How does one distinguish between a stem cell and a regular (non-stem cell) somatic cell? For embryonic and other pluripotent stem cells, the test is a straight-forward and globally recognized one: look for the formation of a teratoma (a tumor containing cells and tissue from all 3 germ layers). However, for adult stem cells, which are not pluripotent and which therefore do not form teratomas, the predominant identifying feature is self-renewal. In this manner, through a new procedure that identifies cellular self-renewal in various subpopulations of cells, researchers have now demonstrated that a subset of pancreatic cells, known as acinar cells, behave as adult stem cells. Although the acinar cells are not, technically speaking, adult stem cells in the classical sense of the term, they nevertheless exhibit properties of self-renewal that are normally characteristic of adult stem cells.

The geneticist Dr. Mario Capecchi developed the innovative method of identifying such cells, in collaboration with Dr. Eugenio Sangiorgi of the Catholic University of Rome. In 2007, Dr. Capecchi shared the Nobel prize in Physiology or Medicine with Sir Martin Evans and Dr. Oliver Smithies, “for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells”, work which directly resulted in the world’s first genetically engineered “knockout mouse” and which consequently spawned new fields of research into a broad range of genetic diseases.

As Dr. Sangiorgi explains, “We can only infer that a cell really is a stem cell by observing its behavior. Together with Professor Capecchi, we had already designed in the past a novel way to mark the stem cells in a tissue: a sort of little flag, capable of helping us to effectively label the cells we were looking for. In order to understand that these are really stem cells, we need only to wait. A normal cell is sooner or later destined to die. A stem cell, instead, retains its capacity to renew itself and replicate. Thus, if we can still observe, many months later, that a cell is still alive, that means it is indeed a stem cell – or a cell derived directly from the division of a stem cell.”

Led by Dr. Capecchi, the researchers employed the use of a piece of DNA as a “molecular switch” that produces a fluorescent protein when activated, which occurs only under specific conditions. According to Dr. Sangiorgi, “So far, a stem cell was really looked upon as a sort of General, in charge of all the other cells, but really doing nothing: an undifferentiated cell, but with no specific task other than generating new tissue. Acinar cells, on the other hand, despite being proved stem cells, have a well-defined task in the pancreas. They are like soldiers doing their job, but also capable, when necessary, of taking over the reins of the government.”

More precisely, the procedure involves a method known as Bmi1 (the polycomb ring finger oncogene) lineage tracing, through which the scientists demonstrated that the self-renewing pancreatic acinar cell subpopulation is capable of maintaining pancreatic organ homeostasis. As the authors describe in their paper, “A central question in stem cell biology is whether organ homeostasis is maintained in adult organs through undifferentiated stem cells or self-duplication of specialized cell populations. To address this issue in the exocrine pancreas we analyzed the Bmi1-labeled cell lineage of pancreatic acinar cells.” As the authors later conclude, “This study suggests that Bmi1 is a marker for a subpopulation of self-renewing acinar cells, indicating that self-renewal is not an exclusive feature of adult undifferentiated stem cells. This cellular behavior is again reminiscent of behavior normally associated with more classical adult stem cells.” The scientists also discovered that not all of the cells are continually renewing, the reason apparently being that, “Setting aside cells capable of self-renewal until needed retains the advantage of protecting this subpopulation of cells from DNA damage induced during replication.”

While the discovery answers to some degree this “central question in stem cell biology”, as to “whether organ homeostasis is maintained in adult organs through undifferentiated stem cells or self-duplication of specialized populations”, the discovery also highlights to a certain extent the constantly evolving nature of science. In particular, one aspect of science which continually seems to be an ongoing “work in progress” is the very lexicon itself, which is in a constant process of updating and revision, even in the “classical” definitions of accepted terminology. In this particular case, the difference between the classical understanding of an adult stem cell and the more recent definition of acinar cells as a type of “stem cell”, is a matter of pure undifferentiation in the classical case as opposed to some degree of specialized differentiation, with preserved characteristics of self-renewal, in the latter case. Prior to this discovery, acinar cells were merely considered to be pancreatic exocrine cells, known primarily for their ability to release hydrolytic enzymes into the duodenum; now, however, acinar cells may also be considered a type of adult stem cell. All things considered, this is a not-uncommon example of the way in which human definitions that are associated with natural phenomena continually evolve over time, as our understanding of those natural phenomena grows increasingly refined and precise over time – in a somewhat analogous manner to the way in which a mariner who is sailing toward an unknown destination might continually make readjustments to the course, based upon continually changing information about the location of that destination. If or when the destination is ever actually reached, the detailed features of its landscape may prove to be dramatically different from those that were imprecisely seen from a distance.

