干细胞治疗诱导肾移植 6 年的耐受经验。

Six years' experience of tolerance induction in renal transplantation using stem cell therapy.

机构信息

Department of Pathology, Lab Medicine, Transfusion Services & Immunohematology, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H.L. Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Civil Hospital Campus, Asarwa, Ahmedabad 380016, India; Department of Regenerative Medicine and Cell Therapy, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H.L. Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Civil Hospital Campus, Asarwa, Ahmedabad 380016, India.

Department of Regenerative Medicine and Cell Therapy, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H.L. Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Civil Hospital Campus, Asarwa, Ahmedabad 380016, India; Department of Nephrology and Transplantation Medicine, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H.L. Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Civil Hospital Campus, Asarwa, Ahmedabad 380016, India.

出版信息

Clin Immunol. 2018 Feb;187:10-14. doi: 10.1016/j.clim.2017.07.024. Epub 2017 Jul 27.

DOI:10.1016/j.clim.2017.07.024

PMID:28757451

Abstract

Tolerance induction (TI) has been attempted with chimerism/clonal deletion. We report results of TI protocol (TIP) using stem cell therapy (SCT) included adipose derived mesenchymal stem cells (AD-MSC) and hematopoietic stem cells (HSC) in 10 living-donor related renal transplantation (LDRT) patients under non-myeloablative conditioning with Bortezomib, Methylprednisone, rabbit-anti-thymoglobulin and Rituximab, without using conventional immunosuppression. Transplantation was performed following acceptable lymphocyte cross-match, flow cross-match, single antigen assay and negative mixed lymphocyte reaction (MLR). Monitoring included serum creatinine (SCr), donor specific antibodies (DSA) and MLR. Protocol biopsies were planned after 100days and yearly in willing patients. Rescue immunosuppression was planned for rejection/DSA/positive MLR. Over mean 6±0.37year follow-up patient survival was 80% and death-censored graft survival was 90%. Mean SCr was 1.44±0.41mg/dL. This is the first clinical report of sustained TI in LDRT for 6years using SCT.

摘要

耐受诱导（TI）已尝试通过嵌合/克隆删除。我们报告了使用干细胞治疗（SCT）的 TI 方案（TIP）的结果，该方案包括脂肪来源的间充质干细胞（AD-MSC）和造血干细胞（HSC），在非清髓性条件下使用硼替佐米、甲基强的松龙、兔抗胸腺球蛋白和利妥昔单抗，不使用常规免疫抑制。移植是在可接受的淋巴细胞交叉匹配、流式细胞交叉匹配、单抗原检测和阴性混合淋巴细胞反应（MLR）后进行的。监测包括血清肌酐（SCr）、供体特异性抗体（DSA）和 MLR。愿意的患者计划在 100 天后和每年进行方案活检。排斥反应/DSA/阳性 MLR 计划进行挽救性免疫抑制。在平均 6±0.37 年的随访中，患者存活率为 80%，死亡时移植物存活率为 90%。平均 SCr 为 1.44±0.41mg/dL。这是首例使用 SCT 在 LDRT 中进行持续 6 年的 TI 的临床报告。