Immuno-protective vesicle-crosslinked hydrogel for allogenic transplantation

Yuqian Wang, Renqi Huang, Yougong Lu, Mingqi Liu and Ran Mo ()
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Yuqian Wang: China Pharmaceutical University
Renqi Huang: China Pharmaceutical University
Yougong Lu: China Pharmaceutical University
Mingqi Liu: China Pharmaceutical University
Ran Mo: China Pharmaceutical University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract The longevity of grafts remains a major challenge in allogeneic transplantation due to immune rejection. Systemic immunosuppression can impair graft function and can also cause severe adverse effects. Here, we report a local immuno-protective strategy to enhance post-transplant persistence of allografts using a mesenchymal stem cell membrane-derived vesicle (MMV)-crosslinked hydrogel (MMV-Gel). MMVs are engineered to upregulate expression of Fas ligand (FasL) and programmed death ligand 1 (PD-L1). The MMVs are retained within the hydrogel by crosslinking. The immuno-protective microenvironment of the hydrogel protects allografts by presenting FasL and PD-L1. The binding of these ligands to T effector cells, the dominant contributors to graft destruction and rejection, results in apoptosis of T effector cells and generation of regulatory T cells. We demonstrate that implantation with MMV-Gel prolongs the survival and function of grafts in mouse models of allogeneic pancreatic islet cells and skin transplantation.

Date: 2024
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DOI: 10.1038/s41467-024-49135-x

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