In the U.K., 49-year-old Irene MacKenzie was displeased with the hollow concavity that was left in her breast following a lumpectomy that she underwent for early-stage breast cancer. Eager to do something to correct the situation, Irene enrolled in a clinical trial and became the first woman in Britain to undergo reconstructive therapy with her own adult stem cells. Since Irene, a total of eleven patients have now been treated with the same procedure, which utilizes adult stem cells derived from the adipose (fat) tissue of each patient. The procedure was performed at the Glasgow Royal Infirmary, under the direction of consulting plastic surgeon Dr. Eva Weiler-Mithoff.

The mother of 3, Irene describes her experience. “When I was diagnosed with breast cancer in my left breast five years ago, I had a lumpectomy, removing the tumor and a healthy margin of tissue. I naturally wanted to preserve as much of my breast as possible. Immediately after surgery my breast didn’t look that bad, but this was because the hole left by the lumpectomy had filled with fluid from the surgery wound. Then I had six weeks of radiotherapy, which dried up a lot of the fluid. The tissue around the area shrank and hardened, pulling the overlying skin deeper into the hollow. I was left with a dense mass, the size of half a plum. Sometimes it caused a painful dragging sensation. I was very self-conscious about it and I went to specialist bra shops for fittings, but I was never comfortable with them.”

The stem cell procedure is relatively simple, as it begins with the extraction of approximately one pint of fat via liposuction from the patient’s stomach. This pint is then divided into two halves, one of which is temporarily set aside while the adult stem cells are extracted from the other half. The stem cells are then combined with the fat from the first half, and the new mixture is injected back into the hollow depression that is commonly left in breasts by lumpectomies. In Irene’s case, after 3 months the stem cell mixture had been assimilated to such an extent that the breast looked and felt like a complete, normal breast once again.

As Irene explains, “Initially, my breast and tummy felt bruised and swollen, but after a few weeks, this went down. Three months later, my stem-cell-treated breast looked and felt like normal breast tissue, even slightly firmer. I had a follow-up appointment at three months and at six months. Mrs. Weiler-Mithoff thought my breast should be topped up slightly because some of the fat had been reabsorbed, so I had more liposuction. Now it looks fantastic and it’s changed my whole outlook.”

Previous procedures have already existed in which liposuctioned fat, without stem cells, was used for reconstruction of the breast, but such procedures have a low graft survival rate of only 30 to 50%, and such techniques are often associated with further problems such as calcification, lump formation and necrosis (death) of the adipose tissue. By contrast, adding adult stem cells to the adipose tissue brings the graft survival up to 80% or higher, since the adult stem cells promote angiogenesis (the growth of new blood vessels) which provides a blood supply to the new tissue, without which the tissue would die.

As Dr. Weiler-Mithoff describes, “We have treated eleven patients so far as part of a European trial into stem cell fat transfer treatment to fill breast defects, and I am very pleased with the results. The patients come to us with mild, but to them, upsetting, contour defects. If you looked at the breast in silhouette, you’d notice a dip. Immediately after a lumpectomy, the area may not look that different. But if it is treated with radiotherapy, it shrinks and pulls in the overlying skin, forming a crater. Until three years ago when some surgeons started filling these craters with fat liposuctioned from one part of the body, there was not much we could do. Now we can inject stem cell-enriched fat into the dip. The big advantage of this over plain liposuctioned fat is that it boosts its chances of survival. Ordinary fat can struggle to get a decent blood supply and it can either die or be absorbed back into the body, or it can calcify and feel like another lump. But if you put stem cells into the breast, they become fat and blood vessels. This stem cell-enriched fat also seems to restore the softness of the breast tissues. It almost uncrumples the skin, undoing some of the radiotherapy damage, and women are reporting that their pain has eased, too, possibly because it makes the skin more supple. Patients have an MRI scan at six and 12 months to check breast volume – if some fat has been reabsorbed a top-up may be required. Patients have another mammogram at the one-year mark.”

