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


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-? 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-? that activates encapsulated hMSCs to increase their immunomodulatory functions and avoids the need for ex vivo manipulation. Tethering IFN-? to the hydrogel increases retention of IFN-? within the biomaterial while preserving its biological activity. hMSCs encapsulated within hydrogels with tethered IFN-? 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-? and untreated hMSCs. Importantly, hMSCs encapsulated within hydrogels with tethered IFN-? accelerated healing of colonic mucosal wounds in both immunocompromised and immunocompetent mice. This novel approach for licensing hMSCs with IFN-? may enhance the clinical translation and efficacy of hMSC-based therapies.

SUBMITTER: Garcia JR 

PROVIDER: S-EPMC6717550 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

García José R JR   Quirós Miguel M   Han Woojin M WM   O'Leary Monique N MN   Cox George N GN   Nusrat Asma A   García Andrés J AJ  

Biomaterials 20190802


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 reco  ...[more]

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