Department of Renal Transplantation, Lingnan Hospital, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China.
Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Tianhe Road 600, Guangzhou, 510630, People's Republic of China.
Trials. 2017 Nov 16;18(1):545. doi: 10.1186/s13063-017-2291-y.
Using kidneys from deceased donors is an available strategy to meet the growing need of grafts. However, higher incidences of delayed graft function (DGF) and acute rejection exert adverse effects on graft outcomes. Since ischemia-reperfusion injury (IRI) and ongoing process of immune response to grafts are the major causes of DGF and acute rejection, the optimal induction intervention should possess capacities of both repairing renal structure injury and suppressing immune response simultaneously. Mesenchymal stem cells (MSCs) with potent anti-inflammatory, regenerative and immune-modulatory properties are considered as a candidate to prevent both DGF and acute rejection in renal transplantation. Previous studies just focused on the safety of autologous MSCs on living-related donor renal transplants, and lack of concomitant controls and the sufficient sample size and source of MSCs. Here, we propose a prospective multicenter controlled study to assess the clinical value of allogeneic MSCs in preventing both DGF and acute rejection simultaneously as induction therapy in deceased-donor renal transplantation.
METHODS/DESIGN: Renal allograft recipients (n = 100) will be recruited and divided into trial and control groups, and 50 patients in the trial group will be administered with a dose of 2 × 10 per kilogram human umbilical-cord-derived MSCs (UC-MSCs) via peripheral vein injection preoperatively, and a dose of 5 × 10 cells via renal arterial injection during surgery, with standard induction therapy. Incidences of postoperative DGF and biopsy-proved acute rejection (BPAR) will be recorded and analyzed. Additionally, other clinical parameters such as baseline demographics, graft and recipient survival and other severe postoperative complications, including complicated urinary tract infection, severe pneumonia, and severe bleeding, will be also assessed.
This study will clarify the clinical value of UC-MSCs in preventing DGF and acute rejection simultaneously in deceased-donor renal transplantation, and provide evidence as to whether allogeneic MSCs can be used as clinically feasible and safe induction therapy.
ClinicalTrials.gov, NCT02490020 . Registered on 29 June 2015.
使用已故供者的肾脏是满足日益增长的移植物需求的一种可行策略。然而，延迟移植物功能（DGF）和急性排斥反应的发生率较高会对移植物的结果产生不利影响。由于缺血再灌注损伤（IRI）和对移植物持续的免疫反应是 DGF 和急性排斥反应的主要原因，最佳诱导干预措施应该同时具有修复肾结构损伤和抑制免疫反应的能力。间充质干细胞（MSCs）具有强大的抗炎、再生和免疫调节特性，被认为是预防肾移植中 DGF 和急性排斥反应的候选药物。以前的研究仅关注自体 MSCs 在活体相关供者肾移植中的安全性，缺乏伴随对照和足够的 MSC 样本量和来源。在这里，我们提出了一项前瞻性多中心对照研究，以评估同种异体 MSC 作为诱导治疗在已故供者肾移植中同时预防 DGF 和急性排斥反应的临床价值。
方法/设计：将招募 100 例肾移植受者，并将其分为试验组和对照组，试验组 50 例患者术前通过外周静脉注射 2×10 个/kg 人脐带源 MSC（UC-MSCs），术中通过肾动脉注射 5×10 个细胞，同时进行标准诱导治疗。记录和分析术后 DGF 和活检证实的急性排斥反应（BPAR）的发生率。此外，还将评估其他临床参数，如基线人口统计学、移植物和受者存活率以及其他严重术后并发症，包括复杂尿路感染、严重肺炎和严重出血。
本研究将阐明 UC-MSCs 在预防已故供者肾移植中 DGF 和急性排斥反应的同时的临床价值，并为同种异体 MSC 是否可作为临床可行和安全的诱导治疗提供证据。
ClinicalTrials.gov，NCT02490020。注册于 2015 年 6 月 29 日。