Doctors at Leeds General Infirmary, and also at Norfolk and Norwich University Hospitals, are scheduled to begin recruiting more patients for the U.K. trial. Qualifying patients will have had a cancererous tumor that measured 3 centimeters or less in size and which has not spread to the lymph nodes.

Every year more than 31,000 women in the U.K. alone have lumpectomies for early-stage breast cancer. According to Dr. Kefah Mokbel, a breast surgeon at the London Breast Institute at the Princess Grace Hospital, “This is a very exciting advance in breast surgery. The breasts feel more natural because this tissue has the same softness as the rest of the breast.” By contrast, Dr. Mokbel explains, “Implants are a foreign body. They are associated with long-term complications and require replacement. They can also leak and cause scarring.”

The technology was developed by Cytori Therapeutics and is being commercialized in partnership with GE (General Electric) Healthcare. In Japan, doctors at the Seishin Regenerative Medicine Centers in Tokyo and Osaka have already been using this reconstructive procedure for the past 6 years, with an 80% satisfaction rate. Their patients include not only women who have undergone lumpectomies but also women who simply desire cosmetic augmentation.

Meanwhile, however, scientists hope to be able to develop other, better ways to regenerate breast tissue more naturally, more thoroughly, and more efficaciously, although such possibilities have not yet been easily attainable. For years, the mere search for a resident population of human breast stem cells remained without tangible results, although scientists are gradually making progress. According to a report published in January of 2005 by researchers at the University of Manchester in the U.K., breast epithelial stem cells are thought to be the primary targets in the etiology of breast cancers, most of which express cellular estrogen and progesterone receptors and are therefore regulated by these and other hormones in ways that are not yet fully understood. Similarly, in March of 2002, scientists at the University of Copenhagen in Denmark, in collaboration with scientists at the Lawrence Berkeley National Laboratory of the University of California, succeeded in isolating and expanding a stem cell line from endogenous human breast stem cells, i.e., from stem cells that naturally reside within the breast. The scientists focused their study on the terminal duct lobular unit (TDLU), which is a branching mammary structure with luminal epithelial cells on the inside and myoepithelial cells on the outside, from which Dr. Ole William Petersen and his colleagues were able to isolate a luminal epithelial cell population which they referred to as MUC-/ESA+, named after the types of identifying cell surface markers that distinguish the cells. After establishing a MUC-/ESA+ cell line, the researchers were then able to show that these cells can be differentiated into both luminal epithelial cells and myoepithelial cells, and that even a single MUC-/ESA+ cell is capable of generating a TDLU-like structure in vitro, and also in vivo in mice. Additionally, the scientists discovered that these cells also express the keratin K19 protein, as does a subpopulation of luminal epithelial cells in normal breast tissue. Their findings, which were published in the March, 2002 issue of the journal Genes and Development, suggest that the highly elusive human breast stem cell may exist within this subpopulation of the luminal epithelial cell lineage. No doubt a further understanding of breast stem cells would also shed light on the cellular mechanisms at work in transforming otherwise normal cellular tissue into the various types of cancers and malignancies of the breast.

The real question, of course, is not merely how to repair tissue for cosmetic purposes, but how to regenerate the tissue for functional purposes as well. Someday, with regenerative medicine, such a goal may be achievable.

