4.8 Article

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

期刊

BIOMATERIALS
卷 291, 期 -, 页码 -

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121864

关键词

Elastin-like polypeptides; Human induced pluripotent stem cells; Exosomes; Biomaterials; Recombinant protein; Cell culture coating; Extracellular matrix

资金

  1. National Science Council of Taiwan [MOST 109-2314-B-182A-035-MY3, MOST 108-2221-E-182A-002]
  2. Chang Gung Memorial Hospital [CMRPG3J1281, CMRPG3K1332, CMRPG3L1301, CORPG3M0151, CMRPG3M1461]
  3. National Science Foundation [DMR-1808415]
  4. National Institutes of Health (NIH) [R21 HL138042, R01 HL14271, R01 EB027171]
  5. Stanford Lieberman Fellowship
  6. NSF Graduate Research Fellowship
  7. Smith Family Stanford Graduate Fellowship
  8. Stanford Bio-X Bowes Graduate Fellowship program
  9. NIH Training Grant in Biotechnology [T32-GM008412]
  10. Center for Big Data Analytics and Statistics at Chang Gung Memorial Hospital [CLRPG3D0049]

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This study evaluates the potency of exosomes secreted by human induced pluripotent stem cells (iPSCs) using designer biomaterial substrates. The results show that iPSCs grown on RDG-ELP substrates produce exosomes with similar pro-survival effects to those grown on Matrigel, while using RGD-ELP substrates leads to significantly reduced exosome potency.
Exosome-based regenerative therapies are potentially easier to manufacture and safer to apply compared to cellbased 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 animalfree 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.

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