Dedifferentiation-reprogrammed mesenchymal stem cells with improved therapeutic potential

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

Research output: Journal article publicationJournal articleAcademic researchpeer-review

25 Citations (Scopus)

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 micro-RNA-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.
Original languageEnglish
Pages (from-to)2077-2089
Number of pages13
JournalStem Cells
Volume29
Issue number12
DOIs
Publication statusPublished - 1 Dec 2011
Externally publishedYes

Keywords

  • Dedifferentiation
  • Enhanced survival
  • Mesenchymal stem cells
  • MiRNA-34a
  • Reprogramming

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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