Working Paper Article Version 1 This version is not peer-reviewed

Pretreatment with Retinoic Acid Potentiates the Renoprotective Effect of Adipose Derived Mesenchymal Stem Cells against Cisplatin Induced Nephrotoxicity

Version 1 : Received: 10 July 2020 / Approved: 12 July 2020 / Online: 12 July 2020 (12:19:00 CEST)

How to cite: Ibrahim, F.Z.M.; Barakat, N.M.; El-Deen, I.M.; khedr, M.M.M. Pretreatment with Retinoic Acid Potentiates the Renoprotective Effect of Adipose Derived Mesenchymal Stem Cells against Cisplatin Induced Nephrotoxicity. Preprints 2020, 2020070254 Ibrahim, F.Z.M.; Barakat, N.M.; El-Deen, I.M.; khedr, M.M.M. Pretreatment with Retinoic Acid Potentiates the Renoprotective Effect of Adipose Derived Mesenchymal Stem Cells against Cisplatin Induced Nephrotoxicity. Preprints 2020, 2020070254

Abstract

Background and Objectives: Therapeutic applications of stem cells are considered as an appropriate alternative in the treatment of many diseases, but the reduction in their survival after transplantation limit their clinical application that can be enhanced by chemical preconditioning. The present study investigated the effect of all-trans retinoic acid on survival, migration and angiogenesis of adipose derived stem cells in amelioration of cisplatin-induced acute kidney injury (AKI). Methods: Sprague-Dawley rats (180–220 g) (n=150) were divided into 5 major groups, 30 rats each. Group I: (negative control group). Group II: (Cisplatin ‘CIS’-treated group). Group III: (cisplatin and all-trans retinoic acid group). Group IV: (cisplatin and MSCs group). Group V: (cisplatin, ATRA and MSCs group). Ten rats were sacrificed at different time intervals in all groups at days 3, 7 and 11. Kidney tissue and blood samples were obtained. Renal function tests and oxidative stress parameters were studied; Molecular studies in addition to histopathological scoring systems for renal injury were analyzed. Results: ADMSCs isolation and characterization was done. ADMSCs preconditioning with ATRA enhanced the kidney function after cisplatin through decreasing serum creatinine and microalbuminuria, increasing creatinine clearance and return the antioxidant balance by decreasing NO and increasing SOD. ATRA also could reduce the inflammation, apoptosis and stimulate the angiogenesis by decreasing TGFB1, caspase-3 and increasing HIF1. The use of ADMSCs pretreated with ATRA was associated with significantly regenerative changes in kidney. Conclusion: ATRA increased ADMSCs viability and efficacy that leaded to amelioration of kidney functions through the reduction of oxidative stress, increase of antioxidant enzyme activity and reduction of apoptosis.

Subject Areas

Cisplatin; ADMSCs; ATRA; AKI; angiogenesis

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