Abstract
Research on human stem cells, such as pluripotent stem cells and mesenchymal stromal cells, has shown much promise in their use for regenerative medicine approaches. However, their use in patients requires large-scale expansion systems while maintaining the quality of the cells. Due to their characteristics, bioreactors have been regarded as ideal platforms to harbour stem cell biomanufacturing at a large scale. Specifically, single-use bioreactors have been recommended by regulatory agencies due to reducing the risk of product contamination, and many different systems have already been developed. This review describes single-use bioreactor platforms which have been used for human stem cell expansion and differentiation, along with their comparison with reusable systems in the development of a stem cell bioprocess for clinical applications.
Highlights
Research on human stem cells, such as pluripotent stem cells and mesenchymal stromal cells, has shown much promise in their use for regenerative medicine approaches
Human pluripotent stem cells can differentiate into any of the cell types comprising the human body. hPSCs include human embryonic stem cells, which result from the in vitro culture of cells from the inner cell mass of the blastocyst [4], and human-induced pluripotent stem cells, which are obtained by reprogramming of somatic cells [5,6]
The myriad of issues raised by the large-scale manufacturing processes of stem cells and their derivatives—such as the limited knowledge about the complexity of human stem cells; the impact of the dynamic culture environment provided by bioreactors on cell phenotype, viability, or quality; the prohibitive cost of platforms and reagents; the shift in paradigm from cells as a factory to cells as the final product, and the regulatory hurdles associated with this shift—have slowed their transition to the clinic
Summary
Despite all the advances in stem cell products for human use, regulation by agencies such as the European Medicines Agency (EMA) and the US Food and Drug Administration eering 2021, 8, x FOR PEER REVIEW (FDA) is a critical concern. Documents/eudralex, accessed on 11 April 2021) details the legislation for pharmaceutical products in the European Union, and Volume 4, in particular, details the guidelines for good manufacturing practices (GMP) for medicinal products for human and veterinary use. These GMP apply to various steps of the life of a stem cell product, from the cell bank establishment and maintenance to the manufacturing, downstream processing, fill, and finish (Figure 1). We note that the figure depicts a general stem cell product pipeline and, already at clinical scale do not perform yet differentiation in the bioreactors. Individual experiments at each scale with optimised conditions led to better results, but the exact cell density is not indicated in the article
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