Human stem cells promote healing of diabetic ulcersApril 21, 2009Treatment of chronic wounds is a continuing clinical problem and socio-economic burden with diabetic foot ulcers alone costing the NHS £300 million a year. Scientists in Bristol have found that human foetal stem cells can effectively be used to treat back leg ischaemic ulcers in a model of type 1 diabetes. The researchers also found the culture in which the stem cells had been grown mimicked the wound-healing ability of the cells, suggesting that they could be used as a "factory" of wound-healing substances. Alternatively, the active ingredients in the culture, once identified, could be used instead; this would avoid the ethical concerns of using human foetal stem cells. In humans, diabetic patients with ischaemic foot ulcers have the worst outcome of all chronic skin wounds, with higher amputation and mortality rates than patients carrying non-ischaemic ulcers. Topical gels containing single growth factors have recently been used with some success in non-ischaemic ulcers, but have been unsuccessful in ischaemic ulcers, which are also resistant to other conventional treatment. Ischaemia results when the blood supply to a tissue is greatly reduced or stopped - this can occur in diabetes since it can also cause impaired blood flow in patients. The healing activity of stem cells is recognised for their ability to separate into the various component cells of injured tissues, as well as to discharge growth factors that may encourage the formation of new blood vessels in the patient. Paolo Madeddu, Professor of Experimental Cardiovascluar Medicine and colleagues at the Bristol Heart Institute, previously used stem cells in models of back leg ischaemia, showing that foetal stem cells could be more therapeutically effective than adult stem cells. Foetal stem cells possess a better ability to multiply and to graft onto host tissue, and to separate into other cell types to replace those in the damaged tissue. The group led by Bristol University's Professor Madeddu have found that foetal stem cells accelerate the closure of ischaemic diabetic ulcers, while stem cells from blood of adult donors are ineffective. Professor Madeddu, commenting on the research, said: "This is the first study to demonstrate the healing capacity of local therapy with CD133+ stem cells in a model of diabetic ischaemic foot ulcer. The foetus-derived cells would be difficult to obtain for therapeutic applications. However, the finding that conditioned culture is also effective in stimulating wound healing may have important implications for the cure of the ischaemic complications of diabetes. "Foetal CD133+ cells might be used in the future as a "factory" of therapeutic substances. Alternatively, synthetic replica of the conditioned medium could be produced to obviate ethical concerns surrounding the direct use of foetal stem cells." Karen Addington, Chief Executive of Juvenile Diabetes Research Foundation (JDRF), added: "Chronic wounds and diabetic foot ulcers are serious long-term complications of type 1 diabetes. Because of the difficulties involved in managing type 1 diabetes, people living with the condition are at an increased risk of requiring a non-traumatic limb amputation. Although more work needs to be done before we can begin to think about potential new treatments, this research represents a useful way to help identify new strategies for dealing with type 1 diabetes." The researchers discovered that a particular type of stem cell -- CD133+ cells (derived from human foetal aorta) promoted blood vessel formation in order to salvage the diabetic limb. Three days following the graft consisting of collagen plus CD133+ cells, hardly any CD133+ cells were detected in the ischaemic diabetic ulcer -- indicating that transplanted cells had done their task in the very first days after transplantation possibly by boosting the generation of new vessels through an indirect mechanism. They found that the CD133+ cells released large amount of growth factors and cytokines endowed of pro-angiogenic and pro-survival potential. To confirm the importance of these released factors, Professor Madeddu and colleagues have grown the CD133+ cells in vitro, and then used the "conditioned" culture to reproduce the effects on wound healing and angiogenesis. These additional experiments confirmed that wound healing and angiogenesis are equally benefited either by giving stem cells or the stem cells' released product. In the attempt to explain which component of the healing cocktail were really important, they withdrew likely candidates one by one by blocking antibodies. Interestingly, they found that the vascular endothelial growth factor A (VEFG-A) and some interleukins were the crucial factors accounting for the healing effect of transplanted stem cells. Importantly, VEGF-A was recognized to be the responsible for reactivation of foetal genes, belonging to the Wingless gene family, in the wounded tissue. Withdrawal of wingless gene products also prohibited the beneficial action of conditioned medium on the wound closure and reparative angiogenesis. This discovery provides a new perspective in the use of foetal stem cells. It is known that wounds heal so well in foetuses that no scar can be visible at birth. It is therefore possible that, when foetal stem cells are transplanted onto diabetic ulcers, they reactivate a foetal program in the recipient to allow those adult ulcers to repair as efficiently as foetal wounds do. University of Bristol |
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| Related Stem Cells Current Events and Stem Cells News Articles New discovery about the formation of new brain cells The generation of new nerve cells in the brain is regulated by a peptide known as C3a, which directly affects the stem cells' maturation into nerve cells and is also important for the migration of new nerve cells through the brain tissue, reveals new research from the Sahlgrenska Academy published in the journal Stem Cells. Umbilical cord blood stem cell transplant may help lung, heart disorders Two separate studies published in the current issue of Cell Transplantation (18:8), - now freely available on-line have shown that transplanted human-derived umbilical cord blood (UCB) stem cells transplanted in an animal model had positive therapeutic effects on specific lung and heart disorders the animal models. Gene mismatch influences success of bone marrow transplants A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics. New research shows versatility of amniotic fluid stem cells For the first time, scientists have demonstrated that stem cells found in amniotic fluid meet an important test of potential to become specialized cell types, which suggests they may be useful for treating a wider array of diseases and conditions than scientists originally thought. First reconstitution of an epidermis from human embryonic stem cells Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells. Bone Implant Offers Hope for Skull Deformities A synthetic bone matrix offers hope for babies born with craniosynostosis, a condition that causes the plates in the skull to fuse too soon. Your Own Stem Cells Can Treat Heart Disease The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells. Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines? Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure. Paradoxical protein might prevent cancer One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell. U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning. More Stem Cells Current Events and Stem Cells News Articles |
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