Abstract
Cardio-renal syndrome (CRS) denotes the convergence of heart-kidney interactions across several mechanisms. The current study is conducted to evaluate the anti-inflammatory role of adipose tissue-derived stem cells (ASCs) versus adipose stem cell-derived extracellular vesicles (ADSCs-EVs) in experimental model of cardiorenal syndrome type III. The study was conducted on 50 male rats that were equally divided to: group I (control group); Group II (experimental cardiorenal syndrome group) which induced by right renal artery ligation (ICRSIII); Group III (Sham-operated control group) which underwent surgical incision without renal artery ligation; Group IV (ICRSIII which received ADSCs-extracellular vesicles (ADSCs-EVs); Group V (ICRSIII which received adipose tissue stem cells (ASCs). Assessment of pro-inflammatory cytokines; IL-10, IL-1α, IL-6, IL-1 β, IFN-γ, NF-α and their mRNA gene expression quantitation, (NGAL), and brain natriuretic peptide (BNP) as markers of cardiac dysfunction, as well as histopathological examination of renal tissue was examined by H& E, Masson trichrome and periodic acid-Schiff stains (PAS). The ICRS group exhibited significant acute tubular injury with tubular dilation, loss of brush borders, epithelial flattening, and occasional sloughed cells in lumen. Use of either ADSCs-EVs or ASCs significantly ameliorated the histological findings of tubular injury. Proinflammatory cytokines, BNP and NGAL were significantly elevated in ICRSIII group as compared to all other studied groups. Administration of ADSCs-EVs or ASCs led to significant decrease in all proinflammatory cytokines as well as BNP and NGAL levels with no significant difference between them. In conclusion, ADSCs-EXs and ASCs exhibited significant repairing effects in experimental-induced cardiorenal syndrome type III as evidenced by amelioration of histological findings of tubular injury, anti-inflammatory effects, and the significant decrease in markers of cardiac dysfunction. ADSC-EVs reprogramed injured cardiac cells by activating regenerative processes.
•Cardiorenal syndrome type III is a category of CRS in which acute kidney injury (AKI) could lead to the development of acute dysfunction in the heart.•Cardio-renal syndrome describes a range of disorders affecting both the heart and kidneys in which an dysfunction in one organ may lead to an acute or chronic dysfunction in the other organ.•Adipose stem cells produce improvement in kidney function in rats with cardio-renal syndrome type III • Injected cells engraftment decreased tubular cells apoptosis and mitigate pro-inflammatory milieu.•ADSCs-EXs and ASCs exhibited repairing effects in cardiorenal syndrome type III by amelioration of histological findings of tubular injury, anti-inflammatory effects, and the significant decrease in markers of cardiac dysfunction.•Reduction of NGAL-MMP9 complexes prevented further negative heart remodeling.