Long-term human pluripotent stem cell self-renewal on synthetic polymer surfaces.

Long-term human pluripotent stem cell self-renewal on synthetic polymer surfaces.
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DOI:
10.1016/j.biomaterials.2010.08.007
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发表时间:
2010-12
期刊:
影响因子:
14
通讯作者:
Chien, Shu
Chien, Shu
中科院分区:
工程技术1区
文献类型:
--
作者:
Brafman, David A.;Chang, Chien W.;Fernandez, Antonio;Willert, Karl;Varghese, Shyni;Chien, Shu

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要实现人类多能干细胞(hPSC)在再生医学中的全部潜力,需要为其长期生长和定向分化开发明确的培养条件。目前用于维持hPSC的实践通常利用凭经验确定的饲养细胞和其他基于动物的产品的组合,其昂贵、难以分离、经受批次间变化并且不适合于基于细胞的疗法。使用高通量筛选方法,我们鉴定了几种可以支持hPSC自我更新的聚合物。虽然这些聚合物中的大多数仅在短时间内提供支持,但我们确定了一种合成聚合物聚(甲基乙烯基醚-alt-马来酸酐)(PMVE-alt-MA),其支持HUES 1,HUES 9和iPSC在五代内的附着,增殖和自我更新。在PMVE-alt-MA上培养的hPSC保持其特征性形态,表达高水平的多能性标志物,并保留正常的核型。这种支持hPSC长期自我更新和增殖的具有成本效益的基于聚合物的基质不仅有助于加速hPSC的翻译前景,而且还提供了阐明调节干细胞增殖和分化的潜在分子机制的平台。
Realization of the full potential of human pluripotent stem cells (hPSCs) in regenerative medicine requires the development of well-defined culture conditions for their long-term growth and directed differentiation. Current practices for maintaining hPSCs generally utilize empirically determined combinations of feeder cells and other animal-based products, which are expensive, difficult to isolate, subject to batch-to-batch variations, and unsuitable for cell-based therapies. Using a high-throughput screening approach, we identified several polymers that can support self-renewal of hPSCs. While most of these polymers provide support for only a short period of time, we identified a synthetic polymer poly(methyl vinyl ether-alt-maleic anhydride) (PMVE-alt-MA) that supported attachment, proliferation and self-renewal of HUES1, HUES9, and iPSCs over five passages. The hPSCs cultured on PMVE-alt-MA maintained their characteristic morphology, expressed high levels of markers of pluripotency, and retained a normal karyotype. Such cost-effective, polymer-based matrices that support long-term self-renewal and proliferation of hPSCs will not only help to accelerate the translational perspectives of hPSCs, but also provide a platform to elucidate the underlying molecular mechanisms that regulate stem cell proliferation and differentiation.
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