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

doi:10.1002/stem.764

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 publication › Journal article › Academic research › peer-review

38 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 language	English
Pages (from-to)	2077-2089
Number of pages	13
Journal	Stem Cells
Volume	29
Issue number	12
DOIs	https://doi.org/10.1002/stem.764
Publication status	Published - 1 Dec 2011
Externally published	Yes

Keywords

Dedifferentiation
Enhanced survival
Mesenchymal stem cells
MiRNA-34a
Reprogramming

ASJC Scopus subject areas

Molecular Medicine
Developmental Biology
Cell Biology

More information

10.1002/stem.764

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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 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.",

keywords = "Dedifferentiation, Enhanced survival, Mesenchymal stem cells, MiRNA-34a, Reprogramming",

author = "Yang Liu and Xiaohua Jiang and Xiaohu Zhang and Rui Chen and Tingting Sun and Fok, {Kin Lam} and Jianda Dong and Tsang, {Lai Ling} and Shaoqiong Yi and Yechun Ruan and Jinghui Guo and Yu, {Mei Kuen} and Yuemin Tian and Chung, {Yiu Wa} and Mo Yang and Wenming Xu and Chung, {Chin Man} and Tingyu Li and Chan, {Hsiao Chang}",

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doi = "10.1002/stem.764",

language = "English",

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pages = "2077--2089",

journal = "Stem Cells",

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TY - JOUR

T1 - Dedifferentiation-reprogrammed mesenchymal stem cells with improved therapeutic potential

AU - Liu, Yang

AU - Jiang, Xiaohua

AU - Zhang, Xiaohu

AU - Chen, Rui

AU - Sun, Tingting

AU - Fok, Kin Lam

AU - Dong, Jianda

AU - Tsang, Lai Ling

AU - Yi, Shaoqiong

AU - Ruan, Yechun

AU - Guo, Jinghui

AU - Yu, Mei Kuen

AU - Tian, Yuemin

AU - Chung, Yiu Wa

AU - Yang, Mo

AU - Xu, Wenming

AU - Chung, Chin Man

AU - Li, Tingyu

AU - Chan, Hsiao Chang

PY - 2011/12/1

Y1 - 2011/12/1

N2 - 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.

AB - 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.

KW - Dedifferentiation

KW - Enhanced survival

KW - Mesenchymal stem cells

KW - MiRNA-34a

KW - Reprogramming

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DO - 10.1002/stem.764

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C2 - 22052697

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ER -

Dedifferentiation-reprogrammed mesenchymal stem cells with improved therapeutic potential

Abstract

Keywords

ASJC Scopus subject areas

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