Therapeutic efficacy of extracellular vesicles to suppress allograft rejection in preclinical kidney transplantation models: A systematic review and meta-analysis.

ABSTRACT

BACKGROUND: Kidney transplantation is the optimal treatment of end-stage renal disease. Extracellular vesicles (EVs) have tremendous therapeutic potential, but their role in modulating immune responses in kidney transplantation remains unclear. METHODS: We performed a systematic review and meta-analysis to investigate the therapeutic efficacy of EVs in preclinical kidney transplant models. Outcomes for meta-analysis were graft survival and renal function. Subgroup analysis was conducted between immune cell derived EVs (immune cell-EVs) and mesenchymal stromal cell derived EVs (MSC-EVs). RESULTS: Seven studies published from 2013 to 2021 were included. The overall effects showed that EVs had a positive role in prolonging allograft survival (standardized mean difference (SMD) = 2.00; 95% confidence interval (CI), 0.79 to 3.21; P < 0.01; I2 = 94%), reducing serum creatinine (SCr) (SMD = -2.19; 95%CI, -3.35 to -1.04; P < 0.01; I2 = 93%) and blood urea nitrogen (BUN) concentrations (SMD = -1.69; 95%CI, -2.98 to -0.40; P = 0.01; I2 = 94%). Subgroup analyses indicated that only immune cell-EVs significantly prolonged graft survival and improve renal function but not MSC-EVs. CONCLUSIONS: EVs are promising candidates to suppress allograft rejection and improve kidney transplant outcome. Immune cell-EVs showed their superiority over MSC-EVs in prolonging graft survival and improving renal function. For interpretation of the outcomes, additional studies are needed to validate these findings.