Human leukocyte antigen selected allogeneic mesenchymal stromal cell therapy in renal transplantation: The Neptune study, a phase I single-center study.
Am J Transplant
; 20(10): 2905-2915, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32277568
ABSTRACT
Mesenchymal stromal cells (MSC) hold promise as a novel immune-modulatory therapy in organ transplantation. First clinical studies have used autologous MSCs; however, the use of allogeneic "off-the-shelf" MSCs is more sustainable for broad clinical implementation, although with the risk of causing sensitization. We investigated safety and feasibility of allogeneic MSCs in renal transplantation, using a matching strategy that prevented repeated mismatches. Ten patients received two doses of 1.5 × 106 /kg allogeneic MSCs 6 months after transplantation in a single-center nonrandomized phase Ib trial, followed by lowering of tacrolimus (trough level 3 ng/mL) in combination with everolimus and prednisone. Primary end point was safety, measured by biopsy proven acute rejection (BPAR) and graft loss 12 months after transplantation. Immune monitoring was performed before and after infusion. No BPAR or graft loss occurred and renal function remained stable. One patient retrospectively had DSAs against MSCs, formed before infusion. No major alterations in T and B cell populations or plasma cytokines were observed upon MSC infusion. Administration of HLA selected allogeneic MSCs combined with low-dose tacrolimus 6 months after transplantation is safe at least in the first year after renal transplantation. This sets the stage to further explore the efficacy of third-party MSCs in renal transplantation.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Transplante de Rim
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Transplante de Células-Tronco Hematopoéticas
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Transplante de Células-Tronco Mesenquimais
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Células-Tronco Mesenquimais
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Am J Transplant
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Holanda