Abstract
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.
Highlights
The advancement of induced pluripotent stem cells (iPSCs)-based personalized cell therapies is currently hindered by the high cost to biomanufacture the cells[1,2,3,4,5]
H9 hESCs were purchased from WiCell Research Institute. human pluripotent stem cells (hPSCs) were maintained in 6-welll plate coated with Matrigel (BD Biosciences) in Essential 8TM medium (E8, Invitrogen)[7]
They formed compact colonies when cultured on Matrigel-coated cell culture plates in the chemical defined Essential 8 (E8) medium. iPSCs expressed the pluripotency makers, OCT4 and NANOG
Summary
The advancement of iPSC-based personalized cell therapies is currently hindered by the high cost to biomanufacture the cells[1,2,3,4,5]. Patient cells are sent to the center, and the produced cells are sent back to the point-of-care for transplantation This centralized biomanufacturing has additional disadvantages[1,42,45], including: (i) patient cells may be cross-contaminated and (ii) there are high costs and risks associated with the transportation, logistics, tracking, and recording. One method to significantly reduce the biomanufacturing cost is to make cells in individualized, closed, computer controlled miniature cell culture device at the point-of-care (i.e. the cGMP-in-a-box production)[42]. Miniaturizing the culture system makes it possible to simultaneously biomanufacture cells for large numbers of patients at the point-of-care (i.e. high throughput biomanufacturing). With the assist of this hydrogel scaffold, integrated the bioprocessing including the iPSC expansion, iPSC differentiation into NSCs, the subsequent depletion of undifferentiated iPSCs from the product, and concentrating and transporting the produced cells to the surgery room into two closed, 15 ml conical tubes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
