The debilitating condition is caused by significantly reduced collagen type 7 protein (col7) production, a key component of the anchoring fibrils that connect the cutaneous membranes to the dermis of the skin and mucosal tissues in the gastrointestinal tract.
Currently, there's no cure for the disease, and palliative care includes complex bandaging, surgical removal of damaged tissue, and nutritional support.
"We have been looking into stem cells as viable treatment options for correction of conditions such as epidermolysis bullosa, because they can produce extracellular matrix proteins. 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," said Jakub Tolar, MD, PhD, of the University of Minnesota and lead author of the study.
For the study, the researchers worked with a mouse model of RDEB-infused bone marrow cells to determine if they would increase production of the col7 protein and formation of anchoring fibrils, and improve survival in the mouse recipients.
So, they used bone marrow cells enriched for hematopoietic (stem cells that can develop into most blood cell types) and progenitor cells to increase the concentration of cells with the capacity to produce col7.
They then tested these cells against non-enriched stem cells to determine their benefit to the treated mice.
The results of the study showed that when injected into mice with RDEB, these specially selected marrow-derived stem cells diminished the disease process.
"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 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," said Tolar.
The results indicated that the systemic infusion of wild-type bone marrow cells could provide benefit to other human disorders of the extracellular matrix.
Now scientists are working towards identifying the requirements of bone marrow-derived stem cells capable of efficiently homing to wounded skin and producing an array of extracellular matrix proteins.
Currently, the clinical testing of efficacy of human bone marrow for the treatment of human RDEB is underway to determine whether it is of more substantial benefit than local protein, gene, or cellular therapies currently being investigated by other researchers.
The study was prepublished online in Blood, the official journal of the American Society of Hematology.