TY - JOUR
T1 - A systematic review and meta-analysis of cell-based interventions in experimental diabetic kidney disease
AU - Hickson, La Tonya J.
AU - Abedalqader, Tala
AU - Ben-Bernard, Gift
AU - Mondy, Jayla M.
AU - Bian, Xiaohui
AU - Conley, Sabena M.
AU - Zhu, Xiangyang
AU - Herrmann, Sandra M.
AU - Kukla, Aleksandra
AU - Lorenz, Elizabeth C.
AU - Kim, Seo Rin
AU - Thorsteinsdottir, Bjorg
AU - Lerman, Lilach O.
AU - Murad, M. Hassan
N1 - Funding Information:
The authors thank Patricia J. Erwin, MLS (multi‐database literature search); Shane A. Bobart, MD (literature search), Donna K. Lawson, CCRP, LPN (database maintenance), Cody C. Gowan (cell processing reviews), and Shannon Meier (secretarial support). L.J.H. takes full responsibility for the work. This project was supported by funding from Regenerative Medicine Minnesota RMM 091718CT (L.J.H.), Mayo Clinic Florida Center for Regenerative Medicine (L.J.H.), National Institute of Health (NIH) grants DK109134 and DK123492 (L.J.H.), NIDDK Diabetes Complications Consortium (RRID:SCR‐001415; DK076169, DK115255); UL1 TR002377 (L.J.H.; Mayo Clinic CCaTS UL1TR002377; REDCap), and the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (L.J.H.). Additional support was provided by NIH grants DK102325 (LOL), DK07013 (SMC), Burroughs Wellcome Fund (SMC); DK118120 (SMH); DK101405 (nuSURF: Mayo; J.M.M.; G.B.B.). Summer Program for International Research Internship Training (SPIRIT) Alfaisal University, Riyadh, Saudi Arabia (AT). Publication content is solely the responsibility of the authors and does not necessarily represent the official views of Satellite Healthcare, Regenerative Medicine Minnesota, or the NIH.
Funding Information:
The authors thank Patricia J. Erwin, MLS (multi-database literature search); Shane A. Bobart, MD (literature search), Donna K. Lawson, CCRP, LPN (database maintenance), Cody C. Gowan (cell processing reviews), and Shannon Meier (secretarial support). L.J.H. takes full responsibility for the work. This project was supported by funding from Regenerative Medicine Minnesota RMM 091718CT (L.J.H.), Mayo Clinic Florida Center for Regenerative Medicine (L.J.H.), National Institutes of Health (NIH) grants DK109134 and DK123492 (L.J.H.), NIDDK Diabetes Complications Consortium (RRID:SCR-001415; DK076169, DK115255); UL1 TR002377 (L.J.H.; Mayo Clinic CCaTS UL1TR002377; REDCap), and the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (L.J.H.). Additional support was provided by NIH grants DK102325 (LOL), DK07013 (SMC), Burroughs Wellcome Fund (SMC); DK118120 (SMH); DK101405 (nuSURF: Mayo; J.M.M.; G.B.B.). Summer Program for International Research Internship Training (SPIRIT) Alfaisal University, Riyadh, Saudi Arabia (AT). Publication content is solely the responsibility of the authors and does not necessarily represent the official views of Satellite Healthcare, Regenerative Medicine Minnesota, or the NIH.
Funding Information:
L.O.L. received grant funding from Novo Nordisk and is an advisor to Weijian Technologies and AstraZeneca. All other authors declared no financial conflicts of interest.
Publisher Copyright:
© 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - apoptosis
KW - chronic kidney disease
KW - diabetes
KW - diabetic nephropathy
KW - extracellular vesicles
KW - inflammation
KW - mesenchymal stem cells
KW - stem cells
KW - umbilical cord blood
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U2 - 10.1002/sctm.19-0419
DO - 10.1002/sctm.19-0419
M3 - Review article
C2 - 34106528
AN - SCOPUS:85107798412
SN - 2157-6564
VL - 10
SP - 1304
EP - 1319
JO - Stem cells translational medicine
JF - Stem cells translational medicine
IS - 9
ER -