Phrased another way, much more important that mere cosmetics is the possibility of a full regeneration of a breast that was lost to masectomy. After all, to focus exclusively on cosmetic appearance is to lose sight of the fact that breasts, in all mammalian species, are designed to perform a specific biological function which is critical for the survival of that species, namely, to produce a specialized – and in many cases, the only – source of nutrition for newborns. While the repair of an indentation left by a lumpectomy is certainly to be applauded, the ultimate goal is not merely the external appearance of the breast but rather it is the full restoration and regeneration of the entire mammary gland, complete with full physiological function. Some day, regenerative medicine may be able to do exactly that, which would then also result, secondarily, in a restoration of the visual wholeness of the mammary gland, not as an objective in and of itself but as a natural consequence of having restored the entire breast to its original state of physiological wholeness. If scientists can already regenerate fingers with adult stem cells (please see the related news articles on this website, entitled, “Grow Your Own Replacement Parts” dated February 6, 2008, and “Growing Miracles”, dated February 7, 2008, each originally reported by CBS Evening News, and “Growing a New Heart With Adult Stem Cells”, dated March 18, 2009), then it is just a matter of time before the right stem cell is found, such as perhaps an endogenous breast stem cell, which can be utilized after a masectomy to regenerate the entire breast, such that the breast is anatomically and physiologically complete with its full venous, arterial, lymphatic, nerve and milk duct systems as well as papilla, so that the breast would even be capable of lactogenesis and lactation, if necessary, with alveoli, lobules, lactiferous ducts and galactophores that can support colostrum as well as milk production and which are responsive to all the myriad hormones that are involved in pregnancy and lactation. The point is not so much whether or not lactation would ever actually be needed, but rather the point is simply the restoration of natural wholeness. As with any other part of the body, the best way to restore cosmetic appearance is by restoring the internal integrity of physiological tissue and its corresponding function. Restoring complete anatomical and physiological wholeness, with functional viability of the entire mammary gland, would therefore be the best way to restore complete wholeness of cosmetic appearance. Otherwise, just having something that resembles a “breast” in visual appearance but which consists merely of surgically implanted adipose tissue that lacks the precise physiological functionality of a real breast, would be akin to having an artificial prosthesis for a limb, when clearly the real, healthy limb would be more desirable. To continue with the analogy, when a person loses a leg, for example, prosthetics are not necessarily designed to be visually attractive, but, more importantly, they are designed to be able to bear weight and to move in a walking motion and to resemble as closely as possible the functional purpose of a real leg. If all the bones, vessels, veins, tendons, ligaments, musculature and other tissue of the entire, natural leg could be regenerated, that would be even better. Similarly, any woman who has lost an entire breast or even part of a breast would prefer to have the original form and function restored in its natural entirety, not merely in an artificial external form for visual appearance. To be capable of such a medical procedure, however, scientists and physicians would first need to attain control not merely of angiogenic (blood vessel-forming) stem cells, but also of stem cells that form lymphatic tissue, nerve and lactiferous duct systems, among other anatomical and physiological objectives. Then, the correct medical terminology would be “regenerative breast procedure”, rather than “reconstructive breast procedure”.

Although regenerative medicine has not yet advanced to the stage where entire limbs, organs, and glands such as breasts can be regrown, the field is rapidly progressing in that direction.

Researchers have demonstrated significant improvement in heart attack patients following treatment with autologous adult stem cell therapy, according to the results of a clinical trial involving 31 patients.

Prior to receiving the stem cell therapy, all of the patients had been treated with angioplasty and stent placement immediately following a heart attack. Within one week of the heart attack, 16 of the patients received infusions of their own adult stem cells directly into the coronary artery in which a blockage had caused the attack. In accordance with the parameters of the study that were being investigated, the patients received infusions of different quantities of adult stem cells, which consisted either of 5 million, 10 million or of 15 million stem cells. In all cases, the adult stem cells were harvested from each patient’s own bone marrow. Within 3 to 6 months following the treatment, all patients who received the adult stem cell therapy began showing improvement, with the greatest improvement seen in those patients who had received the higher doses of the adult stem cells, all of whom exhibited increased blood flow within the heart as well as the repair and regeneration of cardiac tissue and improved overall cardiac function. Those patients who received lower doses of stem cells also showed improvement although to a lesser extent, and those patients in the control group who received only standard medication and no stem cells at all were found to have the least amount of improvement.

