Immuno-protective vesicle-crosslinked hydrogel for allogenic transplantation.
Nat Commun
; 15(1): 5176, 2024 Jun 18.
Article
em En
| MEDLINE
| ID: mdl-38890279
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tratamento
Base de dados:
MEDLINE
Assunto principal:
Transplante Homólogo
/
Transplante das Ilhotas Pancreáticas
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Transplante de Pele
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Linfócitos T Reguladores
/
Hidrogéis
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Proteína Ligante Fas
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Camundongos Endogâmicos C57BL
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2024
Tipo de documento:
Article