Delivery of Immobilized IFN-γ With PCN-333 and Its Effect on Human Mesenchymal Stem Cells

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IFN manuscript (Revised and clean) TOC Delivery of Immobilized IFN.pdf (2.41 MB)

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https://pubs.acs.org/doi/10.1021/acsbiomaterials.2c01038

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https://doi.org/10.1021/acsbiomaterials.2c01038
 http://hdl.handle.net/11603/32606

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UMBC Chemical, Biochemical & Environmental Engineering Department

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Author/Creator ORCID

https://orcid.org/0000-0002-1151-3878

Date

2023-01-04

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journal articles
postprints
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Citation of Original Publication

Phipps, Josh, Mahsa Haseli, Luis Pinzon-Herrera, Ben Wilson, Joshua Corbitt, Shannon Servoss, and Jorge Almodovar. “Delivery of Immobilized IFN-γ With PCN-333 and Its Effect on Human Mesenchymal Stem Cells.” ACS Biomaterials Science & Engineering 9, no. 2 (February 13, 2023): 671–79. https://doi.org/10.1021/acsbiomaterials.2c01038.

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This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Biomaterials Science & Engineering, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsbiomaterials.2c01038.

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Abstract

Interferon-gamma (IFN-γ) plays a vital role in modulating the immunosuppressive properties of human mesenchymal stem/stromal cells (hMSCs) used in cell therapies. However, IFN-γ suffers from low bioavailability and degrades in media, creating a challenge when using IFN-γ during the manufacturing of hMSCs. Metal–organic frameworks (MOFs), with their porous interiors, biocompatibility, high loading capacity, and ability to be functionalized for targeting, have become an increasingly suitable platform for protein delivery. In this work, we synthesize the MOF PCN-333(Fe) and show that it can be utilized to immobilize and deliver IFN-γ to the local extracellular environment of hMSCs. In doing so, the cells proliferate and differentiate appropriately with no observed side effects. We demonstrate that PCN-333(Fe) MOFs containing IFN-γ are not cytotoxic to hMSCs, can promote the expression of proteins that play a role in immune response, and are capable of inducing indoleamine 2,3-dioxygenase (IDO) production similar to that of soluble IFN-γ at lower concentrations. Overall, using MOFs to deliver IFN-γ may be leveraged in the future in the manufacturing of therapeutically relevant hMSCs.