Enhanced ex vivo expansion of adult mesenchymal stem cells by fetal mesenchymal stem cell ECM
Enhanced ex vivo expansion of adult mesenchymal stem cells by fetal mesenchymal stem cell ECM
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DOI：
10.1016/j.biomaterials.2014.01.081
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发表时间：
2014-04-01
期刊：
影响因子：
14
通讯作者：
Griffith, Linda G.
中科院分区：
文献类型：
--
作者：
Ng, Chee Ping;Sharif, Abdul Rahim Mohamed;Griffith, Linda G.
高功能成人间充质干细胞（aMSC）的大规模扩增在技术上仍然具有挑战性，因为aMSC在传统的长期培养期间失去自我更新能力和多能性，并且其质量/数量随着供体年龄和疾病而下降。确定能够延长扩张和复兴的培养条件将对再生医学产生巨大影响。aMSC衍生的脱细胞化细胞外基质（ECM）已显示提供促进MSC自我更新和“干性”的微环境。由于先前的研究已经证明了人胎儿间充质干细胞（fMSCs）的上级增殖和成骨潜力，我们假设他们的ECM可能会促进临床相关的aMSCs的扩增。我们证明了aMSC在fMSC衍生的ECM上比aMSC衍生的ECM和传统的组织培养器（TCPS）更具增殖性（类似于1.6倍）。这些aMSC更小且尺寸更均匀（中值+/-四分位数范围：15.5 +/- 4.1 μ m，aMSC ECM和TCPS分别为17.2 +/- 5.0 μ m和15.5 - 4.1 μ m），表现出必要的生物标志物特征，并且成骨、成脂和成软骨表达染色阳性;表明它们在培养期间保持多能性。此外，与TCPS相比，fMSC ECM改善了晚期传代的aMSC的增殖（类似于2.2倍）、大小（19.6 +/- 11.9 μ m vs 30.2 +/- 14.5 μ m）和分化潜力。总之，我们已经建立了fMSC ECM作为一个有前途的细胞培养平台，用于体外扩增的aMSC。(c)2014作者由爱思唯尔有限公司出版。保留所有权利。
Large-scale expansion of highly functional adult human mesenchymal stem cells (aMSCs) remains technologically challenging as aMSCs lose self renewal capacity and multipotency during traditional long-term culture and their quality/quantity declines with donor age and disease. Identification of culture conditions enabling prolonged expansion and rejuvenation would have dramatic impact in regenerative medicine. aMSC-derived decellularized extracellular matrix (ECM) has been shown to provide such microenvironment which promotes MSC self renewal and "stemness". Since previous studies have demonstrated superior proliferation and osteogenic potential of human fetal MSCs (fMSCs), we hypothesize that their ECM may promote expansion of clinically relevant aMSCs. We demonstrated that aMSCs were more proliferative (similar to 1.6 x) on fMSC-derived ECM than aMSC-derived ECMs and traditional tissue culture wares (TCPS). These aMSCs were smaller and more uniform in size (median +/- interquartile range: 15.5 +/- 4.1 mu m versus 17.2 +/- 5.0 pm and 15.5 4.1 mu m for aMSC ECM and TCPS respectively), exhibited the necessary biomarker signatures, and stained positive for osteogenic, adipogenic and chondrogenic expressions; indications that they maintained multipotency during culture. Furthermore, fMSC ECM improved the proliferation (similar to 2.2 x), size (19.6 +/- 11.9 mu m vs 30.2 +/- 14.5 mu m) and differentiation potential in late-passaged aMSCs compared to TCPS. In conclusion, we have established fMSC ECM as a promising cell culture platform for ex vivo expansion of aMSCs. (c) 2014 The Authors. Published by Elsevier Ltd. All rights reserved.