Use of polyvinyl alcohol for chimeric antigen receptor T-cell expansion
Use of polyvinyl alcohol for chimeric antigen receptor T-cell expansion
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DOI：
10.1016/j.exphem.2019.11.007
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发表时间：
2019-12-01
影响因子：
2.6
通讯作者：
Wilkinson, Adam C.
中科院分区：
文献类型：
--
作者：
Nishimura, Toshinobu;Hsu, Ian;Wilkinson, Adam C.
血清白蛋白长期以来一直是体外造血和免疫细胞培养的必需补充剂。然而，血清白蛋白培养基补充剂代表细胞培养物中生物污染的主要来源，并且通常导致细胞功能丧失。由于血清白蛋白具有显著的批次间变异性，因此也被认为是导致实验重现性出现重大问题的原因。我们最近发现合成聚合物聚乙烯醇（PVA）作为一种廉价的，良好的生产规范兼容的，生物惰性的血清白蛋白替代体外造血干细胞培养。重要的是，PVA不含困扰血清白蛋白培养基的生物污染物。在这里，我们描述了PVA可以在一系列血液和免疫细胞培养物中取代血清白蛋白，包括细胞系、原发性白血病样本和人T淋巴细胞。PVA甚至可以在功能性嵌合抗原受体（CAR）T细胞的产生和扩增中取代人血清，为这种临床细胞治疗提供了一种潜在的更安全和更具成本效益的方法。总之，PVA代表了血液学和免疫学中一系列细胞培养物中血清白蛋白的化学定义、生物惰性和廉价替代品。(C)2019 ISEH -血液学和干细胞学会。爱思唯尔公司出版
Serum albumin has long been an essential supplement for ex vivo hematopoietic and immune cell cultures. However, serum albumin medium supplements represent a major source of biological contamination in cell cultures and often cause loss of cellular function. As serum albumin exhibits significant batch-to-batch variability, it has also been blamed for causing major issues in experimental reproducibility. We recently discovered the synthetic polymer polyvinyl alcohol (PVA) as an inexpensive, Good Manufacturing Practice-compatible, and biologically inert serum albumin replacement for ex vivo hematopoietic stem cell cultures. Importantly, PVA is free of the biological contaminants that have plagued serum albumin-based media. Here, we describe that PVA can replace serum albumin in a range of blood and immune cell cultures including cell lines, primary leukemia samples, and human T lymphocytes. PVA can even replace human serum in the generation and expansion of functional chimeric antigen receptor (CAR) T cells, offering a potentially safer and more cost-efficient approach for this clinical cell therapy. In summary, PVA represents a chemically defined, biologically inert, and inexpensive alternative to serum albumin for a range of cell cultures in hematology and immunology. (C) 2019 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.