Muscle tissue engineering and regeneration through epigenetic reprogramming and scaffold manipulation.
Muscle tissue engineering and regeneration through epigenetic reprogramming and scaffold manipulation.
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通过表观遗传学重编程和支架操作实现肌肉组织工程和再生。
DOI：
10.1038/srep16333
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发表时间：
2015-11-09
影响因子：
4.6
通讯作者：
Han B
中科院分区：
文献类型：
--
作者：
Tan SJ;Fang JY;Wu Y;Yang Z;Liang G;Han B
由于细胞老化和细胞相互作用的可控性较差，细胞对损伤的反应不足，限制了基于细胞的组织工程和再生医学的效率。由于细胞的进展受到严格的表观遗传调控，5-氮杂胞苷（5-Aza-CR）等表观遗传调节剂已被用于促进二维（2-D）环境下体细胞的重编程和发育。尽管如此，特定组织谱系向终端表型的进展不仅依赖于基因组潜力，而且还依赖于超出二维方法能力的微环境线索。在这项研究中，我们在体外和体内研究了可变刚度基质和表观遗传调节剂5-Aza-CR对利用可调谷氨酰胺转胺酶交联明胶（Col-Tgel）将脂肪源性基质细胞（ADSCs）重编程为成肌细胞样细胞的联合作用。我们的实验表明，在最佳肌原基质（15±5 kPa coll - tgel）中，用有效剂量的5- aza - cr （1.25 ~ 12.5 ng）处理ADSCs后，细胞可塑性和反式分化显著增强。我们的发现表明，物理信号和化学环境对细胞反应的调节都是至关重要的。
Efficiency of cell-based tissue engineering and regenerative medicine has been limited by inadequate cellular responses to injury because of aging and poor controllability of cellular interactions. Since cell progression is under a tight epigenetic regulation, epigenetic modulators such as 5-azacytidine (5-Aza-CR) have been utilized to facilitate reprogramming and development of somatic cells in 2-dimensional (2-D) settings. Nonetheless, progression of a specific tissue lineage toward the terminal phenotype is dependent not only on the genomic potential, but also on the microenvironment cues that are beyond the capability of 2-D approaches. In this study, we investigated the combined effects of matrices of variable rigidities and the treatment with the epigenetic modulator 5-Aza-CR on reprogramming adipose-derived stromal cells (ADSCs) into myoblast-like cells by utilizing tunable transglutaminase cross-linked gelatin (Col-Tgel) in vitro and in vivo. Our experiments demonstrated that cellular plasticity and trans-differentiation were significantly enhanced when ADSCs were treated with an effective dose of 5-Aza-CR (1.25 to 12.5 ng) in the optimal myogenic matrix (15 ± 5 kPa Col-Tgel). Our findings suggest that both physical signals and chemical milieu are critical for the regulation of cellular responses.