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Microdystrophin Delivery in Dystrophin-Deficient (mdx) Mice by Genetically-Corrected Syngeneic MSCs Transplantation.

150 150 NZ Stem Cell Treatment Centre

2010 Sep; 42(7) : 2731-9
Microdystrophin Delivery in Dystrophin-Deficient (mdx) Mice by Genetically-Corrected Syngeneic MSCs Transplantation.
Xiong F, Xu Y, Zheng H, Lu X, Feng S, Shang Y, Li Y, Zhang Y, Jin S, Zhang C

Abstract
Cell transplantation and gene therapy are two promising therapeutical approaches for the treatment on Duchenne Muscular Dystrophy (DMD). However, both strategies have met many hurdles, mainly because of the absence of an efficient systemic delivery system on gene therapy and immune reactions on cell transplantation. In this project, we investigated the strategy based on combination of these two basic ones, i.e., transplantation of transgene-corrected mdx mesenchymal stem cells (MSCs) into mdx mice to cure DMD. The MSCs isolated from male mdx mice were transduced with recombinant adenovirus including human microdystrophin gene and labeled with BrdU were transplanted into female mdx mice, the Chimerism with the sex determinant Y chromosome and human microdystrophin expression were detected. Simultaneously, the plasma creatine kinase (CK) activity, the improvement with the muscles’ pathology and contractile properties were evaluated. The results clearly demonstrated that some human dystrophin and BrdU expression collectively were detected in some muscles of transplanted mdx mice. Moreover, the CK activity and percentage of centrally nucleated fiber (CNF) decreased slightly after transplanation. Regrettably, the protective effect on contractioninduced injury in TA and diaphragm muscles wasn’t significantly improvement after transplantation. Our results suggested, if enhancement on the efficiency with cell transplantation, that the transplantation of autologous MSCs corrected by dystrophin may be a form to treat DMD patients in future.

PMID: 20832578 [PubMed – in process]