Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

• DOI: 10.1002/stem.764
• Publication Date: 2011-11-03T13:52:25Z
• Authors: Yang Liu; Xiaohua Jiang; Xiaohu Zhang; Rui Chen; Tingting Sun; Kin Lam Fok; Jianda Dong; Lai Ling Tsang; Shaoqiong Yi; Yechun Ruan; Jinghui Guo; Mei Kuen Yu; Yuemin Tian; Yiu Wa Chung; Mo Yang; Wenming Xu; Chin Man Chung; Tingyu Li; Hsiao Chang Chan
• Keywords: Male; Neurons; 0303 health sciences; Cell Survival; Cell Differentiation; Mesenchymal Stem Cells; Hydrogen Peroxide; Cell Dedifferentiation; Mesenchymal Stem Cell Transplantation; Coculture Techniques; Cerebral Ventricles; Rats; MicroRNAs; 03 medical and health sciences; Phenotype; Proto-Oncogene Proteins c-bcl-2; Hypoxia-Ischemia, Brain; Models, Animal; Animals

Abstract Stem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low vivo survival differentiation potential of the transplanted cells limits their overall effectiveness thus clinical usage. Here we show that, after vitro induction neuronal dedifferentiation, on withdrawal extrinsic factors, mesenchymal stem (MSCs) derived from bone marrow, which have already committed lineage, revert a primitive population (dedifferentiated MSCs) retaining characteristics but exhibiting reprogrammed phenotype distinct original counterparts. Of therapeutic interest, dedifferentiated MSCs exhibited enhanced higher efficacy compared unmanipulated both vivo, with significantly improved cognition function neonatal hypoxic–ischemic brain damage rat model. Increased expression bcl-2 family proteins microRNA-34a appears be important mechanism giving rise this previously undefined that may provide novel treatment strategy efficacy.