A naturally derived cardiac extracellular matrix enhances cardiac progenitor cell behavior in vitro.

A naturally derived cardiac extracellular matrix enhances cardiac progenitor cell behavior in vitro.
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DOI:
10.1016/j.actbio.2012.07.033
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发表时间:
2012-12
期刊:
影响因子:
9.7
通讯作者:
Davis, Michael E.
Davis, Michael E.
中科院分区:
工程技术1区
文献类型:
--
作者:
French, Kristin M.;Boopathy, Archana V.;DeQuach, Jessica A.;Chingozha, Loice;Lu, Hang;Christman, Karen L.;Davis, Michael E.

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心肌梗死(MI)产生胶原瘢痕,改变局部微环境并阻碍心脏功能。细胞疗法是一种有前途的治疗选择,以取代心肌梗死后失去的数十亿个肌细胞。尽管早期成功,但慢性功能仍然受损,可能是细胞保留、增殖和分化/成熟不良的结果。虽然一些用支架递送细胞的努力试图解决这些缺点,但它们缺乏最佳细胞功能所需的天然线索。本研究的目的是确定天然来源的心脏细胞外基质(cECM)是否可以在体外增强心脏祖细胞(CPC)的功能。通过c-kit+细胞的磁性分选分离CPC,并在用cECM或胶原I(COL)包被的板上生长。我们的研究结果显示,与COL相比,cECM上的早期心肌细胞标志物增加,以及随后相应的蛋白质表达。与COL相比,CPC在cECM上显示出更强的血清诱导的增殖,以及血清饥饿后对凋亡的抗性增加。最后,一个微流控粘附试验表明,更强的粘附CPC与cECM相比,COL。这些数据表明,cECM可能是最佳的CPC治疗交付,以及裸细胞治疗的缺点提供了潜在的机制。
Myocardial infarction (MI) produces a collagen scar, altering the local microenvironment and impeding cardiac function. Cell therapy is a promising therapeutic option to replace the billions of myocytes lost following MI. Despite early successes, chronic function remains impaired and is likely a result of poor cellular retention, proliferation, and differentiation/maturation. While some efforts to deliver cells with scaffolds attempt to address these shortcomings, they lack the natural cues required for optimal cell function. The goal of this study was to determine whether a naturally-derived cardiac extracellular matrix (cECM) could enhance cardiac progenitor cell (CPC) function in vitro. CPCs were isolated via magnetic sorting of c-kit+ cells and were grown on plates coated with either cECM or collagen I (COL). Our results show an increase in early cardiomyocyte markers on cECM compared to COL, as well as corresponding protein expression later. CPCs show stronger serum-induced proliferation on cECM as compared to COL, as well as increased resistance to apoptosis following serum-starvation. Finally, a microfluidic adhesion assay demonstrated stronger adhesion of CPCs to cECM compared with COL. These data suggest that cECM may be optimal for CPC therapeutic delivery, as well as provide potential mechanisms for the shortcomings in naked cell therapy.
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