title: Dedifferentiation-reprogrammed mesenchymal stem cells with improved therapeutic potential.
abstract: Stem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low in vivo survival and differentiation potential of the transplanted cells limits their overall effectiveness and thus clinical usage. Here we show that, after in vitro induction of neuronal differentiation and dedifferentiation, on withdrawal of extrinsic factors, mesenchymal stem cells (MSCs) derived from bone marrow, which have already committed to neuronal lineage, revert to a primitive cell population (dedifferentiated MSCs) retaining stem cell characteristics but exhibiting a reprogrammed phenotype distinct from their original counterparts. Of therapeutic interest, the dedifferentiated MSCs exhibited enhanced cell survival and higher efficacy in neuronal differentiation compared to unmanipulated MSCs both in vitro and in vivo, with significantly improved cognition function in a neonatal hypoxic-ischemic brain damage rat model. Increased expression of bcl-2 family proteins and microRNA-34a appears to be the important mechanism giving rise to this previously undefined stem cell population that may provide a novel treatment strategy with improved therapeutic efficacy.
authors: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong.
authors: Yang
authors: Y
authors: Liu
authors: Xiaohua
authors: X
authors: Jiang
authors: Xiaohu
authors: X
authors: Zhang
authors: Rui
authors: R
authors: Chen
authors: Tingting
authors: T
authors: Sun
authors: Kin Lam
authors: KL
authors: Fok
authors: Jianda
authors: J
authors: Dong
authors: Lai Ling
authors: LL
authors: Tsang
authors: Shaoqiong
authors: S
authors: Yi
authors: Yechun
authors: Y
authors: Ruan
authors: Jinghui
authors: J
authors: Guo
authors: Mei Kuen
authors: MK
authors: Yu
authors: Yuemin
authors: Y
authors: Tian
authors: Yiu Wa
authors: YW
authors: Chung
authors: Mo
authors: M
authors: Yang
authors: Wenming
authors: W
authors: Xu
authors: Chin Man
authors: CM
authors: Chung
authors: Tingyu
authors: T
authors: Li
authors: Hsiao Chang
authors: HC
authors: Chan
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D002470:Cell Survival; D002552:Cerebral Ventricles / Q000378:metabolism; D018920:Coculture Techniques; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020925:Hypoxia-Ischemia, Brain / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D006861:Hydrogen Peroxide