have been in most urgent need of such a therapy, and more than 3,000 horses have been treated with their own adult stem cells thus far. Since embryonic stem cells pose a number of serious risks, not the least of which is the formation of teratomas, which are a particular type of tumor, not only for humans but also for animals, the stem cells that have been used in veterinary medicine are adult stem cells, not embryonic stem cells, and are harvested from each animal’s own body. One of the most notable equine cases involved the treatment of the race horse known as Be a Bono, who suffered an injury which could have ended a highly successful career. Instead, after receiving the stem cell therapy, Be a Bona returned to racing and won more than a million dollars in prize money. As Dan Francisco, the horse’s trainer, explains, “You’re always skeptical. You want to see if it works, somebody has to try it. We did. It worked.” Indeed, adult stem cell therapy offers the first concrete evidence of improvement in the treatment of articular cartilage and tendon injuries to which horse joints are particularly vulnerable. Since such injuries in small animals are less of a life-threatening problem than they are in large animals, adult stem cell therapy has made the greatest and most noticeable difference in the lives of horses and dogs. Nevertheless, at least 19 cats have been treated with their own adult stem cells thus far, along with over 1,000 dogs of varying breeds, and more than three times that many horses. The price of the therapy varies according to the particular type and condition of the animal, but generally falls within the $2,500 to $4,000 range. A number of patents have been issued to biotech companies who are driving the development of innovative technology in this field, a recent example of which is a U.S. patent that was awarded to the South Korean company Medipost for its invention of a biodegradable polymer scaffolding on which mesenchymal stem cells derived from umbilical cord blood are stimulated to regenerate hyaline cartilage.

Like many other animals, Monty the golden retriever is now enjoying the benefits of his own adult stem cell therapy in this rapidly developing field. As Dr. Davidson points out, “Maybe this will set an example for the human world to say, look, we’re having success on dogs, maybe we can have success in people too.”

Cancer stem cells are thought to be the source of some types of primary and recurrent cancers and are characterized by their high degree of potency and self-renewing capacity. In embryonic stem cells and germ cells, properties of self-renewal and pluripotency are regulated by the Oct4A gene, a marker which has been suspected of playing a role in the origin of some cancers. Although a number of key questions still remain unanswered, scientists have now made important progress in understanding how the Oct4A gene might be involved in the development of prostate cancer.

Led by Dr. Paula Sotomayor, researchers in the Department of Urologic Oncology at the Roswell Park Cancer Institute in Buffalo, New York have identified Oct4A in a small subset of prostate cells which were negative for many other types of more conventional cancer stem cells markers, such as markers of luminal epithelial and basal epithelial cell differentiation, including the markers ABCG2, NANOG, CD133 and AMACR. A further subpopulation of the cells expressing Oct4A were also found to co-express the embryonic stem cell marker Sox2, which is a transcription factor necessary for the self-renewal of undifferentiated cells. Yet another subpopulation was found to co-express synaptophysin, while the majority of the Oct4A-expressing cells were found to co-express chromagranin A, both of which are neuroendocrine differentiation markers.

Cells expressing Oct4A have been found in both benign and malignant prostate glands. As one would expect, the amount of Oct4A-expressing cells that are present in the gland is directly correlated with the Gleason score, which is a measure of glandular size and microscopic appearance of the prostate, with lower scores being associated with smaller, more tightly packed glands, whereas higher scores indicate a more loosely dispersed glandular structure.

Oct4A is one variant, along with Oct4B, of the Oct4 marker, and the precise molecular mechanisms governing these variants are yet to be determined. As the authors describe in their publication, “rare cells that express Oct4 were identified in several somatic cancers, however, the differential contributions of the Oct4A and Oct4B variants were not determined.”

Nevertheless, with the discovery that cells expressing Oct4A are present in cancerous prostates in numbers that correlate with the severity of the malignancy, scientists are one step closer to understanding this particular form of cancer. Further investigations will be focused especially on those various subpopulations of the cells that co-express the neuroendocrine differentiation markers chromagranin A and synaptophysin, both of which offer new and important pieces in the puzzle.

