It is widely accepted that stem cells are involved in tissue regeneration. It is also widely accepted that (in most organs) stem cells are vanishingly rare. So: if there doesn’t happen to be a stem cell adjacent to a site of damage, how can stem cells be involved in the process of tissue repair?
One possible answer: There might be more stem cells than we think, because we’ve been missing them for some reason. This possibility (”both”) is strongly supported by the recent findings of Zuba-Surma et al., who have discovered a population of tiny pluripotent cells (termed, appropriately, very small embryonic-like, or VSELs) scattered throughout the body.
Very small embryonic-like stem cells in adult tissues—Potential implications for aging
Recently our group identified in murine bone marrow (BM) and human cord blood (CB), a rare population of very small embryonic-like (VSEL) stem cells. We hypothesize that these cells are deposited during embryonic development in BM as a mobile pool of circulating pluripotent stem cells (PSC) that play a pivotal role in postnatal tissue turnover both of non-hematopoietic and hematopoietic tissues.(cont.)
During in vitro co-cultures with murine myoblastic C2C12 cells, VSELs form spheres that contain primitive stem cells. Cells isolated from these spheres may give rise to cells from all three germ layers when plated in tissue specific media. The number of murine VSELs and their ability to form spheres decreases with the age and is reduced in short-living murine strains. Thus, developmental deposition of VSELs in adult tissues may potentially play an underappreciated role in regulating the rejuvenation of senescent organs. We envision that the regenerative potential of these cells could be harnessed to decelerate aging processes.
Note that both VSEL number and potency diminish with age, consistent with the decrease in proliferative and regenerative capacity that we see in older animals. (And recall that diminishing stem cell potency is just one side of the story: over the course of aging, tissue microenvironments themselves grow more hostile to stem cell growth and function).
The small size of the VSELs, along with their dispersal throughout the body, might explain why they’d been missed up until now. It makes sense that cells devoted to long-term storage of regenerative potential would be very little: other than surviving and maintaining the ability to respond to proliferative signals, they wouldn’t really have much in the way of functional requirements, and wouldn’t need much more than a nucleus, a membrane, and extremely vigilant signal-transduction pathways — the latter ready to awaken the dormant cell when it’s time to turn into a proper stem cell, divide, and differentiate. In a sense, then, these VSELs are not so much progenitors as “progenitor progenitors”, the of regenerative capacity lying silent until they are needed.
(Extending this admitted over-interpretation — small size, after all, does not mean low metabolism, but I’m reasoning by analogy to spores and other very small totipotent cellular forms — another advantage of keeping stem cells metabolically inactive is that they would be less likely to suffer mutations or other damage that could convert them into cancer stem cells.)
Required skepticism: VSELs are both brand new and (so far as I can tell) idiosyncratic to a single group’s work. Before we get too worked up about this, I’d like to see the work reproduced by other labs and in other systems. Hopefully that sort of confirmation is already underway.
Stem cells cultured by researchers on a simple contact lens miraculously restored sight to sufferers of blinding corneal disease.
The simple and inexpensive procedure, considered a breakthrough, requires a minimal hospital stay and significantly improves vision within weeks.
University of New South Wales (UNSW) researchers from its School of Medical Sciences harvested stem cells from patients’ own eyes to rehabilitate the damaged cornea.
The stem cells were cultured on a common therapeutic contact lens which was then placed onto the damaged cornea for 10 days, during which the cells were able to re-colonise the damaged eye surface.
While the novel procedure was used to rehabilitate damaged corneas, the researchers say it offers hope to people with a range of blinding eye conditions and could have applications in other organs.
The trial was conducted on three patients; two with extensive corneal damage resulting from multiple surgeries to remove ocular melanomas (a cancer of the eye), and one with the genetic eye condition aniridia.
Other causes of cornea damage can include chemical or thermal burns, bacterial infection and chemotherapy.
“The procedure is totally simple and cheap,” said study author, UNSW’s Nick Di Girolamo. “Unlike other techniques, it requires no foreign human or animal products, only the patient’s own serum, and is completely non-invasive.
“There’s no suturing, there is no major operation: all that’s involved is harvesting a minute amount — less than a millimetre — of tissue from the ocular surface,” Mr. Di Girolamo said.
“If you’re going to be treating these sorts of diseases in third world countries all you need is the surgeon and a lab for cell culture. You don’t need any fancy equipment.”
Because the procedure uses the patient’s own stem cells harvested from their eye, it is ideal for sufferers of unilateral eye disease. However, it also works in patients who have had both eyes damaged, Mr. Di Girolamo said, according to an UNSW release.
