Abstract
Cell-based therapy (CBT) is attracting much attention to treat incurable diseases. In recent years, several clinical trials have been conducted using human pluripotent stem cells (hPSCs), and other potential therapeutic cells. Various private- and government-funded organizations are investing in finding permanent cures for diseases that are difficult or expensive to treat over a lifespan, such as age-related macular degeneration, Parkinson’s disease, or diabetes, etc. Clinical-grade cell manufacturing requiring current good manufacturing practices (cGMP) has therefore become an important issue to make safe and effective CBT products. Current cell production practices are adopted from conventional antibody or protein production in the pharmaceutical industry, wherein cells are used as a vector to produce the desired products. With CBT, however, the “cells are the final products” and sensitive to physico- chemical parameters and storage conditions anywhere between isolation and patient administration. In addition, the manufacturing of cellular products involves multi-stage processing, including cell isolation, genetic modification, PSC derivation, expansion, differentiation, purification, characterization, cryopreservation, etc. Posing a high risk of product contamination, these can be time- and cost- prohibitive due to maintenance of cGMP. The growing demand of CBT needs integrated manufacturing systems that can provide a more simple and cost-effective platform. Here, we discuss the current methods and limitations of CBT, based upon experience with biologics production. We review current cell manufacturing integration, automation and provide an overview of some important considerations and best cGMP practices. Finally, we propose how multi-stage cell processing can be integrated into a single bioreactor, in order to develop streamlined cGMP-compliant cell processing systems.
Highlights
Human pluripotent stem cells, including embryonic stem cells (ESCs) (Thomson et al, 1998) and induced pluripotent stem cells (Takahashi et al, 2007) are attractive tools in the field of regenerative medicine because of their ability to self-renew and differentiate into any cell type in the human body
HiPSCs are a better source for autologous Cell-based therapy (CBT), they are less preferable for clinical trials because they are less genetically stable than hESCs (Attwood and Edel, 2019)
The bioreactor platform is widely used for the large-scale expansion of Human pluripotent stem cells (hPSCs)-based CBT production because it is easy to operate and different physicochemical parameters can be regulated in a closed-system
Summary
Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) (Thomson et al, 1998) and induced pluripotent stem cells (iPSCs) (Takahashi et al, 2007) are attractive tools in the field of regenerative medicine because of their ability to self-renew and differentiate into any cell type in the human body. We will discuss how genetic modification- transfection or transduction, reprogramming, differentiation, purification and development of final products in a single bioreactor can be integrated. Cell processing differs widely from pharmaceutical proteins or vaccine production current manufacturing practices are based on conventional biologics manufacturing that may not be compatible for CBT (Bennett, 2018; Sterlling, 2018).
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