Scientists have finally determined the answer to a question that has been on the minds of most stem cell scientists for years: namely, where, exactly, in precise anatomical terms, are bone marrow stem cells produced? Thanks to the invention of new imaging technology, this mystery has now been solved.

In collaboration with several of the support facilities at the Stowers Institute in Kansas City, Missouri, the Linheng Li Lab led the development of the new “ex vivo imaging of stem cells” (EVISC) technology, which monitors in real time the dynamic behavior of stem cells. Using the EVISC, scientists were finally able to observe and track the homing of hematopoietic stem cells after transplantation in mice, which led to the discovery of the newly identified bone marrow niche. This is not the first time that the Linheng Li Lab has pioneered such breakthroughs, as the Lab was already renowned for its discovery in 2003 of the hematopoietic stem cell (HSC) niche, which was reported by Zhang et al. in Nature.

Now, according to Dr. Yucai Xie, predoctoral researcher and a coauthor of the most recent paper, “Using the EVISC technology, we were able to confirm our 2003 findings that HSCs tend to home to the inner bone surface. Additionally, we were able to resolve a debate in the field about whether the bone-forming niche or the blood-vessel-forming niche actually nurtures HSCs. Surprisingly, we revealed that the inner bone surface forms a special zone that includes both osteoblastic and endothelial components. This HSC zone maintains HSCs in their resting state and promotes HSC expansion in response to bone marrow stressors, such as irradiation.”

Scientists have long wondered about the precise location of the HSC niche, as well as details about the nature of the microenvironment of this niche, a better understanding of which would assist with the development of more effective bone marrow transplants by giving scientists and physicians greater control over the entire process by which stem cells from bone marrow are harvested and expanded. According to Dr. Winfried Wiegraebe, director of the Stowers Institute’s Advanced Instrumentation and Physics division, who assisted with the famed two-photon experiments, “The new technique developed in this study may have a variety of applications including monitoring other types of cells in low population numbers in vivo.” As Dr. Linheng Li adds, “EVISC technology will allow us to study HSC lineage commitment in vivo. Furthermore, we will be able to use this technology to study leukemia and other cancer stem cells to better understand whether they use the same or different niches that normal stem cells use, and even to evaluate drug resistance and treatment responses. This is an exciting new avenue for our work.”

Additional study and experimentation are now planned that will further examine the characteristics and processes that are unique to this niche. The mere fact that the inner bone surface actually forms a separate, distinct, unique zone with both osteoblastic and endothelial components, in which HSCs are maintained in their resting state and expanded in response to bone marrow stressors, is in and of itself a discovery with far-reaching applications to the field of regenerative medicine.

Scientists at the University of Minnesota have demonstrated that bone marrow-derived stem cells offer a novel treatment option for epidermolysis bullosa (EB), a rare disorder that is characterized by severely fragile skin that blisters on touch, to an extent similar to third degree burns. In infancy the disease is often fatal while in childhood and adulthood a recessive dytrophic form of EB (known as RDEB) usually results in years of painful blistering and mutilating scarring. The cause of the condition is a genetic inability of the body to produce an adequate amount of collagen type 7 (col7) protein, which is an essential component of the anchoring fibrils that connect mucosal tissue in the gastrointestinal tract and cutaneous membranes to the dermis of the skin. A lack of these fibrils results in a hypersensitive dermal-epidermal connection, to such a degree that any movement which causes even the slightest friction, such as eating, walking, or the rubbing of clothing, creates too much stress between the skin layers which results in blisters and sores.

Children with RDEB develop a number of complications which often include squamous cell carcinoma. Currently there is no cure for the disease, and even the best palliative care is grossly inadequate in alleviating the suffering of the patients.

According to Dr. Jakub Tolar of the University of Minnesota, who led the study, “We have been looking into stem cells as viable treatment options for the correction of conditions such as epidermolysis bullosa, because stem cells can produce extracellular matrix proteints. In this condition, the skin, the largest organ in the body, can significantly benefit from a renewable source of healthy cells that can help improve the connection between the dermis and epidermis and strengthen the skin against everyday stresses.”

