IFN-γ-tethered hydrogels enhance mesenchymal stem cell-based immunomodulation and promote tissue repair. (November 2019)

• Record Type: Journal Article
• Authors: García, José R.; Quirós, Miguel; Han, Woojin M.; O'Leary, Monique N.; Cox, George N.; Nusrat, Asma; García, Andrés J.
• Is Part Of: Biomaterials. Volume 220(2019)
• Publication Date: 2019-11
• Subjects: Mesenchymal stem cells -- Hydrogel -- Wound repair -- Cell manufacturing; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2019.119403
• Languages: English
• ISSNs: 0142-9612

Abstract

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.