Downstream bioprocessing of human pluripotent stem cell-derived therapeutics

• Type of Material: Article
• Authors: Sebastien Sart, Institut Pasteur, Paris; Chang Liu, Florida State University; Eric Z Zeng, Florida State University; Chunhui Xu, Emory University; Yan Li, Emory University
• Language: English
• Date: 2021-09-01
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors. Engineering in Life Sciences published by Wiley‐VCH GmbH
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/elsc.202100042
• Title of Journal or Parent Work: ENGINEERING IN LIFE SCIENCES
• Volume: 22
• Issue: 11
• Start Page: 667
• End Page: 680
• Keywords: bioprocessing; MOUSE; pluripotent stem cell; PURIFICATION; separation; SEPARATION; Science & Technology; Life Sciences & Biomedicine; DIFFERENTIATION; OLIGODENDROCYTES; ANTIBODY; PROGENITOR CELLS; CULTURE-SYSTEM; SURFACE MARKER; Biotechnology & Applied Microbiology; CARDIOMYOCYTES; downstream
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

With the advancement in lineage-specific differentiation from human pluripotent stem cells (hPSCs), downstream cell separation has now become a critical step to produce hPSC-derived products. Since differentiation procedures usually result in a heterogeneous cell population, cell separation needs to be performed either to enrich the desired cell population or remove the undesired cell population. This article summarizes recent advances in separation processes for hPSC-derived cells, including the standard separation technologies, such as magnetic-activated cell sorting, as well as the novel separation strategies, such as those based on adhesion strength and metabolic flux. Specifically, the downstream bioprocessing flow and the identification of surface markers for various cell lineages are discussed. While challenges remain for large-scale downstream bioprocessing of hPSC-derived cells, the rational quality-by-design approach should be implemented to enhance the understanding of the relationship between process and the product and to ensure the safety of the produced cells.