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人骨髓间充质干细胞在基于肝素的水凝胶上的培养和通过凝胶弹性和肝素量调节相互作用。

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

机构信息

School of Materials Science and Engineering, Department of Nanobio Materials and Electronics, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.

出版信息

Acta Biomater. 2013 Aug;9(8):7833-44. doi: 10.1016/j.actbio.2013.04.041. Epub 2013 May 2.

DOI:10.1016/j.actbio.2013.04.041
PMID:23643605
Abstract

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 β1 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.

摘要

人脂肪来源干细胞(hADSCs)是组织工程和再生医学中一种很有前途的细胞来源,不存在种族问题,且易于大量获取。传统的 hADSC 培养表面,如组织培养板(TCPs),不能提供最佳的环境线索,导致干细胞的扩增有限、多能性丧失和不理想的分化。本研究表明,未经额外修饰的基于肝素的水凝胶为 hADSC 的黏附和增殖提供了极好的表面,其可以通过肝素的量(正向)和水凝胶的弹性(负向)进一步进行调节。优化后的基于肝素的水凝胶可以选择性地调节 hADSCs 和人骨髓间充质干细胞(但不是所有细胞)的黏附,与 TCP 相比,细胞增殖显著增加。此外,在维持多能性和特定分化方面,基于肝素的水凝胶比 TCP 优越得多。人间充质干细胞在基于肝素的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,并且这些优越的特性在培养基中存在血清蛋白的情况下仍然存在。因此,基于肝素的水凝胶可以成为各种应用中培养间充质干细胞的有力平台。

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