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Discovery of a Novel Polymer for Xeno‐Free, Long‐Term Culture of Human Pluripotent Stem Cell Expansion
Author(s) -
Nasir Aishah,
Thorpe Jordan,
Burroughs Laurence,
Meurs Joris,
PijuanGalito Sara,
Irvine Derek J.,
Alexander Morgan R.,
Denning Chris
Publication year - 2021
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202001448
Subject(s) - induced pluripotent stem cell , cell culture , nanotechnology , chemistry , biomedical engineering , materials science , microbiology and biotechnology , biology , embryonic stem cell , biochemistry , medicine , genetics , gene
Human pluripotent stem cells (hPSCs) can be expanded and differentiated in vitro into almost any adult tissue cell type, and thus have great potential as a source for cell therapies with biomedical application. In this study, a fully‐defined polymer synthetic substrate is identified for hPSC culture in completely defined, xenogenic (xeno)‐free conditions. This system can overcome the cost, scalability, and reproducibility limitations of current hPSC culture strategies, and facilitate large‐scale production. A high‐throughput, multi‐generational polymer microarray platform approach is used to test over 600 unique polymers and rapidly assess hPSC‐polymer interactions in combination with the fully defined xeno‐free medium, Essential 8 (E8). This study identifies a novel nanoscale phase separated blend of poly(tricyclodecane‐dimethanol diacrylate) and poly(butyl acrylate) (2:1 v/v), which supports long‐term expansion of hPSCs and can be readily coated onto standard cultureware. Analysis of cell‐polymer interface interactions through mass spectrometry and integrin blocking studies provides novel mechanistic insight into the role of the E8 proteins in promoting integrin‐mediated hPSC attachment and maintaining hPSC signaling, including ability to undergo multi‐lineage differentiation. This study therefore identifies a novel substrate for long‐term serial passaging of hPSCs in serum‐free, commercial chemically‐defined E8, which provides a promising and economic hPSC expansion platform for clinical‐scale application.