“If we can do this procedure in the eye, I don’t see why it wouldn’t work in other major organs such as the skin, which behaves in a very similar way to the cornea,” Mr. Di Girolamo said.
Genetically engineered adult stem cells, armed with a cancer-killing protein, have proven successful at targeting several types of tumors while sparing healthy cells, new research has found.
Stem cells carrying TNF-related apoptosis-inducing ligand (TRAIL) destroyed lung, squamous, breast and cervical cancer cells in laboratory cultures, according to British researchers. When tried on mice, the specialized cells shrunk subcutaneous breast tumors by about 80 percent, and when injected intravenously, they helped destroy about 38 percent of metastasized lung tumors in rodents.
The study results combined findings from two previous areas of research: one that found that mesenchymal stem cells (MSCs), which come from bone marrow, can work as messengers to tumors cells, and another that found TRAIL effective at killing cancer while sparing healthy cells.
“This is the first study to demonstrate a significant reduction in tumor burden with inducible TRAIL-expressing MSCs in a well-controlled and specifically directed therapy,” the authors, Dr. Michael Loebinger and Dr. Sam M. Janes of the Centre for Respiratory Research at the University College London, noted in a news release from the American Thoracic Society. The findings were to be presented Tuesday in San Diego at the society’s International Conference.
Despite the success, the authors said it could be at least two years before these specialized stem cells are tried on people. Loebinger noted, for example, that while the MSCs seem to be naturally drawn to the cancer cells, the reasons for this are not fully understood.
More information
The U.S. National Institutes of Health has more about stem cells.
LifeCell International India’s first & the largest stem cell banking service provider, which has also pioneered in stem cell research and technology, today announced its association with Harvest Technologies, a world leader in developing technologies that accelerate natural healing, to bring-in a next generation technology Bone Marrow Aspirate Concentrate (BMAC) system in India. BMAC is a USFDA and CE approved biological technology that accelerates the body’s natural healing capacity, thereby improving surgical outcomes.
Existing methods to produce a stem cell concentrate therapy are time consuming, labour intensive, and require complex logistical considerations. The BMAC System helps in safe and rapid preparation of cell concentrate from bone marrow. The process takes only about 15 minutes and can be conducted in the point of care setting.
The system is currently being used clinically in many developed countries like US and Europe for various medical disciplines. These applications range from fractures, non-unions, osteonecrosis, cartilage repair applications and critical limb ischemia (CLI). The system will soon be applied for cardio vascular regeneration.
LifeCell has implemented this technology for an ongoing Indian CLI study which is being led by Dr. K. S. Vijayragavan at Department of Vascular Surgery, SRMC. As per the data available on the interim study conduted on 30 patients after a 12 week followup major amputations were seen only in 4 patients and 6 of them went for minor amputation. The patients’s also reported significant reduction in their pain perception and considerable improvement in quality of life. The study also emphasised the fact that the BMAC process is safe and the Intra-arterial infusion does not cause any adverse reaction.
Talking on the association with Harvest Technologies, Mr. Mayur Abhaya, Executive Director, LifeCell International says, “We are excited to partner with Harvest Technologies to bring-in international standards to India. LifeCell International is today India’s only comprehensive stem cells solutions provider as we offer a complete spectrum of services and with this association we intend to accelerate the availability of advanced stem cell therapy in India.
According to Scott Shea, Managing Director, Harvests Technologies GmbH, “The Autologous regenerative cells from bone marrow offer profound potential for therapies. Harvest has conducted about 30,000 clinical procedures for various applications, the highest number of procedures in the world, using the BMAC System. Our novel technology now makes it possible to harvest the regenerative cells safely and rapidly in order to develop new therapies for heretofore incurable diseases.”
“We are delighted to be associated with LifeCell, an undisputed market leader in stem cell technology space and extend our services in India. LifeCell has a well established network with hospitals and clinical institutions across India and we would leverage their strength to rapidly deploy our service across the country and provide HOPE in addressing unmet medical challenges by offering cellular therapeutic options.”
Commenting on the interim report presented on the studies conducted for CLI in India using the BMAC technology, Mr. Mayur added, “Through our clinical research, we have identified that the transplantation of autologous Bone Marrow Aspirate Concentrate (BMAC) into critically ischemic leg can increase blood flow and support in healing the wounds quickly. It also helps in reducing pain and avoiding leg amputation of otherwise incurable patients. This is also validated by the outcome of the CLI study which showed that 86.6% of patients could avoid amputation.”
