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Biomaterials. 2019 Nov;220:119403. doi: 10.1016/j.biomaterials.2019.119403. Epub 2019 Aug 2.

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

Author information

1
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.
2
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
3
Bolder BioTechnology, Inc., Boulder, CO, USA.
4
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA. Electronic address: andres.garcia@me.gatech.edu.

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.

KEYWORDS:

Cell manufacturing; Hydrogel; Mesenchymal stem cells; Wound repair

PMID:
31401468
PMCID:
PMC6717550
[Available on 2020-11-01]
DOI:
10.1016/j.biomaterials.2019.119403

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