The U.S. Patent and Trade Office has awarded patent # 7,517,686 to scientists at the Blasticon Biotechnologische Forschung GmbH in Germany for their invention of a method by which dedifferentiated, programmable stem cells of monocytic origin are created. The invention also describes pharmaceutical applications and methods for differentiating the stem cells into target cells and tissue.

A type of white blood cell with distinct immunological properties, monocytes are conveniently obtained from peripheral blood which is easily drawn from a simple intravenous blood collection. Originally produced in the bone marrow from hematopoietic precursor cells known as monoblasts, monocytes play a central role in immune and inflammatory responses and are routinely measured for diagnostic purposes in a complete blood count.

The patent description includes methods for isolating monocytes from human blood, culturing the monocytes in a medium containing the cytokine and cellular growth factor M-CSF (macrophage colony stimulating factor) as well as IL-3 (interleukin-3), from which the dedifferentiated programmable stem cells are found to express the CD14, CD90 and CD123 antigens. As the authors explain in the “background” of their invention, “The use of embryonic stem cells has been the subject of extensive public discussion, especially in Germany, and is regarded as extremely problematical. Besides the ethical and legal problems connected with embryonic stem cells, the therapeutic use of such cells also comes up against difficulties. By nature, embryonic stem cells are obtained from donor organisms, which are heterologous vis-a-vis the potential recipients of differentiated cells or tissue (hereafter referred to as somatic target cells or target tissue) developed from these cells. It is therefore to be expected that such target cells will trigger an immediate immunological response in the potential recipients in the form of rejection.” By contrast, the derivation of pluripotent stem cells from autologous monocytes that are collected from ordinary adult peripheral blood circumvents such difficulties.

As the authors further explain, “the foreseeable development of the age and disease profile of the population in the western world is decisive, leading to the expectation of a drastic turning point in the next 10 years in the health and care sector of the western European population, including the USA and Canada. In the Federal Republic of Germany alone, the demographic development suggests a 21% growth in population in the 45 to 64 year-old age group by 2015, and a 26% growth in the over-65 age group. This is bound to result in a change in patient structure and in the spectrum of diseases requiring treatment. Predictably, diseases of the cardio-circulatory system (high blood pressure, myocardial infarction), vascular diseases due to arteriosclerosis, and metabolic diseases such an diabetes mellitus, diseases of liver metabolism, kidney diseases as well as diseases of the skeletal system caused by age-related degeneration, and degenerative diseases of the cerebrum caused by neuronal and glial cell losses will increase and require innovative treatment concepts. These facts explain the immense national and international research and development efforts by the specialists involved, to obtain stem cells which can be programmed into differentiated cells typical of tissue (liver, bone, cartilage, muscle, skin etc.). The problem underlying the invention therefore resides in making available adult stem cells, the generation of which gives rise to no ethical and/or legal problems, which are rapidly available for the planned therapeutic use in the quantities required for this, and at justifiable production costs, and which, when used as ‘cellular therapeutics’ give rise to no side effects – or none worth mentioning – in terms of cellular rejection and induction of tumors, particularly malignant tumors, in the patient in question.”

Within the claims of their invention the scientists propose methods for treating a number of diseases which include cirrhosis of the liver, pancreatic insufficiency, acute and chronic kidney failure, hormonal underfunctioning, cardiac infarction, pulmonary embolism, stroke and skin damage. Additionally, implantable prostheses for various anatomical structures such as cardiac valves and vessel prostheses as well as bone and joint prostheses are also described. Such claims are possible since the invention describes the dedifferentiation and redifferentiation of the monocytes into a variety of target cell and tissue types which include neuronal precursor cells, neurons and glial cells, endothelial cells, adipocytes (fat cells), hepatocytes (liver cells), keratinocytes (skin cells), and insulin-producing (pancreatic beta islet) cells. The authors further describe the coexpression of albumin and the monocyte-specific antigen CD14 in the hepatocytes, as well as the in vivo use of the cells in an animal model.

As the authors explain, “The generation of the stem cells according to the invention is completely harmless to the patient and – in the case of autologous use – comparable to own blood donation. The quantity of stem cells required for the usual therapy options can be made available cost-effectively within 10 to 14 days after the blood is taken. In addition the cell product provided for the therapy, in the case of autologous use, does not give rise to any immunological problem in terms of cell rejection, as cells and recipient are preferably genetically identical.”

The claims of the invention also include an absence of the threat of cancerous malignancy, since, as the authors describe, “The stem cells according to the invention have also proved to be risk-free in animal experimentation and in culture with regard to giving rise to malignancy, a result which is only to be expected due to the cell of monocytic origin, from which the stem cells according to the invention derive.”