About LifeCell International Pvt. Ltd: LifeCell is India’s first & largest umbilical cord blood stem cell bank to bring the revolutionary concept of banking a baby’s umbilical cord blood stem to the country. LifeCell facilitates the cryogenic preservation of stem cells in technological collaboration with Cryo-Cell International Inc, USA – the world’s largest and oldest stem cell bank with more than 16 years of expertise in stem cell banking.
LifeCell in the past 4 years has positioned itself as leaders in the Industry and was recently accredited by AABB (American Association of Blood Banks) for adopting their international standards and today LifeCell is the “First & only AABB Accredited Stem Cell Bank in India” and recognized by DSIR, Govt. of India for R&D. Today LifeCell has over 20,000 members who have preserved their baby’s cord blood stem cells and has over 40 centers across India and abroad. The company will soon be launching another revolutionary service of Menstrual Blood Stem Cell Banking for every woman to preserve her stem cells and potentially secure her future from life-threatening diseases. With addition of this service LifeCell will become the first & only comprehensive stem cells solutions provider in the world to offer a complete spectrum of services in stem cells through multi-service banking, R&D, Clinical Trials and Stem Cell Therapy.
The 2009 World Stem Cell Summit will focus on the science, business, policy, law and ethics of all stem cell types including human embryonic stem cells, adult stem cells and induced pluripotent stem cells.
To maximize the potential of stem cell research, the 2009 World Stem Cell Summit program is designed to cover the field’s most pressing topics including: progressive research strategies, translational and preclinical findings, cross disciplinary initiatives, drug discovery, funding opportunities (federal, public and private), commercialization plans, technology transfer platforms, venture capital insight, market trends, regulatory issues, ethical and societal implications, philanthropic opportunities, medical tourism challenges, cell banking projects, intellectual property landscapes, insurance questions, international perspectives, clinical use and the 2009-10 advocacy agenda.
Blood can be collected from the umbilical cord of a newborn baby shortly after birth. This blood is rich in blood stem cells that can be used to generate red blood cells and cells of the immune system. Cord Blood stem cells can be used to treat a range of blood disorders and immune system conditions such as leukaemia, anaemia and autoimmune diseases. Once collected, cord blood can be stored in a cord blood bank and would be available for use by the donor and compatible siblings.
Alternatively, the cord blood may be donated to a general cord blood bank for use by other tissue matched individuals in need of a transplant. It is hoped that over time a store of cord blood stem cells from people of different tissue types may be established. Someone requiring a transplant would be treated with stem cells from the sample most closely matching their own tissue type, thus minimising complications associated with immune rejection.
Cord blood stem cells may also be useful for treatment of diseases other than blood disorders. Preliminary research reports suggest that cord blood stem cells may have a greater ability to differentiate into different cell types than was previously thought possible. Using animal model, several research groups have used human cord blood stem cells to treat heart attacks and repair injured blood vessels. However, this research is at a very early stage. Scientists are presently unsure whether the cord blood stem cells are transformed into heart muscle or blood vessels, or if they secrete growth factors, that trigger repair. If further studies and clinical trials prove successful, cord blood stem cells may provide a new treatment for cardiovascular disease with fewer side effects than current drug based and surgical treatments.
Ethical Issues
The use of cord blood stem cells in cell-based therapies for blood and immune diseases, and for other potential applications, would be welcomed by the majority of the community. Although cord blood stem cells are less versatile than Embryonic Stem cells, their use in research is less controversial as it does not involve the destruction of embryos. Their potential use for cell-based therapies is also attractive as it would be possible to use a patient’s own cord blood stem cells to generate tissue for transplantation, thus avoiding problems with immune rejection.
.Saviour Siblings
Controversy has arisen over the practice of genetically selecting embryos created during infertility treatment, for the purpose of using the donor baby’s cord blood to treat an ill sibling. In this procedure, genetic testing is performed to ensure that the embryo will provide cord blood devoid of the genetic defect afflicting the sibling, but which matches the sibling’s genetic make up. The donor baby in this case is sometimes referred to as a ‘savior sibling’.
The first ‘saviour sibling’ to be born in Australia was reported in March 2004. A Tasmanian couple used this technology to have a second child who was free of a genetic condition, Hyper IgM Syndrome. Cord blood from this child could be used to treat the affected sibling. As a result of this selection process carried out Sydney IVF Clinic, the woman started her pregnancy knowing that her baby was free of Hyper IgM Syndrome and would be a potential tissue donor for her existing son.
