期刊
BIOCHEMICAL ENGINEERING JOURNAL
卷 108, 期 -, 页码 3-13出版社
ELSEVIER
DOI: 10.1016/j.bej.2015.08.014
关键词
Mesenchymal stem/stromalcells; Bioreactors; Microcarriers; Cell culture media; Separation; Scale-up
The long-term outlook for regenerative medicine predicts an increased need for scalable cell expansion technologies that utilize non-animal derived materials and are compatible with the limited number of downstream processing steps required for cell-based therapies. As more stem cell therapeutics progress through clinical testing, current in vitro culture methods using planar vessels are proving cumbersome to scale. Therefore, alternative processes are under investigation. Many human mesenchymal stem/stromal cell (hMSC) bioreactor-based manufacturing processes, in particular, are complicated by the requirement to separate cells from microcarriers with high cell yield and viability whilst maintaining target phenotypic and functional characteristics. Here we review currently available technologies and ongoing development for the expansion of cellular therapeutics, with focus on allogeneic hMSCs and microcarrier-based processes. Upstream challenges include the interplay between the cell culture substrate and media formulation, sourcing of high quality animal-free reagents, and considerations for the use of microcarriers in stirred-tank systems. Complications in downstream processes include harvest approaches for separation of cells from microcarriers and volume reduction. (C) 2015 The Authors. Published by Elsevier B.V.
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