Unlike the iPS (induced pluripotent stem) cells that are often in the news and which carry a number of risks not only because of their ability to form teratomas (tumors) but also because of the oncogenes (cancer causing genes) with which they are produced, these new stem cells of monocytic origin are created without oncogenes through a very different dedifferentiation process. The authors describe genetic transfection of the cells with the FAH (fumarylacetoacetate hydrolase) gene, and transfection with “multidrug resistant genes” such that “extended radical chemotherapy can be made possible in the case of malignant diseases by corresponding hematopoietic reconstitution, or radiation resistance can be produced.”

Even though monocytes are ordinarily collected and separated from whole blood, they could also be alternatively obtained directly from organs, if necessary, such as in the case of contraindicating blood conditions such as anemia or leukemia, for example.

Although the patent was awarded today, the patent application was originally filed on November 21st of 2005.

Led by Dr. Patrick Lee of the Department of Microbiology and Infectious Diseases at the University of Calgary, scientists have discovered that the commonly occurring reovirus can selectively target and destroy the cancerous stem cells that cause breast cancer. Additionally, the reovirus also exhibits other beneficial cellular and molecular action by stimulating the body’s immune system and natural anti-cancer defense mechanisms.

It was over a decade ago, in 1998, when Dr. Lee originally announced his discovery that the reovirus (an acronym for Respiratory Enteric Orphan virus) can kill cancer cells. Now, the discovery has been extended specifically to breast cancer stem cells, which are the “master cells” gone awry and which consequently generate cancer cells in the breast.

As Dr. Lee explains, "You can kill all the regular cancer cells in a tumor, but as long as there are cancer stem cells present, disease will recur." Indeed, it has taken the medical profession awhile to appreciate the full significance of cancer stem cells and the importance of eliminating these stem cells in any clinical cancer treatment. Cancer stem cells are difficult to kill, however, and are often highly resistant to standard chemotherapy and radiation treatments, which accounts for the low success rates of chemotherapy and radiation. As Dr. Lee further explains "Cancer stem cells are essentially mother cells. They continuously produce new cancer cells, aggressively forming tumors even when there are only a few of them. Cancer stem cells just keep churning out new cancer cells. No matter how many cancer cells you kill, you can’t stop the cancer until you kill the stem cells." Even if the cancer stem cells themselves remain in very small numbers, they can still produce new tumors, in large numbers. Without eliminating the cancer stem cells in their entirety, the cancer that is produced by the stem cells can never be fully eliminated. The only way to "cure" any particular type of cancer, therefore, in the absolute sense of the word, is to get to the root of the problem and eliminate the cancer stem cells.

Now, in an effort to do exactly that, scientists are looking at ways of utilizing the reovirus as a virus-based anti-cancer therapy, which is currently being tested in 10 clinical trials, 4 in the U.K., and 6 in the U.S., under the name “Reolysin”, which is marketed by the Canadian company Oncolytics Biotech. Although the current issue of the journal Molecular Therapy describes a study in which the reovirus is utilized for the specific treatment of breast cancer, the study complements and corroborates a number of other clinical and preclinical studies in which the reovirus is also utilized to treat other forms of cancer as well.

The mechanism-of-action of the reovirus is particularly advantageous as a cancer therapy, since the reovirus has been found to preferentially replicate in Ras-activated cancer cells, thereby causing virus-mediated cell death. Additionally, scientists have discovered that the tumor antigens generated by viral oncolysis (the destruction of tumor cells) may “educate” the immune system to recognize and kill similar tumor cells in the future. Based upon principles such as these, the proprietary anti-cancer product Reolysin has been formulated to replicate specifically in tumor cells that bear an activated Ras pathway, and which are therefore also deficient in their ability to activate a natural anti-viral response as mediated by PKR (protein kinase R) activity, which is present in normal cells but absent in tumor cells with activated Ras pathways, since normal cells do not possess activated Ras pathways. As the tumor cells die, the progeny viral particles in turn spread to neighboring cells, a process which in turn triggers the continuous cycle of infection, replication and cell death – a cellular cycle that repeats itself until there are no more tumor cells remaining which bear the activated Ras pathway.

The activated Ras pathway is one of the most common genetic defects that are known to predispose an individual to developing cancer, and it is believed that the activation of mutations in Ras, as well as in upstream elements of Ras, may be implicated in more than two-thirds of all human cancers. Scientists therefore hope that Reolysin may represent a novel treatment not only for Ras-activated tumor cells but also for other types of cellular proliferative disorders.

