Expansion of Human Mesenchymal Stem Cells Using Microcarriers and Human Platelet Lysate
semanticscholar(2014)
摘要
level: intermediate C ell therapy holds the promise of delivering the next generation of future medical breakthroughs. In this respect, multipotent progenitor cells such as human mesenchymal stem cells (hMSCs) have attracted high clinical interest because of their ability to differentiate into various cell types and their immunoregulatory properties. Furthermore, hMSCs express only low levels of class I major histocompatibility complex (MHC I) molecules on their surfaces and are therefore invisible to a host’s immune system. Finally, hMSCs can actively suppress the innate immune system by expressing a number of secreted factors such as factor H and human leukocyte antigen G5 (HLA-G5). Together, those features enable the allogeneic use of hMSCs and thus make them an attractive target for commercial therapeutic development. Allogeneic therapies have the advantage over autologous therapies of the potential for centralized manufacturing, storage, and distribution similar to classical therapeutic agents such as small molecules and biologics. In addition, allogeneic cell therapies can be produced at large scales, which will be imperative to ensure commercial viability. Currently, large-scale expansion of hMSCs is mostly performed using traditional f latbed cultures (e.g., in f lasks) and multilayer vessels such as 10-layer and 40-layer stacked trays, enabling lot sizes of 10–50 billion cells (1). Although such lot sizes are sufficient to satisfy the needs of clinical development, it is widely believed that multilayer vessels will not constitute a cost-effective approach for marketed products. Thus, significant efforts are under way to develop alternatives to f latbed cultures. One promising approach is the expansion of hMSCs on microcarriers in stirred-tank bioreactors (2–4). This technology will allow for development of scaled-up processes in which expansion can go from small-scale vessels (e.g., 3 L) to large vessels (e.g., 1,000 L). Although such processes are still in development, it can be estimated that a single 1,000-L bioreactor could provide enough cells to produce thousands of clinical hMSC doses. Thus, microcarrierbased expansion of hMSCs offers an attractive process for allogeneic cell therapy products. In addition to the choice of platform technology, the composition of a cell culture medium used for hMSCs is of significant concern for development of allogeneic cell therapy products. To date, nearly all such products in clinical trials require added serum in their growth media for expansion, most prominently fetal bovine serum (FBS). But that poses an important risk because current good manufacturing practice (CGMP)–quality FBS is of limited Immunocytochemical staining shows cultured human bone marrow–derived mesenchymal stem cells stained with STRO-1 and CD90 antibodies. Nuclei of the cells are visualized using DAPI (blue).
更多查看译文
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要