Concise Review: Transplantation of Human Hematopoietic Cells for Extracellular Matrix Protein Deficiency in Epidermolysis Bullosa

Abstract

The skin is constantly exposed to environmental insults and requires effective repair processes to maintain its protective function. Wound healing is severely compromised in people with congenital absence of structural proteins of the skin, such as in dystrophic epidermolysis bullosa, a severe congenital mechanobullous disorder caused by mutations in collagen type VII. Remarkably, stem cell transplantation can ameliorate deficiency of this skin-specific structural protein in both animal models and in children with the disorder. Healthy donor cells from the hematopoietic graft migrate to the injured skin; simultaneously, there is an increase in the production of collagen type VII, increased skin integrity, and reduced tendency to blister formation. How hematogenous stem cells from bone marrow and cord blood can alter skin architecture and wound healing in a robust, clinically meaningful way is unclear. We review the data and the resulting hypotheses that have a potential to illuminate the mechanisms for these effects. Further modifications in the use of stem cell transplantation as a durable source of extracellular matrix proteins may make this regenerative medicine approach effective in other cutaneous and extracutaneous conditions. STEM CELLS 2011;29:900-906Disclosure of potential conflicts of interest is found at the end of this article.

Natural Gene Therapy May Occur in All Patients with Generalized Non-Herlitz Junctional Epidermolysis Bullosa with COL17A1 Mutations

“…Patient-specific keratinocytes from revertant mosaic patches that have been corrected spontaneously could be used as a source for patient-specific iPS cells and provide an essentially unlimited number of patient-specific cells for grafting. Alternatively, iPS cells may be differentiated into both hematopoietic and mesenchymal stem cells, which can home into blistered areas of the skin following bone marrow transplantation (Wagner et al, 2010;Tolar et al, 2011a): ''from skin to blood cell to repair skin''. The fact that the majority, if not all, generalized JEB-nH patients with COL17A1 mutations in the Netherlands have revertant keratinocytes makes it even more exciting to explore further therapeutic options with these naturally corrected cells.…”

Molecular Therapeutics for Heritable Skin Diseases

“…Bone marrow transplantation in the children with RDEB was noted to result in synthesis of new type VII collagen and clinical improvement that was sustained for at least 1 year after the transplantation (Wagner et al , 2010; Tolar et al , 2011). Although these preliminary studies were promising and generated cautious optimism, it should be noted that two of the seven children died as a result of complications of the bone marrow transplant procedure, which utilized traditional chemoablative preconditioning of the recipients.…”

Collagen VII plays a dual role in wound healing

“…A feared complication of RDEB is squamous cell carcinoma, which arises at an early age in trauma-prone skin areas (15,16). Although clinical observations suggest that wound closure is impaired in RDEB (19)(20)(21), no study thus far has addressed the role of COL7A1 in wound healing.…”