Reovirus is commonly known to inhabit the human respiratory and bowel systems, being naturally found in sewage and water supplies, but it is nonpathogenic. Its anti-cancer properties were first established after the reovirus was found to replicate so easily within Ras-activated cancer cell lines. According to Dr. Lee, “The cancer cell environment lets the virus uncoat and start reproducing more quickly than it can in normal cells. The rapidly growing mass of virus particles ruptures the infected cancer cell, releasing virus particles to infect other cancer cells in the body. So theoretically it can even kill cancers that have metastasized.” Dr. Lee adds, "We suspected that reovirus might be effective against cancer stem cells, because we have shown time and again how well it destroys regular cancer cells."

Unlike most cancer studies, which use cancer cell lines that have been developed exclusively for laboratory use, Dr. Lee’s study utilized fresh breast cancer tissue that was derived from a live patient. As Dr. Lee explains, "Refining this two-pronged approach to killing cancer is our next step. We are taking advantage of the natural characteristics of reovirus and the immune system itself to create a powerful virus-based anti-cancer therapy."

Additionally, Oncolytics Biotech has developed a clinical program which includes human trials that use Reolysin by itself and also in combination with radiation and chemotherapy. Headquartered in Calgary, Alberta, Oncolytics Biotech was founded in 1998 for the specific purpose of developing pharmaceutical cancer therapies that are based upon the oncolytic properties of the reovirus. Thus far, Oncolytics Biotech has concluded nine human Phase I/II clinical trials in the U.K. and the U.S. which have yielded positive interim data for lung, liver and nodal metastatic disease. Additionally, Reolysin is in Phase II/III clinical trials for patients with refractory head and neck cancers, and Oncolytics is currently in a collaborative agreement with the U.S. National Cancer Institute for the design of multiple clinical trials. Independent preclinical studies have also demonstrated that the reovirus can destroy cancers of the brain, ovary, prostate, breast and colon, in addition to melanoma and lymphoma.

Another important variable is the transcription factor p53 which normally plays a role in tumor suppression. According to Dr. Lee, “Learning how p53 works and why it loses its protective function in cancer could well lead to a cure.”

In the United States, cancer is responsible for one out of every four deaths, ranking second only to cardiovascular disease in prevalence. Approximately 1.4 million people in the U.S. were diagnosed with cancer in 2008 alone, more than half of whom are expected to die from the disease. The probability of developing cancer at some point in life is approximately 50% (or one out of every two people) for the average U.S. male, and approximately 33% (or one out of every 3 people) for the average U.S. female. In 2007 the U.S. National Institutes of Health estimated that the overall annual cost for all types of cancers combined in the United States was $219.2 billion, of which $89 billion was directly attributable to medical expenses while the remaining $130.2 was attributable to lost productivity

Dr. Patrick Lee is a founding member of the Beatrice Hunter Cancer Research Institute at the Dalhousie University Medical School in Halifax, Nova Scotia.

Molecular Therapy is a journal of the American Society of Gene Therapy.

Researchers in China have demonstrated in female mice that ovaries produce new eggs throughout adulthood, which can then develop into offspring. The discovery overturns a previous theory which was applied not just to humans but to all mammals in general and which held that female mammals are born with a finite number of oocytes (the female gametocyte that develops into ova, or eggs), a number which cannot increase throughout life. Now, however, there is evidence to indicate that the number of oocytes can, and does, increase throughout the lifetime of the female. Apparently, it would seem as though the previous theory did not take into account the concept of a stem cell.

In a study led by Dr. Ji Wu, a professor at Shanghai Jiao Tong University, the researchers isolated female germline stem cells (FGSCs) from adult mice and also from five-day-old infant mice. Even after being cultured several times, regardless of age, all the FGSCs were still found to proliferate. Most interestingly, the adult FGSCs continued to produce new oocytes and thereby restored fertility when transplanted into the ovaries of female mice who were previously infertile, and who subsequently gave birth to normal mice.

According to Dr. Paul Sandberg, professor of neurosurgery and director of the University of South Florida Center for Aging and Brain Repair in Tampa, “These stem cells are continuous. They were still around through life and actually transformed to make oocytes. Then they were transplanted into infertile females and produced offspring.”

Scientists now hope that applications of this discovery could be extended to the development of a new stem cell therapy for infertility in human females. Some researchers are cautious of such high hopes, however, such as Dr. George Attia, associate professor of reproductive endocrinology and infertility at the University of Miami Miller School of Medicine, who states, “If it would ever come to fruition in humans, I really don’t know. It’s far, far out there.” As Dr. Darwin J. Prockop, director of the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine, adds, “There are too many steps, too many things could go wrong.”

