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 (IFNγ). 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 IFNγ. Multilayers were formed, via layer-by-layer assembly, varying the final layer between COL and HEP and supplemented with IFNγ in the culture medium. This study evaluates the viability, adhesion, real-time growth, differentiation, and immunomodulatory activity of hMSCs on HEP/COL surfaces. HMSCs viability, adhesion, and growth were superior when cultured on HEP/COL surfaces compared to tissue culture plastic. The possibility of inducing hMSCs to differentiate into osteoblasts and adipocytes was measured by exposing them to differentiation medium specific to each lineage after IFNγ treatment. This study confirms that hMSC osteogenic and adipogenic differentiation remained unaffected when cultured in HEP/COL multilayers. This study measures the level of indoleamine 2,3-dioxygenase (IDO) secretion to evaluate the hMSCs immunomodulatory factor expression. IDO expression was higher on HEP/COL surfaces treated with IFNγ. This study investigates the suppression of T-cell proliferation in peripheral blood mononuclear cells (PBMC) when co-cultured with hMSCs on HEP/COL multilayers with IFNγ. hMSCs cultured in HEP/COL surfaces in the presence of soluble IFNγ have a greater capacity to suppress T-cell proliferation from CD3/CD28-activated peripheral blood mononuclear cells. Altogether, (HEP/COL) multilayers with IFNγ in culture medium provides a potent means of enhancing and sustaining immunomodulatory activity to control hMSCs immunomodulation leading to a potential improvement in the efficacy of hMSCs-based therapies aimed at treating inflammatory and immune diseases.

Effect of heparin/collagen layer-by-layer coating in immunomodulatory functions of mesenchymal stromal/stem cells stimulated by IFN-γ

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.