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Adult Stem Cells from Bone Marrow Offer Therapy for Skin Disorder

MarketWatch.com, December 4, 2008

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

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

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

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

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

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

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

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



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