Nevertheless, the idea that female mammalian babies are born with all the ova that they will ever have in their entire lives – a theory which never made much sense to a lot of people – has now been disproven. As with spermatocytes, the male gametocytes from which spermatozoa develop, there is now evidence to indicate that oocytes in females are also replenished throughout life.

The biotech company Cryo-Cell International announced in its earnings report today that its net income for the first quarter of the 2009 fiscal year was $536,000, a significant increase from its net loss of $247,000 in the first quarter of the 2008 fiscal year. Total revenue as of February 28 was reported at $3.9 million for the year, with approximately $5.7 million in available cash, cash equivalents, marketable securities and other investments. By the end of the quarter, the company no longer had any long-term debt.

According to Mercedes Walton, chairwoman and CEO of Cryo-Cell, the company was able to reduce administrative, marketing and sales expenses over the previous year, while prospective clients increased 94%. Licensee income for the first quarter totalled approximately $338,000, compared to approximately $183,000 for the first quarter in 2008. As Ms. Walton explains, “We are clearly encouraged by Cryo-Cell’s performance in the first quarter of fiscal 2009, which represents the company’s second consecutive quarter of recurring profitability. Despite the weakness in the U.S. economy and its impact on discretionary consumer spending, Cryo-Cell is pleased to deliver first quarter 2009 earnings of $536,000 and gross margins of 71%. Cryo-Cell continues to make substantial progress both strategically and operationally. Our momentum is strong, and we anticipate that shareholder value will increasingly reflect the company’s solid performance and growing enterprise value, potentially driven in part by a loyal and emerging base of over 175,000 clients worldwid, Cryo-Cell’s expansive IP portfolio and an independently funded R&D pipeline, in addition to the company’s progressive global leadership in stem cell innovation.”

Cryo-Cell is one of the world’s largest cord blood banks, having collected over 175,000 cord blood specimens from newborns around the world since its founding in 1992. Headquartered in Florida, Cryo-Cell specializes in both the processing and cryogenic storage of adult stem cells from umbilical cord blood. Given the fact that prospective clients have increased 94% since last year, it would seem as though an increasing number of people are realizing the benefits of umbilical cord blood banking.

At his home on the New Jersey shore, Higgins was suffering from age-related arthritis. A 9-year-old Golden Retriever, he then underwent a veterinary procedure at the Toms River Animal Hospital in which his own adult canine stem cells were used as his therapy. Now, Higgins is once again pain-free and back to his regular self.

According to veterinarian Dr. Michele Reimer, “In animals, it’s definitely an up-and-coming field and it’s going to open up a lot of treatment approaches for us. It opens another avenue of treatment for the dog. If we can help a dog not need medications long-term, that’s a huge benefit.”

The stem cells were harvested from the adipose (fat) tissue of the dog’s belly on Monday, shipped to the biotech company Vet-Stem in San Diego, and returned to the clinic in New Jersey by Wednesday, at which time the cells were injected directly into the dog’s arthritic joints.

According to Julie Ryan Johnson, vice president of sales and marketing for Vet-Stem, “The procedure has been shown to help with the range of motion, helps get muscle structure back, helps the dog feel better and improves their quality of life, and they often interact with the family more. It’s a very interesting way to use stem cells because the stem cells actually come from the animal’s own fat, so it’s not controversial.”

As previously reported a number of times on this website, the company Vet-Stem continues to see consistently high success rates in both canine and equine clinical trials, with an 80% efficacy rate and a 100% safety rate in the animals that are treated with Vet-Stem’s autologous adult stem cell procedure. In other words, 80% of the animals treated are found to experience improvement in their condition with a reduction and often a full elimination of the need for medication, while adverse side effects have not been reported in any of the treated animals.

Vet-Stem uses exclusively adult stem cells, derived from each animal’s own tissue. Since the cells are autologous (in which the donor and recipient are the same animal), there is no risk of immune rejection. More specifically, the stem cells that are harvested in Vet-Stem’s procedure are mesenchymal stem cells, which are highly potent adult stem cells that are also found in bone marrow and umbilical cord blood. Numerous scientific and clinical studies have been published in the peer-reviewed medical literature detailing the regenerative properties of mesenchymal stem cells. No embryonic stem cells are ever used in Vet-Stem’s therapies, since embryonic stem cells are highly problematic in the laboratory, whether they are of human or non-human origin. Among other problems, the risk of teratoma (tumor) formation disqualifies embryonic stem cells for use as a clinical therapy, even in animals. Adult stem cells, however, do not pose such risks and are therefore rapidly accumulating a consistent history of successful clinical treatments in veterinary, as well as in human, medicine.

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.