Administration of Mesenchymal Stem Cells in Diabetic Kidney Disease: a Systematic Review and Meta-analysis

Overview

Journal Stem Cell Res Ther

Publisher Biomed Central

Date 2021 Jan 8

PMID 33413678

Citations 14

Authors

Wenshan Lin

Hong-Yan Li

Qian Yang

Guangyong Chen

Shujun Lin

Chunling Liao

Tianbiao Zhou

Affiliations

Soon will be listed here.

Abstract

Background: Mesenchymal stem cell (MSC) therapy shows great promise for diabetic kidney disease (DKD) patients. Research has been carried out on this topic in recent years. The main goals of this paper are to evaluate the therapeutic effects of MSCs on DKD through a meta-analysis and address the mechanism through a systematic review of the literature.

Method: An electronic search of the Embase, Cochrane Library, ISI Web of Science, PubMed, and US National Library of Medicine (NLM) databases was performed for all articles about MSC therapy for DKD, without species limitations, up to January 2020. Data were pooled for analysis with Stata SE 12.

Result: The MSC-treated group showed a large and statistically significant hypoglycemic effect at 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, and 6 months. Total hypoglycemic effect was observed (SMD = - 1.954, 95%CI - 2.389 to - 1.519, p < 0.001; I = 85.1%). The overall effects on serum creatinine (SCr) and blood urea nitrogen (BUN) were analyzed, suggesting that MSC decreased SCr and BUN and mitigated the impairment of renal function (SCr: SMD = - 4.838, 95%CI - 6.789 to - 2.887, p < 0.001; I = 90.8%; BUN: SMD = - 4.912, 95%CI - 6.402 to - 3.422, p < 0.001; I = 89.3%). Furthermore, MSC therapy decreased the excretion of urinary albumin. Fibrosis indicators were assessed, and the results showed that transforming growth factor-β, collagen I, fibronectin, and α-smooth muscle actin were significantly decreased in the MSC-treated group compared to the control group.

Conclusion: MSCs might improve glycemic control and reduce SCr, BUN, and urinary protein. MSCs can also alleviate renal fibrosis. MSC therapy might be a potential treatment for DKD.

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References

Panes J, Garcia-Olmo D, Van Assche G, Colombel J, Reinisch W, Baumgart D . Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology. 2017; 154(5):1334-1342.e4. DOI: 10.1053/j.gastro.2017.12.020. View

Barbado J, Tabera S, Sanchez A, Garcia-Sancho J . Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for lupus nephritis. Lupus. 2018; 27(13):2161-2165. DOI: 10.1177/0961203318804922. View

Ezquer F, Ezquer M, Simon V, Pardo F, Yanez A, Carpio D . Endovenous administration of bone-marrow-derived multipotent mesenchymal stromal cells prevents renal failure in diabetic mice. Biol Blood Marrow Transplant. 2009; 15(11):1354-65. DOI: 10.1016/j.bbmt.2009.07.022. View

Wang S, Li Y, Zhao J, Zhang J, Huang Y . Mesenchymal stem cells ameliorate podocyte injury and proteinuria in a type 1 diabetic nephropathy rat model. Biol Blood Marrow Transplant. 2013; 19(4):538-46. DOI: 10.1016/j.bbmt.2013.01.001. View

Rashed L, Elattar S, Eltablawy N, Ashour H, Mahmoud L, El-Esawy Y . Mesenchymal stem cells pretreated with melatonin ameliorate kidney functions in a rat model of diabetic nephropathy. Biochem Cell Biol. 2018; 96(5):564-571. DOI: 10.1139/bcb-2017-0230. View

Yu S, Cheng Y, Zhang L, Yin Y, Xue J, Li B . Treatment with adipose tissue-derived mesenchymal stem cells exerts anti-diabetic effects, improves long-term complications, and attenuates inflammation in type 2 diabetic rats. Stem Cell Res Ther. 2019; 10(1):333. PMC: 6868748. DOI: 10.1186/s13287-019-1474-8. View

