Immunomodulatory Functions of Human Mesenchymal Stromal Cells are Enhanced When Cultured on HEP/COL Multilayers Supplemented with Interferon-gamma

Authors

Mahsa Letter-Mahsa Haseli, University of Arkansas, FayettevilleFollow
David A. Castilla-Casadiego, University of Texas at Austin
Luis Carlos Pinzon-Herrera, University of Arkansas, FayettevilleFollow
Alexander Hillsley, University of Texas at Austin
Katherine A. Miranda-Munoz, University of Arkansas, Fayetteville
Srikanth Sivaraman, University of Arkansas, FayettevilleFollow
Adrianne M. Rosales, University of Texas at Austin
Raj R. Rao, University of Arkansas, FayettevilleFollow
Jorge Almodovar, University of Arkansas, FayettevilleFollow

Document Type

Article

Publication Date

1-2022

Keywords

Layer-by-Layer; Human mesenchymal stromal cells; Collagen; Heparin; Interferon gamma

Abstract

Human mesenchymal stromal cells (hMSCs) are multipotent cells that have been proposed for cell therapies due to their immunosuppressive capacity that can be enhanced in the presence of interferon-gamma (IFN-γ). In this study, multilayers of heparin (HEP) and collagen (COL) (HEP/COL) were used as a bioactive surface to enhance the immunomodulatory activity of hMSCs using soluble IFN-γ. Multilayers were formed, via layer-by-layer assembly, varying the final layer between COL and HEP and supplemented with IFN-γ in the culture medium. We evaluated the viability, adhesion, real-time growth, differentiation, and immunomodulatory activity of hMSCs on (HEP/COL) multilayers. HMSCs viability, adhesion, and growth were superior when cultured on (HEP/COL) multilayers compared to tissue culture plastic. We also confirmed that hMSCs osteogenic and adipogenic differentiation remained unaffected when cultured in (HEP/COL) multilayers in the presence of IFN-γ. We measured the immunomodulatory activity of hMSCs by measuring the level of indoleamine 2,3-dioxygenase (IDO) expression. IDO expression was higher on (HEP/COL) multilayers treated with IFN-gamma. Lastly, we evaluated the suppression of peripheral blood mononuclear cell (PBMC) proliferation when co-cultured with hMSCs on (HEP/ COL) multilayers with IFN-γ. hMSCs cultured in (HEP/COL) multilayers in the presence of soluble IFN-γ have a greater capacity to suppress PBMC proliferation. Altogether, (HEP/COL) multilayers with IFN-γ in culture medium provides a potent means of enhancing and sustaining immunomodulatory activity to control hMSCs immunomodulation.

Comments

This article was published with support from the Open Access Publishing Fund administered through the University of Arkansas Libraries.

Citation

Haseli, M. L., Castilla-Casadiego, D. A., Pinzon-Herrera, L. C., Hillsley, A., Miranda-Munoz, K. A., Sivaraman, S., Rosales, A. M., Rao, R. R., & Almodovar, J. (2022). Immunomodulatory Functions of Human Mesenchymal Stromal Cells are Enhanced When Cultured on HEP/COL Multilayers Supplemented with Interferon-gamma. Materials Today Bio, 13, 100194. https://doi.org/10.1016/j.mtbio.2021.100194

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This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.