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

Authors :
Chen-Hung Lee
Daniel Hunt
Julien George Roth
Ching-Chi Chiu
Riley A. Suhar
Bauer L. LeSavage
Alexis Jane Seymour
Chris Lindsay
Brad A. Krajina
Yi-Tung Chen
Kuo-Hsuan Chang
I-Chang Hsieh
Pao-Hsien Chu
Ming-Shien Wen
Sarah C. Heilshorn
Source :
Biomaterials. 291
Publication Year :
2022

Abstract

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.

Details

ISSN :
18785905
Volume :
291
Database :
OpenAIRE
Journal :
Biomaterials
Accession number :
edsair.doi.dedup.....0386f74b3a6e6c0be8e900ba19bb49c6