Department of Chemical and Biological Engineering, State University of New York at Buffalo, Buffalo, New York 14260, USA.
Tissue Eng Part A. 2010 Feb;16(2):405-21. doi: 10.1089/ten.tea.2009.0454.
Advances in stem cell biology have afforded promising results for the generation of various cell types for therapies against devastating diseases. However, a prerequisite for realizing the therapeutic potential of stem cells is the development of bioprocesses for the production of stem cell progeny in quantities that satisfy clinical demands. Recent reports on the expansion and directed differentiation of human embryonic stem cells (hESCs) in scalable stirred-suspension bioreactors (SSBs) demonstrated that large-scale production of therapeutically useful hESC progeny is feasible with current state-of-the-art culture technologies. Stem cells have been cultured in SSBs as aggregates, in microcarrier suspension and after encapsulation. The various modes in which SSBs can be employed for the cultivation of hESCs and human induced pluripotent stem cells (hiPSCs) are described. To that end, this is the first account of hiPSC cultivation in a microcarrier stirred-suspension system. Given that cultured stem cells and their differentiated progeny are the actual products used in tissue engineering and cell therapies, the impact of bioreactor's operating conditions on stem cell self-renewal and commitment should be considered. The effects of variables specific to SSB operation on stem cell physiology are discussed. Finally, major challenges are presented which remain to be addressed before the mainstream use of SSBs for the large-scale culture of hESCs and hiPSCs.
干细胞生物学的进展为针对毁灭性疾病的各种细胞类型的治疗提供了有希望的结果。然而，实现干细胞治疗潜力的前提是开发生物工艺，以便以满足临床需求的数量生产干细胞后代。最近关于可扩展搅拌悬浮生物反应器（SSB）中人类胚胎干细胞（hESC）的扩增和定向分化的报告表明，利用当前最先进的培养技术，大规模生产治疗上有用的 hESC 后代是可行的。干细胞已在 SSB 中作为聚集体、微载体悬浮液和包封后进行培养。描述了 SSB 可用于培养 hESC 和人诱导多能干细胞（hiPSC）的各种方式。为此，这是 hiPSC 在微载体搅拌悬浮系统中培养的首次报道。鉴于培养的干细胞及其分化后代是组织工程和细胞治疗中实际使用的产品，因此应考虑生物反应器操作条件对干细胞自我更新和分化的影响。讨论了 SSB 操作特定变量对干细胞生理学的影响。最后，提出了在主流使用 SSB 大规模培养 hESC 和 hiPSC 之前仍需解决的主要挑战。
