On June 18, 2024, the prestigious journal Nature Communications published the latest research work from Prof. Ran Mo’s group about immuno-protective vesicle-crosslinked hydrogel for allogenic transplantation.
The longevity of grafts remains a major challenge in allogeneic transplantation due to immune rejection. Chronic systemic immunosuppression by repeated administration of nonspecific immunosuppressants disrupts immune homeostasis, leading to increased risks of organ toxicity, myelosuppression, infections and malignancy. Cellular therapy is recognized as a promising alternative to classical immunosuppressants for achieving allograft acceptance. Mesenchymal stem cells (MSC) possessing immunomodulatory properties have been approved for treatment of graft-versus-host disease and increasingly explored for treatment of various autoimmune diseases. However, MSC have the risk of tumorigenicity due to uncontrollable self-renewal and multidirectional differentiation and the lack of persistent immunomodulatory activity resulting from limited local retention, aging and eventual death after transplant.
Professor Ran Mo’s group report a locally-immunoprotective 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), and tethered within the hydrogel by crosslinking for elevated retention at the implanted site. The MMV-Gel-established “niche” provides an immunoprotective microenvironment for the transplanted allografts by the binding of these ligands to T effector cells resulting in apoptosis of T effector cells and generation of regulatory T cells. The MMV-Gel-based immuno-protection enhances the survival and function of grafts in the mouse models of allogeneic islet and skin transplantation.
Article Link: https://www.nature.com/articles/s41467-024-49135-x
