Three-dimensional collagenous niche and azacytidine selectively promote time-dependent cardiomyogenesis from human bone marrow-derived MSC spheroids
Three-dimensional collagenous niche and azacytidine selectively promote time-dependent cardiomyogenesis from human bone marrow-derived MSC spheroids
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DOI：
10.1002/bit.26714
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发表时间：
2018-08-01
影响因子：
3.8
通讯作者：
Kothapalli, Chandrasekhar R.
中科院分区：
文献类型：
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作者：
Joshi, Jyotsna;Mahajan, Gautam;Kothapalli, Chandrasekhar R.
内源性成人心脏再生机制不能取代心肌梗死后丢失的细胞，往往导致结构-功能-力学特性的永久性改变。基于在适当的3D环境中递送自体干细胞的再生疗法可以通过使移植细胞归巢和定向分化为丢失的特化细胞群来满足这种需求。由于I型胶原是主要的心脏组织基质蛋白，我们在这里优化的3D生态位，可以促进时间依赖性进化的心肌细胞从人骨髓来源的间充质干细胞（BM-MSC）。分别使用扫描电子显微镜和原子力显微镜评估3D胶原凝胶的物理和机械特征，同时使用免疫荧光标记和RT-PCR分析量化胶原浓度、培养时间和5-氮杂胞苷（aza）剂量对MSC球体表型和基因型的单独和综合影响。增加胶原蛋白浓度导致杨氏模量显著增加（p
Endogenous adult cardiac regenerative machinery is not capable of replacing the lost cells following myocardial infarction, often leading to permanent alterations in structure-function-mechanical properties. Regenerative therapies based on delivering autologous stem cells within an appropriate 3D milieu could meet such demand, by enabling homing and directed differentiation of the transplanted cells into lost specialized cell populations. Since type I collagen is the predominant cardiac tissue matrix protein, we here optimized the 3D niche which could promote time-dependent evolution of cardiomyogenesis from human bone marrow-derived mesenchymal stem cells (BM-MSC). 3D collagen gel physical and mechanical characteristics were assessed using SEM and AFM, respectively, while the standalone and combined effects of collagen concentration, culture duration, and 5-azacytidine (aza) dose on the phenotype and genotype of MSC spheroids were quantified using immunofluorescence labeling and RT-PCR analysis. Increasing collagen concentration led to a significant increase in Young's modulus (p