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Published on: February 2, 2021
Extracellular vesicles for acute kidney injury in preclinical rodent models: a meta-analysis
Chao Liu1, Jin Wang1, Jie Hu2,3
1Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, China.
Introduction:
Extracellular vesicles (EVs), especially stem cell-derived EVs, have emerged as a potential novel therapy for acute kidney injury (AKI). However, their effects remain incompletely understood. Therefore, we performed this meta-analysis to systematically review the efficacy of EVs on AKI in preclinical rodent models.
Methods:
We searched PubMed, EMBASE, and the Web of Science up to March 2019 to identify studies that reported the treatment effects of EVs in a rodent AKI model. The primary outcome was serum creatinine (Scr) levels. The secondary outcomes were the blood urea nitrogen (BUN) levels, renal injury score, percentage of apoptotic cells, and interleukin (IL)-10 and tumour necrosis factor (TNF)-α levels. Two authors independently screened articles based on the inclusion and exclusion criteria. The meta-analysis was conducted using RevMan 5.3 and R software.
Results:
Thirty-one studies (n = 552) satisfied the inclusion criteria. Pooled analyses demonstrated that the levels of Scr (SMD = - 3.71; 95% CI = - 4.32, - 3.10; P < 0.01), BUN (SMD = - 3.68; 95% CI = - 4.42, - 2.94; P < 0.01), and TNF-α (SMD = - 2.65; 95% CI = - 4.98, - 0.32; P < 0.01); the percentage of apoptotic cells (SMD = - 6.25; 95% CI = - 8.10, - 4.39; P < 0.01); and the injury score (SMD = - 3.90; 95% CI = - 5.26, - 2.53; P < 0.01) were significantly decreased in the EV group, and the level of IL-10 (SMD = 2.10; 95% CI = 1.18, 3.02; P < 0.01) was significantly increased. Meanwhile, no significant difference was found between stem cell-derived EVs and stem cells.
Conclusion:
The present meta-analysis confirmed that EV therapy could improve renal function and the inflammatory response status and reduce cell apoptosis in a preclinical rodent AKI model. This provides important clues for human clinical trials on EVs.
Insights
Extracellular vesicles (EVs) show promise in treating acute kidney injury (AKI) by improving kidney function and reducing inflammation in rodent models. This meta-analysis supports further investigation into EVs as a potential therapy for AKI.
Area of Science:
- Biomedical research
- Regenerative medicine
- Nephrology
Background:
- Acute kidney injury (AKI) poses a significant clinical challenge with limited therapeutic options.
- Extracellular vesicles (EVs), particularly those derived from stem cells, are emerging as a promising cell-free therapeutic strategy.
- The precise therapeutic effects of EVs in AKI models require systematic evaluation.
Purpose of the Study:
- To systematically review and meta-analyze the efficacy of extracellular vesicles (EVs) in preclinical rodent models of acute kidney injury (AKI).
- To assess the impact of EV therapy on key biomarkers of kidney function, renal injury, and inflammation.
Main Methods:
- A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science up to March 2019.
- Thirty-one studies involving rodent AKI models treated with EVs were included in the meta-analysis.
- Primary outcomes included serum creatinine (Scr) and blood urea nitrogen (BUN) levels; secondary outcomes comprised renal injury score, apoptosis, and cytokine levels (IL-10, TNF-α).
Main Results:
- Pooled analysis of 31 studies (n=552) demonstrated significant reductions in Scr, BUN, renal injury scores, and apoptotic cells following EV treatment.
- EV therapy led to a significant decrease in TNF-α and a significant increase in IL-10 levels, indicating modulation of the inflammatory response.
- No significant differences in efficacy were observed between stem cell-derived EVs and direct stem cell administration.
Conclusions:
- Extracellular vesicle therapy effectively improves renal function and ameliorates the inflammatory state in preclinical rodent models of AKI.
- EVs demonstrate a capacity to reduce cellular apoptosis, contributing to renoprotection.
- These findings provide crucial evidence supporting the potential of EV-based therapies for human clinical trials in AKI treatment.
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