Microscale generation of cardiospheres promotes robust enrichment of cardiomyocytes derived from human pluripotent stem cells.
Microscale generation of cardiospheres promotes robust enrichment of cardiomyocytes derived from human pluripotent stem cells.
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DOI：
10.1016/j.stemcr.2014.06.002
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发表时间：
2014-08-12
影响因子：
5.9
通讯作者：
Xu, Chunhui
中科院分区：
文献类型：
--
作者：
Nguyen, Doan C.;Hookway, Tracy A.;Wu, Qingling;Jha, Rajneesh;Preininger, Marcela K.;Chen, Xuemin;Easley, Charles A.;Spearman, Paul;Deshpande, Shriprasad R.;Maher, Kevin;Wagner, Mary B.;McDevitt, Todd C.;Xu, Chunhui
来源于人多能干细胞（hPSC）的心肌细胞是再生医学、疾病建模和药物发现的有前途的细胞来源，所有这些都需要富集的心肌细胞，理想的是具有成熟表型的心肌细胞。然而，目前的方法通常是在2D环境中进行的，在异质群体中产生不成熟的心肌细胞。在这里，我们使用微尺度技术和旋转轨道悬浮培养从hPSC的2D分化培养物产生心肌细胞（心脏球）的3D聚集体。几乎100%的心脏微球表现出自发性收缩和同步的细胞内钙瞬变。引人注目的是，从含有约10%-40%心肌细胞的起始异质群体开始，所产生的心脏球内的细胞群体以约80%-100%心肌细胞为特征，对应于高达7倍的富集因子。此外，心肌细胞从心脏球表现出增强的结构成熟与那些从平行的2D文化。因此，心脏球的产生代表了一种简单而稳健的方法，用于在再生医学以及其他应用中具有潜在用途的微组织中富集心肌细胞。微球能够从人多能干细胞富集心肌细胞即使从具有低心肌细胞纯度的培养物中也可以实现稳健的富集微球还促进心肌细胞结构成熟富集和成熟的心肌细胞对于源自人多能干细胞的心肌细胞的临床翻译是高度期望的。在这份报告中，Xu，McDevitt及其同事表明，即使在分化效率较低的情况下，心脏球的微尺度形成也能够从分化培养物中稳健地富集心肌细胞。此外，在悬浮培养后的心球中观察到心肌细胞的结构成熟增强。
Cardiomyocytes derived from human pluripotent stem cells (hPSCs) are a promising cell source for regenerative medicine, disease modeling, and drug discovery, all of which require enriched cardiomyocytes, ideally ones with mature phenotypes. However, current methods are typically performed in 2D environments that produce immature cardiomyocytes within heterogeneous populations. Here, we generated 3D aggregates of cardiomyocytes (cardiospheres) from 2D differentiation cultures of hPSCs using microscale technology and rotary orbital suspension culture. Nearly 100% of the cardiospheres showed spontaneous contractility and synchronous intracellular calcium transients. Strikingly, from starting heterogeneous populations containing ∼10%–40% cardiomyocytes, the cell population within the generated cardiospheres featured ∼80%–100% cardiomyocytes, corresponding to an enrichment factor of up to 7-fold. Furthermore, cardiomyocytes from cardiospheres exhibited enhanced structural maturation in comparison with those from a parallel 2D culture. Thus, generation of cardiospheres represents a simple and robust method for enrichment of cardiomyocytes in microtissues that have the potential use in regenerative medicine as well as other applications. Cardiospheres enable enrichment of cardiomyocytes from human pluripotent stem cells Robust enrichment can be achieved even from cultures with low cardiomyocyte purity Cardiospheres also promote cardiomyocyte structural maturation Enriched and mature cardiomyocytes are highly desirable for the clinical translation of cardiomyocytes derived from human pluripotent stem cells. In this report, Xu, McDevitt, and colleagues show that microscale formation of cardiospheres enables robust enrichment of cardiomyocytes from differentiation cultures, even when differentiation efficiency is low. In addition, enhanced structural maturation of cardiomyocytes is observed in cardiospheres following suspension culture.
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