Efficient Direct Lineage Reprogramming of Fibroblasts into Induced Cardiomyocytes Using Nanotopographical Cues

被引：11
作者：
Yoo, Junsang [1 ]
Chang, Yujung [1 ]
Kim, Hongwon [1 ]
Baek, Soonbong [1 ]
Choi, Hwan [1 ]
Jeong, Gun-Jae [2 ]
Shin, Jaein [1 ]
Kim, Hongnam [3 ]
Kim, Byung-Soo [2 ,4 ]
Kim, Jongpil [1 ]
机构：
[1] Dongguk Univ, Dept Biomed Engn, Lab Stem Cells & Cell Reprogramming, Plus Team BK21, Seoul 100715, South Korea
[2] Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 151744, South Korea
[3] Korea Inst Sci & Technol, Brain Sci Inst, Ctr BioMicrosyst, Seoul 136791, South Korea
[4] Seoul Natl Univ, BioMAX Inst, Inst Chem Proc, Seoul 151744, South Korea
来源：
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY | 2017年 / 13卷 / 03期
关键词：
Direct Lineage Reprogramming; Induced Cardiomyocytes; Nanotopographical Cues; EMBRYONIC STEM-CELLS; FOCAL ADHESION KINASE; MOUSE FIBROBLASTS; BIOPHYSICAL REGULATION; EXTRACELLULAR-MATRIX; DOPAMINERGIC-NEURONS; CARDIAC FIBROBLASTS; PLURIPOTENT STATE; DEFINED FACTORS; NUCLEAR SHAPE;
D O I：
10.1166/jbn.2017.2347
中图分类号：
TB3 [工程材料学];
学科分类号：
0805 ; 080502 ;
摘要：
Induced cardiomyocytes (iCMs) generated via direct lineage reprogramming offer a novel therapeutic target for the study and treatment of cardiac diseases. However, the efficiency of iCM generation is significantly low for therapeutic applications. Here, we show an efficient direct conversion of somatic fibroblasts into iCMs using nanotopographic cues. Compared with flat substrates, the direct conversion of fibroblasts into iCMs on nanopatterned substrates resulted in a dramatic increase in the reprogramming efficiency and maturation of iCM phenotypes. Additionally, enhanced reprogramming by substrate nanotopography was due to changes in the activation of focal adhesion kinase and specific histone modifications. Taken together, these results suggest that nanotopographic cues can serve as an efficient stimulant for direct lineage reprogramming into iCMs.
引用
收藏
页码：269 / 279
页数：11
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