Treatment of Hereditary Epidermolysis Bullosa: Updates and Future Prospects

Chao-Kai Hsu; Sheng-Pei Wang; Julia Yu-Yun Lee; John A. McGrath

Disclosures

Am J Clin Dermatol. 2014;15(1):1-6. 

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5 Intradermal Injection of Mesenchymal Stromal Cells

Intradermal injections of bone marrow-derived mesenchymal stromal cells (MSCs) have been assessed in two individuals with RDEB.[23] This study showed improved wound healing following injection of 0.5 x 106 allogeneic MSCs compared with saline. In contrast to allogeneic fibroblasts, allogeneic MSCs appeared to be able to induce de novo synthesis of basement membrane C7. Clinicopathologic improvements were sustained for 4 months, after which the original skin fragility and pathology returned. Recent murine studies by Tamai et al.[24] have shown that the MSC pool in bone marrow contains a subpopulation of cells that include epithelial progenitors. These MSCs, which are platelet-derived growth factor receptor-alpha (PDGFR α)-positive and Lineage-negative, are recruited to damaged skin along a concentration gradient of the tissue distress factor high mobility group box-1 (HMGB1) that is rapidly released from hypoxic keratinocytes in RDEB blister roofs. Future clinical trials in RDEB are likely to target and exploit this population of MSCs and the HMGB1 recruitment factor. Intravenous clinical trials of bone marrow-derived MSCs and adipose-derived MSCs are also entering early clinical trials in Egypt, Chile, the UK, and Brazil. Although these cells are not tissue matched, it is hoped that the MSCs will trigger a systemic antiinflammatory trophic benefit (modifying T cells and B cells and upregulating cytokines such as interleukin-10) that may lead to clinical benefits for several months.

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