Human mesenchymal stem cell culture on heparin-based hydrogels and the modulation of interactions by gel elasticity and heparin amount

Human mesenchymal stem cell culture on heparin-based hydrogels and the modulation of interactions by gel elasticity and heparin amount
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DOI:
10.1016/j.actbio.2013.04.041
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发表时间:
2013-08-01
期刊:
影响因子:
9.7
通讯作者:
Tae, Giyoong
Tae, Giyoong
中科院分区:
工程技术1区
文献类型:
--
作者:
Kim, Mihye;Kim, Young Ha;Tae, Giyoong

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人脂肪来源干细胞(HADSCs)是组织工程和再生医学的一种很有前途的细胞来源,不存在伦理学问题,易于大量获取。传统的hADSC培养表面,如组织培养板(TCP),不能提供最佳的环境信号,导致干细胞有限的扩增、多能性的丧失和不希望的分化。本研究表明,肝素基水凝胶在没有额外修饰的情况下为hADSCs的黏附和增殖提供了良好的表面,这一表面进一步可以通过肝素的量(正的方式)和水凝胶的弹性(负的方式)来调节。优化后的肝素水凝胶可以选择性地调节hADSCs与人骨髓干细胞(但不是所有细胞)的黏附,并导致细胞增殖明显高于磷酸三钙。此外,在维持多能性和特异性分化方面,肝素水凝胶明显优于磷酸三钙。人骨髓间充质干细胞在肝素水凝胶上的选择性结合和增殖在很大程度上是由整合素β1和选择素介导的,而且这些优越的特性与培养液中的血清蛋白无关。因此,基于肝素的水凝胶在各种应用中可能成为培养间充质干细胞的强大平台。(C)2013 Acta Materialia Inc.由Elsevier Ltd.出版。保留所有权利。
Human adipose-derived stem cells (hADSCs) are a promising cell source for tissue engineering and regenerative medicine with no ethnical issue and easy access of large quantities. Conventional surfaces for hADSC culture, such as tissue culture plates (TCPs), do not provide optimal environmental cues, leading to limited expansion, loss of pluripotency and undesirable differentiation of stem cells. The present study demonstrated that heparin-based hydrogels without additional modification provided an excellent surface for adhesion and proliferation of hADSCs, which were further tunable by both the amount of heparin (in a positive way) and the elasticity of hydrogel (in a negative way). The optimized heparin-based hydrogel could selectively modulate the adhesion of hADSCs and human bone marrow stem cells (but not all kinds of cells), and resulted in a significant increase in cell proliferation compared to TCP. Furthermore, in terms of the maintenance of pluripotency and specific differentiation, heparin-based hydrogel was much superior to TCP. The selective binding and proliferation of human mesenchymal stem cells on heparin-based hydrogel over other hydrogels were largely mediated by integrin beta 1 and selectin, and these superior characteristics were observed regardless of the presence of serum proteins in the culture medium. Consequently, heparin-based hydrogel could be a powerful platform for cultivation of mesenchymal stem cells in various applications. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.