Gao Tingting, Zhao Xiyuan, Hao Jie, Tian Yao, Ma Huike, Liu Wenjing, An Bin, Sun Faguo, Liu Shasha, Guo Baojie, Niu Shuaishuai, Li Zhongwen, Wang Chenxin, Wang Yukai, Feng Guihai, Wang Liu, Li Wei, Wu Jun, Guo Meijin, Zhou Qi, Gu Qi
State Key Laboratory of Stem Cell and Reproductive Biology, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Mater Today Bio. 2023 May 5;20:100662. doi: 10.1016/j.mtbio.2023.100662. eCollection 2023 Jun.
Mesenchymal stromal cells (MSCs) derived from human embryonic stem cells (hESCs) are a desirable cell source for cell therapy owing to their capacity to be produced stably and homogeneously in large quantities. However, a scalable culture system for hPSC-derived MSCs is urgently needed to meet the cell quantity and quality requirements of practical clinical applications. In this study, we developed a new microcarrier with hyaluronic acid (HA) as the core material, which allowed scalable serum-free suspension culture of hESC-derived MSCs (IMRCs). We used optimal microcarriers with a coating collagen concentration of 100 μg/mL or concave-structured surface (cHAMCs) for IMRC amplification in a stirred bioreactor, expanding IMRCs within six days with the highest yield of over one million cells per milliliter. In addition, the harvested cells exhibited high viability, immunomodulatory and regenerative therapeutic promise comparable to monolayer cultured MSCs while showing more increased secretion of extracellular matrix (ECM), particularly collagen-related proteins. In summary, we have established a scalable culture system for hESC-MSCs, providing novel approaches for future cell therapies.
源自人类胚胎干细胞（hESCs）的间充质基质细胞（MSCs）是细胞治疗中理想的细胞来源，因为它们能够稳定且大量地均匀产生。然而，迫切需要一种可扩展的培养系统来培养源自人多能干细胞（hPSC）的MSCs，以满足实际临床应用对细胞数量和质量的要求。在本研究中，我们开发了一种以透明质酸（HA）为核心材料的新型微载体，它能够实现源自hESC的MSCs（IMRCs）的可扩展无血清悬浮培养。我们使用包被胶原蛋白浓度为100μg/mL的最佳微载体或凹面结构表面的微载体（cHAMCs）在搅拌式生物反应器中扩增IMRCs，在六天内使IMRCs扩增，每毫升产量最高超过一百万个细胞。此外，收获的细胞具有高活力，免疫调节和再生治疗潜力与单层培养的MSCs相当，同时显示出更多细胞外基质（ECM）的分泌增加，特别是与胶原蛋白相关的蛋白质。总之，我们建立了一种用于hESC-MSCs的可扩展培养系统，为未来的细胞治疗提供了新方法。