According to Dr. Arshed Quyyumi, professor of medicine at Emory University School of Medicine and a principal investigator in the study, “This is critical information for future study design. The more cells a patient receives, the more beneficial effect we see in the heart. These results show that treatment with a patient’s own bone marrow stem cells has the potential to reduce long-term complications after a heart attack. We are encouraged by these results and are planning to conduct a more extensive study.”

The findings were presented at the American College of Cardiology conference in Orlando, Florida.

Researchers at the Stem Cell Processing Laboratory at the University of Padua in Italy, in collaboration with researchers at INSERM (Institut National de la Sante et de la Recherche Medicale, the national French institute for health and biomedical research) in Paris have isolated c-Kit+ Lin- cells from both human and mouse amniotic fluid for the purposes of investigating the hematopoietic (blood-forming) potential of the cells, which was found to be unusually robust. Also known as “stem cell factor receptor”, the cytokine receptor c-Kit+ is expressed on the surface of hematopoietic stem cells although altered forms have been associated with some types of cancer. Recent independent studies have also demonstrated that Lin- hematopoietic stem cells contain a subpopulation of endothelial precursor cells which are capable of forming blood vessels.

In this particular study, amniotic fluid was collected from pregnant mice between 9.5 and 19.5 days after insemination, from which cells were isolated which were found to have markers similar to those of bone marrow stem and progenitor cells. In vitro, the cells were found to display a multilineage hematopoietic capability, generating erythroid, myeloid and lymphoid cells. In vivo, cells belonging to all 3 hematopoietic lineages were also generated after transplantation into immunocompromised hosts, and the cells were found to exhibit strong self-renewing properties, which is one of the primary traits of stem cells. Similar findings were also obtained from human amniotic fluid that was collected from volunteer human donors between 7 and 35 weeks of pregnancy during routine diagnostic amniocentesis procedures.

According to senior author Marina Cavazzana-Calva, M.D., Ph.D., of INSERM, “Building on observations made by other scientists, our reserach team wondered whether stem cells could be detected in amniotic fluid. We looked at the capacity of these cells to form new blood cells both inside and outside the body, and also compared their characteristics to other well-known sources of stem cells.” As Isabelle Andre-Schmutz, Ph.D., also of INSERM, adds, “The answer was a resounding ‘yes’. The cells we isolated from the amniotic fluid are a new source of stem cells that may potentially be used to treat a variety of human diseases.”

Amniotic fluid, also known as liquor amnii, is the liquid contained within the amnion, which is the membranous sac that surrounds an embryo, the primary purpose of which is protection during development. Amniotic fluid is known to contain a variety of substances, especially after the tenth week of human embryonic development at which time the fluid is rich in lipids, phospholipids, proteins, carbohydrates, urea and electrolytes, among other substances. Amniocentesis, in which fetal cells within the amniotic fluid are analyzed and screened for genetic defects in the developing fetus, is a routinely performed procedure precisely because such fetal cells are readily detectable within the fluid during gestation.

Previous research conducted by scientists at Wake Forest University and Harvard University in 2007 independently confirmed that amniotic fluid contains non-embryonic stem cells which differentiate into a variety of cell types including tissues of the liver, bone and brain. That same year Swiss researcher Dr. Simon Hoerstrup also demonstrated the ability of stem cells from amniotic fluid to differentiate into cardiac cells.

