IFN-γ-tethered hydrogels enhance mesenchymal stem cell-based immunomodulation and promote tissue repair

José R. García, Miguel Quirós, Woojin M. Han, Monique N. O'Leary, George N. Cox, Asma Nusrat, Andrés J. García

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Because of their immunomodulatory activities, human mesenchymal stem cells (hMSCs) are being explored to treat a variety of chronic conditions such as inflammatory bowel disorders and graft-vs-host disease. Treating hMSCs with IFN-γ prior to administration augments these immunomodulatory properties; however, this ex vivo treatment limits the broad applicability of this therapy due to technical and regulatory issues. In this study, we engineered an injectable synthetic hydrogel with tethered recombinant IFN-γ that activates encapsulated hMSCs to increase their immunomodulatory functions and avoids the need for ex vivo manipulation. Tethering IFN-γ to the hydrogel increases retention of IFN-γ within the biomaterial while preserving its biological activity. hMSCs encapsulated within hydrogels with tethered IFN-γ exhibited significant differences in cytokine secretion and showed a potent ability to halt activated T-cell proliferation and monocyte-derived dendritic cell differentiation compared to hMSCs that were pre-treated with IFN-γ and untreated hMSCs. Importantly, hMSCs encapsulated within hydrogels with tethered IFN-γ accelerated healing of colonic mucosal wounds in both immunocompromised and immunocompetent mice. This novel approach for licensing hMSCs with IFN-γ may enhance the clinical translation and efficacy of hMSC-based therapies.

Original languageEnglish
Article number119403
JournalBiomaterials
Volume220
DOIs
StatePublished - Nov 2019
Externally publishedYes

Keywords

  • Cell manufacturing
  • Hydrogel
  • Mesenchymal stem cells
  • Wound repair

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