Exopolysaccharide-Treated Dendritic Cells Effectively Ameliorate Acute Graft-versus-Host Disease.
Transplant Cell Ther
; 30(1): 79.e1-79.e10, 2024 Jan.
Article
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| MEDLINE
| ID: mdl-37924979
ABSTRACT
Graft-versus-host disease (GVHD) is a primary and often lethal complication of allogenic hematopoietic stem cell transplantation (HSCT). Prophylactic regimens for GVHD are given as standard pretransplantation therapy; however, up to 50% of these patients develop acute GVHD (aGVHD) and require additional immunosuppressive intervention. Using a mouse GVHD model, we previously showed that injecting mice with exopolysaccharide (EPS) from Bacillus subtilis prior to GVHD induction significantly increased 80-day survival after transplantation of complete allogeneic major histocompatibility complex-mismatched cells. To ask whether EPS might also inhibit GVHD in humans, we used humanized NSG-HLA-A2 mice and induced GVHD by i.v. injection of A2neg human peripheral blood mononuclear cells (PBMCs). Because we could not inject human donors with EPS, we transferred EPS-pretreated dendritic cells (DCs) to inhibit aGVHD. We derived these DCs from CD34+ human cord blood cells, treated them with EPS, and then injected them together with PBMCs into the NSG-HLA-A2 mice. We found that all mice that received untreated DCs were dead by day 35, whereas 25% of mice receiving EPS-treated DCs (EPS-DCs) survived. This DC cell therapy could be readily translatable to humans, because we can generate large numbers of human EPS-DCs and use them as an "off the shelf" treatment for patients undergoing HSCT.
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Base de datos:
MEDLINE
Asunto principal:
Antígeno HLA-A2
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Enfermedad Injerto contra Huésped
Límite:
Animals
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Humans
Idioma:
En
Revista:
Transplant Cell Ther
Año:
2024
Tipo del documento:
Article