Chen S, Du K, Zou C . Current progress in stem cell therapy for type 1 diabetes mellitus. Stem Cell Res Ther. 2020; 11(1):275. PMC: 7346484. DOI: 10.1186/s13287-020-01793-6. View

Song I, Jung K, Lee T, Kim J, Sung E, Bae Y . Mesenchymal stem cells attenuate adriamycin-induced nephropathy by diminishing oxidative stress and inflammation via downregulation of the NF-kB. Nephrology (Carlton). 2017; 23(5):483-492. DOI: 10.1111/nep.13047. View

Papazova D, Oosterhuis N, Gremmels H, van Koppen A, Joles J, Verhaar M . Cell-based therapies for experimental chronic kidney disease: a systematic review and meta-analysis. Dis Model Mech. 2015; 8(3):281-93. PMC: 4348565. DOI: 10.1242/dmm.017699. View

10.

Rosselli D, Mumaw J, Dickerson V, Brown C, Brown S, Schmiedt C . Efficacy of allogeneic mesenchymal stem cell administration in a model of acute ischemic kidney injury in cats. Res Vet Sci. 2016; 108:18-24. DOI: 10.1016/j.rvsc.2016.07.003. View

11.

Xian Y, Lin Y, Cao C, Li L, Wang J, Niu J . Protective effect of umbilical cord mesenchymal stem cells combined with resveratrol against renal podocyte damage in NOD mice. Diabetes Res Clin Pract. 2019; 156:107755. DOI: 10.1016/j.diabres.2019.05.034. View

12.

Ezquer F, Ezquer M, Parrau D, Carpio D, Yanez A, Conget P . Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type 1 diabetic mice. Biol Blood Marrow Transplant. 2008; 14(6):631-40. DOI: 10.1016/j.bbmt.2008.01.006. View

13.

Xuan K, Li B, Guo H, Sun W, Kou X, He X . Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Sci Transl Med. 2018; 10(455). DOI: 10.1126/scitranslmed.aaf3227. View

14.

Togel F, Zhang P, Hu Z, Westenfelder C . VEGF is a mediator of the renoprotective effects of multipotent marrow stromal cells in acute kidney injury. J Cell Mol Med. 2009; 13(8B):2109-2114. PMC: 4940776. DOI: 10.1111/j.1582-4934.2008.00641.x. View

15.

Nagaishi K, Mizue Y, Chikenji T, Otani M, Nakano M, Konari N . Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes. Sci Rep. 2016; 6:34842. PMC: 5056395. DOI: 10.1038/srep34842. View

16.

Abdel Aziz M, Wassef M, Hosni Ahmed H, Rashed L, Mahfouz S, Aly M . The role of bone marrow derived-mesenchymal stem cells in attenuation of kidney function in rats with diabetic nephropathy. Diabetol Metab Syndr. 2014; 6(1):34. PMC: 4007638. DOI: 10.1186/1758-5996-6-34. View

17.

Yu M, Liu W, Li J, Lu J, Lu H, Jia W . Exosomes derived from atorvastatin-pretreated MSC accelerate diabetic wound repair by enhancing angiogenesis via AKT/eNOS pathway. Stem Cell Res Ther. 2020; 11(1):350. PMC: 7425015. DOI: 10.1186/s13287-020-01824-2. View

18.

Fang Y, Tian X, Bai S, Fan J, Hou W, Tong H . Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38 MAPK signaling pathway. Int J Mol Med. 2012; 30(1):85-92. DOI: 10.3892/ijmm.2012.977. View

19.

Lee S, Jang J, Kim H, Jung M, Ko M, Kim M . Mesenchymal stem cells prevent the progression of diabetic nephropathy by improving mitochondrial function in tubular epithelial cells. Exp Mol Med. 2019; 51(7):1-14. PMC: 6802630. DOI: 10.1038/s12276-019-0268-5. View

20.

Jurado M, De La Mata C, Ruiz-Garcia A, Lopez-Fernandez E, Espinosa O, Remigia M . Adipose tissue-derived mesenchymal stromal cells as part of therapy for chronic graft-versus-host disease: A phase I/II study. Cytotherapy. 2017; 19(8):927-936. DOI: 10.1016/j.jcyt.2017.05.002. View