Allogeneic mesenchymal stem cell as induction therapy to prevent both delayed graft function and acute rejection in
Qipeng Sun1, Liangqing Hong1, Zhengyu Huang1
1Department 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.
Background:
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 × 106 per kilogram human umbilical-cord-derived MSCs (UC-MSCs) via peripheral vein injection preoperatively, and a dose of 5 × 106 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.
Discussion:
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.
Trial Registration:
ClinicalTrials.gov, NCT02490020 . Registered on 29 June 2015.
Insights
This study investigates using umbilical cord-derived mesenchymal stem cells (UC-MSCs) as induction therapy to prevent delayed graft function and acute rejection in deceased-donor kidney transplants. Findings will determine if UC-MSCs are a safe and effective treatment option.
Area of Science:
- Transplantation immunology
- Regenerative medicine
- Nephrology
Background:
- Deceased-donor kidney transplantation is crucial but faces challenges with delayed graft function (DGF) and acute rejection.
- Ischemia-reperfusion injury and immune responses are primary causes of DGF and rejection.
- Mesenchymal stem cells (MSCs) show potential for anti-inflammatory and regenerative effects in transplantation.
Purpose of the Study:
- To assess the clinical efficacy of allogeneic UC-MSCs as induction therapy in deceased-donor renal transplantation.
- To evaluate the simultaneous prevention of DGF and acute rejection using UC-MSCs.
- To determine the safety and feasibility of UC-MSCs in this context.
Main Methods:
- A prospective, multicenter controlled study involving 100 renal allograft recipients.
- The trial group (50 patients) received UC-MSCs preoperatively and during surgery.
- Outcomes measured include DGF, biopsy-proved acute rejection (BPAR), graft/recipient survival, and postoperative complications.
Main Results:
- Data collection and analysis are ongoing for DGF and BPAR incidence.
- Assessment of graft and recipient survival rates.
- Monitoring of severe postoperative complications such as infections and bleeding.
Conclusions:
- This study aims to clarify the clinical value of UC-MSCs in preventing DGF and acute rejection.
- It will provide evidence regarding the safety and feasibility of allogeneic MSCs as induction therapy in renal transplantation.
- Results will inform future clinical practice for deceased-donor kidney transplants.
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