Efficient Generation of Chemically Induced Mesenchymal Stem Cells from Human Dermal Fibroblasts

被引:25
作者
Lai, Pei-Lun [1 ,2 ]
Lin, Hsuan [3 ,4 ]
Chen, Shang-Fu [2 ,5 ,6 ]
Yang, Shang-Chih [2 ]
Hung, Kuo-Hsuan [2 ]
Chang, Ching-Fang [2 ]
Chang, Hsiang-Yi [1 ]
Lu, Frank Leigh [3 ,4 ]
Lee, Yi-Hsuan [2 ]
Liu, Yu-Chuan [2 ]
Huang, Hsiao-Chun [1 ,5 ,6 ,7 ]
Lu, Jean [1 ,2 ,8 ,9 ]
机构
[1] Natl Taiwan Univ, Coll Life Sci, Genome & Syst Biol Degree Program, Taipei, Taiwan
[2] Acad Sinica, Genom Res Ctr, Taipei, Taiwan
[3] Natl Taiwan Univ Hosp, Dept Pediat, Taipei, Taiwan
[4] Natl Taiwan Univ, Coll Med, Taipei, Taiwan
[5] Natl Taiwan Univ, Coll Life Sci, Inst Mol & Cellular Biol, Taipei, Taiwan
[6] Natl Taiwan Univ, Coll Life Sci, Dept Life Sci, Taipei, Taiwan
[7] Natl Taiwan Univ, Coll Elect Engn & Comp Sci, Grad Inst Elect Engn, Taipei, Taiwan
[8] Natl Core Facil Program Biotechnol, Natl RNAi Platform, Taipei, Taiwan
[9] Tzu Chi Univ, Dept Life Sci, Hualien, Taiwan
关键词
ACUTE LUNG INJURY; BONE-MARROW; OSTEOGENIC DIFFERENTIATION; MOUSE FIBROBLASTS; SOMATIC-CELLS; STROMAL CELLS; STATE; MSCS; CARDIOMYOCYTES; PROLIFERATION;
D O I
10.1038/srep44534
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Human mesenchymal stromal/stem cells (MSCs) are multipotent and currently undergoing hundreds of clinical trials for disease treatments. To date, no studies have generated induced MSCs from skin fibroblasts with chemicals or growth factors. Here, we established the first chemical method to convert primary human dermal fibroblasts into multipotent, induced MSC-like cells (iMSCs). The conversion method uses a defined cocktail of small molecules and growth factors, and it can achieve efficient conversion with an average rate of 38% in 6 days. The iMSCs have much higher clonogenicity than fibroblasts, and they can be maintained and expanded in regular MSC medium for at least 8 passages and further differentiated into osteoblasts, adipocytes, and chondrocytes. Moreover, the iMSCs can suppress LPS-mediated acute lung injury as effectively as bone marrow-derived mesenchymal stem cells. This finding may greatly benefit stem cell biology, cell therapy, and regenerative medicine.
引用
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页数:13
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