Tuning pro-survival effects of human induced pluripotent stem cell-derived exosomes using elastin-like polypeptides


Exosome-based regenerative therapies are potentially easier to manufacture and safer to apply compared to cell-based therapies. However, many questions remain about how to bio-manufacture reproducible and potent exosomes using animal-free reagents. Here we evaluate the hypothesis that designer biomaterial substrates can be used to alter the potency of exosomes secreted by human induced pluripotent stem cells (iPSCs). Two animal-free designer matrices were fabricated based on recombinant elastin-like polypeptides (ELPs): one including a cell-adhesive RGD ligand and a second with a non-adhesive RDG peptide. While iPSCs cultured on these two substrates and Matrigel-coated controls had similar levels of proliferation, the RDG-ELP substrate significantly increased protein expression of stemness markers OCT4 and SOX2 and suppressed spontaneous differentiation compared to those on RGD-ELP. The pro-survival potency of iPSC-derived exosomes was evaluated using three distinct stress tests: serum starvation in murine fibroblasts, hypoxia in human endothelial cells, and hyperosmolarity in canine kidney cells. In all three cases, exosomes produced by iPSCs grown on RDG-ELP substrates had similar pro-survival effects to those produced using iPSCs grown on Matrigel, while use of RGD-ELP substrates led to significantly reduced exosome potency. These data demonstrate that recombinant substrates can be designed for the robust bio-manufacturing of iPSC-derived, pro-survival exosomes. Copyright © 2022 Elsevier Ltd. All rights reserved.

Authors Lee CH, Hunt D, Roth JG, Chiu CC, Suhar RA, LeSavage BL, Seymour AJ, Lindsay C, Krajina BA, Chen YT, Chang KH, Hsieh IC, Chu PH, Wen MS, Heilshorn SC
Journal Biomaterials
Publication Date 2022 Oct 26;291:121864
PubMed 36343608
DOI 10.1016/j.biomaterials.2022.121864

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