Because of their capability to self-renew and differentiate into functional parenchyma, transplantation of stem/progenitor cells is considered a promising therapeutic strategy for AKI.

Accordingly, exploring a new and potent therapeutic strategy is imperative.Īn increasing number of investigations in the field of regenerative medicine have focused on the use of stem/progenitor cells in promoting the recovery of AKI. Despite significant advancements in technology associated with supportive renal replacement therapy, the prognosis and the mortality rate have not been improved. Due to a lack of efficient therapies, ischemia/reperfusion injury-induced AKI has a high mortality rate reaching 50% and significantly contributes to the burden of end-stage renal disease. The pathophysiology of renal ischemia/reperfusion injury consists of renal hemodynamic change, renal hypoxia, inflammatory response, and injuries of kidney endothelial and tubular cells. It inevitably occurs in clinical procedures, including allograft renal transplantation, partial nephrectomy, and clinical conditions including hypovolemic shock, hypotension, dehydration, and acute tubular necrosis. Renal ischemia/reperfusion injury is the major cause of intrinsic acute kidney injury (AKI). More preclinical studies and thoughtfully designed animal studies are needed in the future. However, the current systematic review and meta-analysis did not identify significant influential factors associated with treatment effects. These vesicles may help (i) reduce cell apoptosis and stimulate cell proliferation, (ii) ameliorate inflammatory injury and renal fibrosis, (iii) promote angiogenesis, and (iv) inhibit oxidative stress. Stem/progenitor cell-EVs are effective in improving renal function in rodent ischemia/reperfusion injury-induced AKI model.

Significant publication bias was observed (Egger’s test, P < 0.001). The pooled results showed that EV injection could lead to a remarkable sCr reduction compared with the control group (SMD, − 3.47 95%CI, − 4.15 to − 2.80 P 0.05). ResultsĪ total of 30 studies with 985 ischemia/reperfusion injury-induced AKI rodent models were included. A standardized mean difference (SMD) was used as the common effect size between stem/progenitor cell-EV-treated and control groups, with values of 0.2, 0.5, 0.8, and 1.0 defined as small, medium, large, and very large effect sizes, respectively. Sensitivity analysis, cumulative meta-analysis, and assessment of publication bias were also performed in our systematic review and meta-analysis. Meta-regression analysis was used to reveal the influential factors of EV therapy. The level of SCr, an indicator of renal function, was regarded as the primary outcome. MethodsĪ literature search was performed in PubMed, Embase, Scopus, and Web of Science to identify controlled studies about the therapeutic efficiency of stem/progenitor cell-EVs on ischemia/reperfusion injury-induced AKI rodent models. Here, we performed this systematic review and meta-analysis to assess the stem/progenitor cell-EV efficacy in treating ischemia/reperfusion injury-induced AKI in preclinical rodent models.

However, their regulatory effects remain poorly understood, and their therapeutic efficiency in clinical trials is controversial. Extracellular vesicles (EVs), especially for stem/progenitor cell-derived EVs (stem/progenitor cell-EVs), have emerged as a promising therapy for ischemia/reperfusion injury-induced AKI. Acute kidney injury (AKI) induced by ischemia/reperfusion injury significantly contribute to the burden of end-stage renal disease.

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