Bone Marrow-Derived Stem Cells Migrate into Intra-epidermal Skin Defects of a Desmoglein-3 knockout Mouse Model but Preserve their Mesodermal Differentiation.
Journal of Investigative Dermatology(2018)
摘要
Inherited forms of Epidermolysis bullosa (EB) are blistering diseases of the skin and mucosa resulting from various gene mutations. Transplantation of bone marrow (BM)-derived stem cells might be a promising systemic treatment for severe dystrophic or junctional EB, but many key questions remain unresolved. Two open questions of clinical interest are whether systemically transplanted BM-derived stem cells of mesodermal origin might be able to transdifferentiate into keratinocytes with an ectodermal phenotype and whether these cells are also capable of repairing a specific intra-epidermal gene defect. To address these questions, we transplanted BM-derived stem cells into mice with a blistering disease exclusively localized to the epidermis resulting from a functional knockout of desmoglein-3 (Dsg3). We found that Dsg3+ donor-derived cells migrate into the recipient epidermis. However, these cells failed to restore the missing Dsg3 mRNA and DSG3 protein expression in the transplanted Dsg3-/- mice. The donor-derived cells found in the epidermis preserved their CD45+ haematopoietic origin, and no trans-differentiation into integrin α6+ keratinocytes or integrin α6+/CD34+ epidermal stem cells occurred. Our results indicate that BM-derived stem cells preserve their mesodermal fate after systemic transplantation and are not capable of treating EB patients with an intra-epidermal skin defect.
更多查看译文
关键词
BMC,BMT,Dsg3,EB,HSC,JEB,MSC,PBS,RDEB
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要