The creation of ‘saviour siblings’ has evoked a quite heated debate in both the medical and general community. Some are vehemently opposed to this application, considering this the first step in ‘designer babies’. Others consider it highly unethical not to use this technology to help the sick sibling. The overarching issue to be considered is the well being of the ‘savior sibling’, and to ask the question whether they will be disadvantaged by the procedure. These are questions to be considered by both the biomedical and general community when considering applications of any new technology.
What is Therapeutic Cloning?
When people think of the word ‘cloning’ they are often hit with frightening images of duplicate human beings being created in somewhat of a mad scientist style experiment. In fact, many members of the public were outraged when Dolly the sheep resulted from a cloning experiment in Scotland. Therapeutic cloning, however, is entirely different and does not involve the creation of a perfectly copied human being. It is reproductive cloning that results in a copy of a specific human being. In therapeutic cloning, no sperm fertilisation is involved nor is there implantation into the uterus to create a child.
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How is Therapeutic Cloning Performed?
Therapeutic cloning is another phrase for a procedure known as somatic cell nuclear transfer (SCNT). In this procedure, a researcher extracts the nucleus from an egg. The nucleus holds the genetic material for a human or laboratory animal. Scientists then take a somatic cell, which is any body cell other than an egg or sperm, and also extract the nucleus from this cell. In practical human applications, the somatic cell would be taken from a patient who requires a stem cell transplant to treat a health condition or disease.
The nucleus that is extracted from the somatic cell in the patient is then inserted into the egg, which had its nucleus previously removed. In a very basic sense, it’s a procedure of substitution. The egg now contains the patient’s genetic material, or instructions. It is stimulated to divide and shortly thereafter forms a cluster of cells known as a blastocyst. This blastocyst has both an outer and inner layer of cells and it is the inner layer, called the inner cell mass that is rich in stem cells. The cells in the inner cell mass are isolated and then utilised to create embryonic stem cell lines, which are infused into the patient where they are ideally integrated into the tissues, imparting structure and function as needed.
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Benefits of Therapeutic Cloning
A major benefit of therapeutic cloning is that the cells removed are pluripotent.
Pluripotent cells can give rise to all cells in the body with the exception of the embryo. This means that pluripotent cells can potentially treat diseases in any body organ or tissue by replacing damaged and dysfunctional cells. Another distinct advantage to this type of therapy is that the risk of immunological rejection is alleviated because the patient’s own genetic material is used. If a cell line were created with cells from another individual, the patient’s body would be more likely to recognise the foreign proteins and then wage an attack on the transplanted cells. The ultimate consequence would be a rejected stem cell transplant. This is one of the major challenges of organ transplants, alongside the fact that there is a huge shortage of available organs for those who require the procedure. This means that therapeutic cloning has the potential to dramatically reduce the wait times for organ transplants as well as the immunological concerns associated with organ transplant therapy.
Therapeutic cloning is also important to enhancing our understanding of stem cells and how they and other cells develop. This understanding can hopefully lead to new treatments or cures for some of the common diseases affecting people today. In addition, the procedure would allow for scientists to create stem cell therapies that are patient specific and perfectly matched for the patient’s medical condition.
Problems with Therapeutic Cloning
One problem with therapeutic cloning is that many attempts are often required to create a viable egg. The stability of the egg with the infused somatic nucleus is poor and it can require hundreds of attempts before success is attained.
Therapeutic cloning does result in the destruction of an embryo after stem cells are extracted and this destruction has stirred controversy over the morality of the procedure. Some argue that the pros outweigh the cons with regards to treating disease whilst others have likened the destruction to an abortion. Still others state that this doesn’t change the fact the embryo could potentially be a human being and so destruction of the embryo is no different than destruction of a human life.
Because reproductive cloning does utilise SCNT as the primary step, there is also still fear that given our knowledge base to perform reproductive cloning, a scientist may attempt to move beyond therapeutic cloning to creation of a human being.
To this date, no human being has been successfully cloned but the possibility of this occurring is a frightening one not only for the general public and policy makers, but also for most of the ethical scientific field. The majority of scientists are adamantly opposed to reproductive cloning and instead, support therapeutic cloning for treating disease. With policies and careful monitoring in place to ensure that therapeutic cloning is used responsibly, we can all benefit from the potential of this procedure to eventually treat, or perhaps one day cure, many diseases.
It is widely accepted that stem cells are involved in tissue regeneration. It is also widely accepted that (in most organs) stem cells are vanishingly rare. So: if there doesn’t happen to be a stem cell adjacent to a site of damage, how can stem cells be involved in the process of tissue repair?