Dr. Tolar’s team used a mouse model from which bone marrow cells infused with RDEB were found to increase production of the col7 protein and hence the formation of anchoring fibrils, which slowed the progression of the disease and improved survival in the mice. In addition to the RDEB-infused cells, bone marrow cells were enriched with hematopoietic and progenitor cells and were also found to target the diseased areas of the skin where they increased col7 protein and the production of anchoring fibrils, thereby preventing the formation of blisters. Survival time was increased to ten days in mice who received both the cells that were treated with RDEB and the cells that had been enriched with hematopoietic and progenitor cells, as opposed to 6 days in mice that received only the RDEB-treated but not the enriched marrow cells, and 5.6 days in mice that received untreated cells. Of the 20 mice that received both the treated and the enriched cells, 3 mice improved so significantly that they outlived the treatment period, wheras untreated RDEB mice usually die within two weeks. Each surviving mouse also exhibited dramatic improvement and healing of old blisters.

As Dr. Tolar explains, “Our data provide the first evidence that a selected population of marrow cells can connect the epidermis and dermis in a mouse model of the disease and offer a potentially valuable approach for the treatment of human RDEB and other extracellular matrix disorders. These results provide proof-of-principle of bone marrow transfer to repair the basement membrane defect in RDEB, and they warrant a clinical trial to assess the safety and efficacy of treatment of human RDEB by means of hematopoietic cell transplantation.”

Bone marrow stem cells are already widely known for their therapeutic properties, and this study demonstrates the systemic benefits of these cells in treating disorders that specifically involve defects of the extracellular matrix. New studies are currently in progress to further test the capacity of bone marrow-derived stem cells to produce the various proteins that constitute the highly specialized microenvironment of the extracellular matrix.

Approximately 50 births in one million are diagnosed with EB, which has been documented in all major ethnic groups throughout the world.

The findings were published in the online edition of Blood, the official journal of the American Society of Hematology.

An eleven-year-old golden retriever named KC is now running and jumping around actively and painlessly, as any dog half his age might do. Merely 3 months ago, however, KC could not even walk without difficulty.

According to the dog’s owner, Krista Moyes, “He likes to swim and run and he’s very active. I just wanted to do whatever I could. He was having a hard time getting up in the morning and really wasn’t walking at all on his back leg. “KC was suffering from a combination of injuries and age-related arthritic joint degeneration, and because of the dog’s advanced age, surgery was not a viable option. Ms. Moyes therefore took KC to a veterinary specialist in Sonora to explore alternative options.

According to veterinarian Dr. Lillian Rizzo, “We had some chronic old injuries, some chronic arthritis, decreased range of motion and pain in that right leg.” Consequently, Dr. Rizzo suggested an adult stem cell therapy which has shown great success in treating a variety of tendon, ligament and joint injuries in small animals such as cats and dogs and also in large animals such as horses. Developed by the company Vet-Stem, the procedure is fast, simple and minimally invasive, requiring only that the vet extract some fat tissue from the animal which is then sent to Vet-Stem where technicians isolate and expand the stem cells from the fat, and return the cells to the vet who injects them directly into the site of injury. As Dr. Rizzo explains, “I send the fat to [Vet-Stem] and they turn it around back to me in the form of an injection syringe within 48 hours. I concentrate the stem cells at the site of injury and then the stem cells mediate inflammation and repair. The injury is to the joint cartilage and that’s really the only thing that can do that. The medications can help with pain and support but the stem cells actually rebuild the damaged joint cartilage.” Another advantage to the therapy is that results are usually seen so quickly that pain medication is no longer needed once the adult stem cell therapy is actually administered.

As any modern, well-informed, scientifically savvy, 21st century patient would do, KC underwent the adult stem cell therapy with eagerness and enthusiasm. According to the dog’s owner, Ms. Moyes, “Two weeks after the surgery I looked at him one day and he was standing on his foot instead of just his toe. I really noticed an attitude change as far as his energy level. He felt better so he was wrestling, carrying on and playing.”

