Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

被引：36

作者：

Liu, Yang ^{[1
,2
]}

Jiang, Xiaohua ^{[1
,3
]}

Zhang, Xiaohu ^{[1
]}

Chen, Rui ^{[1
]}

Sun, Tingting ^{[1
]}

Fok, Kin Lam ^{[1
]}

Dong, Jianda ^{[1
]}

Tsang, Lai Ling ^{[1
]}

Yi, Shaoqiong ^{[4
]}

Ruan, Yechun ^{[1
]}

Guo, Jinghui ^{[1
]}

Yu, Mei Kuen ^{[1
]}

Tian, Yuemin ^{[1
]}

Chung, Yiu Wa ^{[1
]}

Yang, Mo ^{[5
]}

Xu, Wenming ^{[1
,6
]}

Chung, Chin Man ^{[1
]}

Li, Tingyu ^{[2
]}

Chan, Hsiao Chang ^{[1
,3
,6
]}

机构：

[1] Chinese Univ Hong Kong, Epithelial Cell Biol Res Ctr, Sch Biomed Sci, Fac Med, Shatin, Hong Kong, Peoples R China

[2] Chongqing Med Univ, Childrens Hosp, Chongqing, Peoples R China

[3] Chinese Univ Hong Kong, Minist Educ, Key Lab Regenerat Med, Jinan Univ, Guangzhou, Guangdong, Peoples R China

[4] Acad Mil Med Sci, Inst Microbiol & Epidemiol, Dept Appl Mol Biol, Beijing, Peoples R China

[5] So Med Univ, Nanfang Hosp, Dept Hematol, Guangzhou, Guangdong, Peoples R China

[6] Sichuan Univ, W China Womens & Childrens Hosp, Minist Educ,Chinese Univ Hong Kong,Key Lab Reprod, Key Lab Obstet Gynecol & Pediat Dis & Birth Defea, Chengdu 610064, Peoples R China

来源：

STEM CELLS | 2011年 / 29卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Dedifferentiation; Reprogramming; miRNA-34a; Enhanced survival; Mesenchymal stem cells; MARROW STROMAL CELLS; NEURAL-LIKE CELLS; BONE-MARROW; RAT; DIFFERENTIATION; GENERATION; APOPTOSIS; GENES; EXPRESSION; PLASTICITY;

D O I：

10.1002/stem.764

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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. STEM CELLS 2011;29:2077-2089

引用

页码：2077 / 2089

页数：13

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