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Abstract The present study was designed to investigate the regenerative efficacy of breast milk mesenchymal stem cells in rats with nephropathy and to address the potential molecular mechanisms involved in the reparative modalities of these cells in relation to cellular autophagy. The effect of Br-MSCs was represented in improving the level of urea nitrogen in the blood in addition to creatinine and uric acid. It also improved renal oxidative stress, which was evident in the decrease in MDA. It also led to an increase in antioxidant activity, represented by an increase in CAT, SOD, and Gpx. hBr-MSCs administration significantly upregulated the expression of the autophagic flux inducers LC3-II and beclin-1 and downregulated the autophagy inhibitor P62, mTOR, and mir-377. Also, Br-MSCs administration downregulation in the expression of the profibrotic markers TGF-β, NF-κβ, and Smad-3 and upregulation in the antifibrotic markers Smad-7 and microRNA let-7b than the AKI group. Beside, an improvement of renal histoarchitecture detected in significantly decrement of tubulointerstitial injury scores, down-regulated collagen synthesis and deposition, significantly up-regulated renal insulin growth factor 1, epidermal growth factor receptor 1, and autophagy-promoting factor beclin-1.Ultrastructurally, marked restoration of macroautophagy in the Podocytes and PST represented by the numerous initial autophagosome and degradative one.. Finally, it was concluded that hBr-MSCs have the ability to regenerate damaged kidney tissues through a paracrine effect, as many growth factors are secreted that enhance the kidney autophagy process. |