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Immuno-protective vesicle-crosslinked hydrogel for allogenic transplantation

Author

Listed:
  • 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)

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.

Suggested Citation

  • Yuqian Wang & Renqi Huang & Yougong Lu & Mingqi Liu & Ran Mo, 2024. "Immuno-protective vesicle-crosslinked hydrogel for allogenic transplantation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49135-x
    DOI: 10.1038/s41467-024-49135-x
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    1. Eiji Yoshihara & Carolyn O’Connor & Emanuel Gasser & Zong Wei & Tae Gyu Oh & Tiffany W. Tseng & Dan Wang & Fritz Cayabyab & Yang Dai & Ruth T. Yu & Christopher Liddle & Annette R. Atkins & Michael Dow, 2020. "Immune-evasive human islet-like organoids ameliorate diabetes," Nature, Nature, vol. 586(7830), pages 606-611, October.
    2. Jeremy J. McGuire & Jeremy S. Frieling & Chen Hao Lo & Tao Li & Ayaz Muhammad & Harshani R. Lawrence & Nicholas J. Lawrence & Leah M. Cook & Conor C. Lynch, 2021. "Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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