However, given the growing evidence that not only embryonic but also fetal stem cells can cause tumors, and especially in light of the recent medical publication that reported the condition of the Israeli boy who developed a life-threatening tumor that genetically matched the fetal stem cells that he had received as a therapy, it is especially important for scientists and physicians to be extra cautious about knowing whether or not even stem cells derived from amniotic fluid will cause tumors, since no “therapy” should generate more physical problems than those which it is meant to treat. As we have often stated on this website, ethics and politics aside, there are enough scientific hurdles which still need to be overcome before any embryonic, fetal, or pluripotent stem cell of any type (including the iPS cells, which are not stem cells but nevertheless exhibit pluripotency) can be safely and effectively used as a clinical therapy. Nevertheless, the discovery of stem cells within amniotic fluid that have now been shown to differentiate into a wide variety of tissue types offers yet another example by which stem cells can be obtained without the need for embryos. (Please see the related news article on this website, entitled, “Fetal Stem Cell Therapy Could Prove Fatal”, dated February 17, 2009, as originally reported by PLoS Medicine).

The recent findings on the hematopoietic potential of amniotic cells were published in the journal Blood, a publication of the American Society of Hematology, the world’s largest professional society that studies the causes and treatment of blood disorders.

In the past, iPS (induced pluripotent stem) cells were obtained by reprogramming dermal fibroblasts obtained by skin biopsy, first in mice and later in humans. The reprogramming involved a de-differentiation process by which ordinary somatic (non-stem cell) cells were induced to revert to a more primitive state in which they exhibit a pluripotency that resembles that of embryonic stem cells. Now, for the first time, scientists have derived iPS cells from reprogrammed CD34+ cells that are mobilized from human peripheral blood.

In a study led by Dr. Yuin-Han Loh of Children’s Hospital in Boston, and in collaboration with scientists at the Dana-Farber Cancer Institute, the Brigham and Women’s Hospital, the Howard Hughes Medical Institute and the Harvard Stem Cell Institute, researchers have developed a new application of the same laboratory methods that are by now well known among stem cell scientists for deriving iPS cells. Using retroviral transduction of Oct4/SOX2/KLF4 (transcription factors involved in cellular self-renewal and differentiation) and c-Myc (a gene involved in protein-coding, a mutated version of which is known to be oncogenic, or in other words, it can cause cancer; in fact the entire Myc family of genes are known as proto-oncogenes and are implicated in some types of cancer when mutated or overexpressed), the researchers succeeded in generating a blood-derived iPS cell which they describe as being “indistinguishable from human embryonic stem cells (hESCs) with respect to morphology, expression of surface antigens and pluripotency-associated transcription factors”, among other characteristics. In fact, the newly formed iPS cells were also found to resemble hESCs in DNA methylation status at pluripotent cell-specific genes, and also, the authors point out, in the capacity of these newly formed iPS cells “to differentiate in vitro and in teratomas”.

Indeed, as with hESCs and all other types of pluripotent cells, any and every type of iPS cell must be able to form teratomas (a specific type of tumor which contains cells from all 3 germ layers) since this is part of the formal scientific definition of pluripotency, and if a cell cannot form the type of tumor known as a teratoma then it is not pluripotent. By contrast, since adult stem cells are multipotent at best, not pluripotent, adult stem cells do not carry the risk of teratoma formation. CD34+ cells are already recognized as a type of “adult” stem cell and as such they do not exhibit pluripotency and therefore cannot form teratomas. This most recent study by Dr. Loh and his colleagues, however, has shown that any type of cell will be able to form dangerous teratomas once it has been reprogrammed to a more primitive, pluripotent state.