Since Vet-Stem’s therapy uses stem cells that are derived from the animal’s own fat, such stem cells are strictly and exclusively classified as adult stem cells, not embryonic stem cells. Even in animals, as with humans, embryonic stem cells are not available as clinical therapies since embryonic stem cells are inherently very problematic and pose a number of life-threatening risks, including the formation of teratomas which are a type of tumor with very specific, and grotesque, characteristics. Adult stem cells, by sharp contrast, are not scientifically problematic and, most notably, adult stem cells do not carry the risk of teratoma formation nor any of the other dangers which thus far are inextricably tied to embryonic stem cells. It should come as no surprise, therefore, that adult stem cells are already available as viable clinical therapies in the treatment of a wide range of diseases and injuries, for humans as well as for animals, whereas any hope of any clinical therapy ever being developed from embryonic stem cells is at least another decade away, if not further.

As any dog owner can testify, the question has often been posed as to who, exactly, is training whom, in the symbiotic evolution of humans and their canine friends. At least in the case of adult stem cell therapy, perhaps the two-legged species can learn and benefit from the noble example of its four-legged faithful companion.

Scientists at the University of California at Los Angeles have definitively identified both the place and the time at which the human body manufactures blood stem cells: the place is within endothelial cells, and the time is specifically during the period of mid-gestational embryonic development.

Although the basic, general anatomic location within the embryo from which blood stem cells originate had already been identified, no one knew with certainty which specific cell type it is within the embryo that gives rise to the blood stem cells. Two of the leading, competing theories argued that blood stem cells might be created within the endothelium, or perhaps outside of the endothelium in a neighboring location. Now it has finally been proven that the place of origin of blood stem cells is within the endothelium itself.

Scientists at UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research made the discovery using genetically marked endothelial cells, which line the inside of blood vessels, and a “cell fate tracing technique” by which any new cells generated by the endothelial cells could be identified and their paths of migration followed.

According to Dr. Luisa Iruela-Arispe, professor of molecular, cell and developmental biology and director of the Cancer Cell Biology Program at UCLA’s Jonsson Comprehensive Cancer Center, “We genetically traced the endothelial cells to find out what they became over time. In that way, we were able to understand that, within the embryo, endothelial cells were responsible for the generation of blood stem cells. They make blood, they aren’t just the pipes that carry it.”

The finding has broad potential application to the development of new stem cell therapies for blood disorders and for certain types of cancer such as leukemia. Until now, no one has been able to grow blood stem cells outside of the human body without the cells losing their potency, but as a result of this discovery, however, it may now be possible to grow blood stem cells in the laboratory, directly from endothelial cells.

According to Dr. Ann Zovein, a Broad Stem Cell Research Center Training Grant postdoctoral fellow at the California Institute for Regenerative Medicine, “We found that endothelial cells are capable of making blood stem cells within embryonic areas that prevent differentiation into other lineages. In trying to understand how blood stem cells arise from the endothelium, we may learn enough to be able to grow pure, designer blood stem cells outside the human body.”

A further delineation of the time-line during which blood stem cells develop is also an important discovery with far-reaching applications of its own. The fact that endothelial cells manufacture blood stem cells only during a specific period of time during embryonic development, namely, at mid-gestation, has vast implications for any researcher who hopes to mimic the embryonic microenvironment in the lab. Among other variables, for example, cell signaling pathways that exist only during that particular phase of embryonic development play a major role in the self-renewing, non-differentiating nature of the blood stem cells at that stage, which scientists will need to understand in order to recreate such an environment in vitro, which thus far no one has been able to do. As Dr. Iruela-Arispe explains, “Next we need to understand what signaling mechanisms are at work that allow endothelial cells to make blood stem cells. We need to find out how we can program the endothelial cells to make blood stem cells, what’s important in the embryonic blood vessel wall that allows for this phenomenon and whether we can reprogram adult blood vessels to do the same thing.”

Although the discovery was made with mouse endothelial cells, Dr. Iruela-Arispe and her colleagues are now planning experiments with human endothelial cells in order to examine further the cellular and molecular signaling mechanisms behind the formation of blood stem cells.