Tuning pro-survival effects of human induced pluripotent stem cell-derived exosomes using elastin-like polypeptides
Summary
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 Dec;291:121864 |
| PubMed | 36343608 |
| DOI | 10.1016/j.biomaterials.2022.121864 |