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Updated: Nov 2, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
A systematic review and meta-analysis of cell-based interventions in experimental diabetic kidney disease
LaTonya J Hickson1,2,3, Tala Abedalqader2, Gift Ben-Bernard2
1Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida, USA.
Abstract:
Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this systematic review and meta-analysis summarized the effect of cell-based interventions in DKD animal models and treatment-related factors modifying outcomes. Electronic databases were searched for original investigations applying cell-based therapy in diabetic animals with kidney endpoints (January 1998-May 2019). Weighted or standardized mean differences were estimated for kidney outcomes and pooled using random-effects models. Subgroup analyses tested treatment-related factor effects for outcomes (creatinine, urea, urine protein, fibrosis, and inflammation). In 40 studies (992 diabetic rodents), therapy included mesenchymal stem/stromal cells (MSC; 61%), umbilical cord/amniotic fluid cells (UC/AF; 15%), non-MSC (15%), and cell-derived products (13%). Tissue sources included bone marrow (BM; 65%), UC/AF (15%), adipose (9%), and others (11%). Cell-based therapy significantly improved kidney function while reducing injury markers (proteinuria, histology, fibrosis, inflammation, apoptosis, epithelial-mesenchymal-transition, oxidative stress). Preconditioning, xenotransplantation, and disease-source approaches were effective. MSC and UC/AF cells had greater effect on kidney function while cell products improved fibrosis. BM and UC/AF tissue sources more effectively improved kidney function and proteinuria vs adipose or other tissues. Cell dose, frequency, and administration route also imparted different benefits. In conclusion, cell-based interventions in diabetic animals improved kidney function and reduced injury with treatment-related factors modifying these effects. These findings may aid in development of optimal repair strategies through selective use of cells/products, tissue sources, and dose administrations to allow for successful adaptation of this novel therapeutic in human DKD.
Insights
Cell-based therapies show promise for diabetic kidney disease (DKD) by improving kidney function and reducing injury in animal models. Treatment factors like cell type and source significantly influence outcomes, guiding future human therapy development.
Area of Science:
- Regenerative Medicine
- Nephrology
- Translational Research
Background:
- Diabetic kidney disease (DKD) is a progressive condition lacking curative treatments.
- Cell-based therapies offer a potential regenerative approach for DKD.
- Systematic review and meta-analysis are needed to consolidate evidence for clinical translation.
Purpose of the Study:
- To systematically review and meta-analyze the efficacy of cell-based interventions in DKD animal models.
- To identify treatment-related factors that modify outcomes in cell therapy for DKD.
- To inform the development of optimal cell-based repair strategies for human DKD.
Main Methods:
- Systematic search of electronic databases for studies on cell therapy in diabetic animals with kidney endpoints (1998-2019).
- Meta-analysis of kidney outcomes (creatinine, urea, proteinuria, fibrosis, inflammation) using random-effects models.
- Subgroup analyses to assess the impact of treatment-related factors on outcomes.
Main Results:
- Forty studies involving 992 diabetic rodents were analyzed.
- Cell-based therapies, including mesenchymal stem/stromal cells (MSC) and umbilical cord/amniotic fluid cells (UC/AF), significantly improved kidney function and reduced injury markers.
- Specific cell types (MSC, UC/AF) and tissue sources (bone marrow, UC/AF) demonstrated greater efficacy; cell products were effective for fibrosis.
- Treatment factors such as preconditioning, xenotransplantation, cell dose, frequency, and administration route influenced outcomes.
Conclusions:
- Cell-based interventions effectively improve kidney function and reduce injury in preclinical DKD models.
- Treatment-related factors significantly modulate the therapeutic effects of cell-based therapies.
- Findings provide a basis for optimizing cell therapy strategies for human DKD treatment.
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