Although the lack of pluripotency was previously seen as a disadvantage of adult stem cells, increasingly it is recognized as a distinct advantage since it allows for more certainty and control of the differentiation of the adult stem cells into only the desired type of tissue, without the danger of tumor formation which is so characteristic of embryonic and fetal stem cells, and even without the simpler danger of the wrong type of tissue formation (such as the accidental formation of bone within cardiac or neurological tissue, etc.). Nevertheless, the lure of pluripotency remains irresistible to many scientists, and iPS cells are still highly coveted, especially since they can be created without having to destroy an embryo, even though iPS cells resemble embryonic stem cells in their pluripotency, which thereby circumvents the ethical debates that are inextricably entangled in embryonic stem cell research. However, as pluripotent cells, iPS cells still pose the same medical risks as do embryonic stem cells, only one of which is the danger of teratoma formation, and for this reason scientists agree that at least another decade is needed before iPS cells can become available as clinical therapies at your local neighborhood doctor’s office. Meanwhile, adult stem cells are already being used in clinics around the world as therapies for a wide variety of illnesses and injuries, since, as already explained, adult stem cells are multipotent, not pluripotent, and as such they cannot form teratomas nor do adult stem cells carry any of the other medical risks that are associated with embryonic and iPS cells (such as genetic mutation and biological contamination in the case of embryonic stem cells, and cellular reprogramming agents that include cancer-causing genes delivered by dangerous retroviruses in the case of iPS cells, among other problems). In their natural state, CD34+ cells are already being used in clinics around the world to treat a wide variety of illnesses and injuries; in their reprogrammed, artificially induced pluripotent state, however, they behave just like embryonic stem cells and hence are unusable as a clinical therapy, at least until scientists figure out how to eliminate the associated dangers such as teratoma formation, among others, which even the most ambitious of stem cell scientists concedes will require another decade of research.

As one of the many “cluster of differentiation” (CD) molecules, CD34 is a glycoprotein present on the surface of some cells within the human body, and it is merely one of the many CD cell surface markers that have been identified. Cells expressing the CD34 molecule (CD34+ cells, according to the nomenclature) have been found in a number of regions throughout the human body including the dermis, but are most abundant in bone marrow and umbilical cord blood where the CD34+ cells exhibit strong hematopoietic (blood-forming) capabilities. Perhaps most importantly, CD34+ cells are also present in peripheral blood as endothelial progenitor cells (cells originating in the bone marrow that circulate throughout the blood and are capable of differentiating into the cells that line blood vessels), and in this capacity they have been found to play a central role in cardiovascular health, especially in recovery following myocardial infarction. It is believed that any event which causes acute damage to blood vessels such as a myocardial infarction will trigger the automatic mobilization of endothelial progenitor cells and their migration out of the bone marrow into the blood stream where they can repair damaged blood vessels. Heart attack patients who have been found to have high levels of circulating endothelial progenitor cells in their blood stream exhibit greater and faster improvement than do patients with lower levels of the cells circulating in their bloodstream, and a number of studies have proposed the dedicated use of concentrated amounts of endothelial progenitor cells in a variety of cardiovascular therapies. Most notably, surgeons at Harvard Medical School described in a 2007 report a method of using the cells to construct organic pediatric heart valves that would, unlike other heart valves, be capable of growing with the child.

In fact, CD34+ cells have already proven to be so useful as a type of “adult” stem cell, that one wonders why anyone would want to tamper with them and try to change anything about the characteristics of these extremely versatile cells. In their natural state, not only are CD34+ cells highly regenerative but they have also been shown to be safe, from numerous clinical therapies that have been conducted over many years around the world and reported in the medical literature. Nevertheless, when reprogrammed to a more primitive, pluripotent state, even CD34+ cells will form teratomas, just as embryonic and all other iPS cells must, by definition, do. One also wonders why Dr. Loh and his colleagues didn’t try to derive iPS cells from a more ordinary type of blood cell, such as from a white blood cell (leukocyte), for example, which is also known to differentiate from hematopoietic cells within the bone marrow but which is much more plentiful within the blood than are CD34+ cells.

Since the derivation of peripheral blood involves a much easier and less invasive procedure than does the harvesting of a skin cell, proponents of iPS cells point out that the generation of iPS cells from reprogrammed human blood cells may now expedite research into patient-specific stem cells – even though patient-specific stem cell research is already being conducted with adult stem cells. Be that as it may, and even though many scientific hurdles still remain to be overcome before such iPS cells may be available as clinical therapies, nevertheless this is merely one more demonstration of the fact that pluripotent cells may be obtained through a variety of methods, without the need for embryos.

One can only wonder how much longer it will be before iPS cells will be derivable from any type of ordinary somatic cell that is obtainable from any type of tissue from anywhere throughout the adult human body.