Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, Nebraska, USA.
Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Sci Rep. 2017 Jan 6;7:40191. doi: 10.1038/srep40191.
Human induced pluripotent stem cells (iPSCs) are ideal cell sources for personalized cell therapies since they can be expanded to generate large numbers of cells and differentiated into presumably all the cell types of the human body in vitro. In addition, patient specific iPSC-derived cells induce minimal or no immune response in vivo. However, with current cell culture technologies and bioprocessing, the cost for biomanufacturing clinical-grade patient specific iPSCs and their derivatives are very high and not affordable for majority of patients. In this paper, we explored the use of closed and miniature cell culture device for biomanufacturing patient specific neural stem cells (NSCs) from iPSCs. We demonstrated that, with the assist of a thermoreversible hydrogel scaffold, the bioprocessing including iPSC expansion, iPSC differentiation into NSCs, the subsequent depletion of undifferentiated iPSCs from the NSCs, and concentrating and transporting the purified NSCs to the surgery room, could be integrated and completed within two closed 15 ml conical tubes.
人类诱导多能干细胞（iPSCs）是个性化细胞治疗的理想细胞来源，因为它们可以被扩增以产生大量细胞，并在体外分化为人体的所有细胞类型。此外，患者特异性 iPSC 衍生细胞在体内引起的免疫反应最小或没有。然而，目前的细胞培养技术和生物加工技术，生物制造临床级别的患者特异性 iPSCs 及其衍生物的成本非常高，大多数患者无法负担得起。在本文中，我们探索了使用封闭和微型细胞培养装置来生物制造患者特异性神经干细胞（NSCs）从 iPSCs。我们证明，在热可逆水凝胶支架的辅助下，生物加工过程包括 iPSC 扩增、iPSC 分化为 NSCs、随后从 NSCs 中去除未分化的 iPSC，以及将纯化的 NSCs 浓缩并输送到手术室，都可以集成并在两个封闭的 15ml 锥形管内完成。
