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.

Details

Title
A systematic review and meta‐analysis of cell‐based interventions in experimental diabetic kidney disease
Author
Hickson, LaTonya J 1   VIAFID ORCID Logo  ; Tala Abedalqader 2 ; Gift Ben‐Bernard 2 ; Mondy, Jayla M 2 ; Bian, Xiaohui 3 ; Conley, Sabena M 3 ; Zhu, Xiangyang 2 ; Herrmann, Sandra M 2 ; Kukla, Aleksandra 2 ; Lorenz, Elizabeth C 4 ; Seo Rin Kim 2 ; Thorsteinsdottir, Bjorg 5 ; Lerman, Lilach O 2   VIAFID ORCID Logo  ; M. Hassan Murad 5 

1  Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida, USA; Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA; Kern Center Affiliate, Mayo Clinic, Rochester, Minnesota, USA 
2  Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA 
3  Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida, USA 
4  Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA; Kern Center Affiliate, Mayo Clinic, Rochester, Minnesota, USA 
5  Kern Center Affiliate, Mayo Clinic, Rochester, Minnesota, USA; Division of Preventative Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA 
Pages
1304-1319
Section
CONCISE REVIEW
Publication year
2021
Publication date
Sep 2021
Publisher
Oxford University Press
ISSN
21576564
e-ISSN
21576580
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1002/sctm.19-0419
ProQuest document ID
2563302072
Copyright
© 2021. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.