Meta-analysis study of the therapeutic impact of Mesenchymal stem cells derived exosomes for chronic kidney diseases

Abstract

Mesenchymal stem cell-derived exosomes (EXOs) represent a promising avenue for treating chronic kidney diseases (CKD), though their precise impact remains somewhat elusive. To address this gap, we conducted a systematic analysis, scouring databases and clinical trial repositories for relevant studies from 2019 to 2023. Seventeen papers were meticulously selected for their focus on mesenchymal stem cell-derived exosomes (MSC-EXOs) and their potential in CKD treatment. Our comprehensive meta-analysis, incorporating 15 preclinical and 6 clinical studies, underscores the efficacy of MSC-EXOs in improving renal function while attenuating tubular injury, inflammation, apoptosis, collagen deposition, and renal fibrosis. Notably, post-treatment with MSC-EXOs exhibited significant associations with various CKD markers, with pooled proportions indicating a considerable impact on blood urea nitrogen (BUN) and serum creatinine (SCR) levels. Subgroup analyses based on animal models further elucidated heterogeneity within the studies. In conclusion, MSC-EXOs demonstrate promise in enhancing renal function and reducing CKD risk, as evidenced by both preclinical and clinical data. Their efficacy in lowering SCR and BUN levels while enhancing filtration rate suggests MSC-EXOs as a viable and secure alternative to cell-based therapies, thereby providing valuable insights for personalized CKD treatments despite inherent limitations.

Keywords: Chronic kidney diseases; Exosome; Mesenchymal stem cells; Meta-analysis; Renal fibrosis.

Graphical abstract

Fig. 1

Study selection process according to PRISMA.

Fig. 2

Risk of bias.

Fig. 3

Forest plots of standardized mean differences (SMDs) with 95 % confidence intervals (CIs) for (A) BUN and (B) SCR levels following MSC-derived exosome treatment in CKD models. Statistical analysis was performed using a random-effects model, between-study heterogeneity was quantified using I², τ², and Cochran's Q test p-values. Effect sizes are shown for individual studies and pooled estimates. Negative SMD values indicate a reduction in renal biomarkers.

Fig. 4

Subgroup analysis based on animal model with their 95 % confidence intervals (A) efficacy in BUN reduction of MSC derived EXOs (B) efficacy in SCR reduction of MSC derived EXOs. Study heterogeneity was assessed using I², τ², and Cochran's Q test. Test for subgroup differences (χ² and p-values) are reported. Negative SMD values indicate a reduction in renal biomarkers, suggesting therapeutic benefit.

Fig. 5

Subgroup analysis based on source of exosome model with their 95 % confidence intervals (A) efficacy in BUN reduction of MSC derived EXOs (B) efficacy in SCR reduction of MSC derived EXOs. Study heterogeneity within subgroups was quantified using I², τ², and Q statistics. A test for subgroup differences (χ² and p-values) was performed to evaluate whether treatment efficacy varied significantly by exosome origin. Negative SMD values indicate therapeutic benefit through reduction in renal injury markers.