Human Wharton's jelly-derived mesenchymal stromal stem cells preconditioned with valproic acid promote cell migration and reduce renal inflammation in ischemia/reperfusion injury by activating the AKT/P13K and SDF1/CXCR4 pathways

To determine whether WJ-MSCs pretreated with VPA would enhance their migration to improve functional recovery of renal IRI in rats. 150 Sprague-Dawley rats were distributed into 5 groups; Sham, IRI, WJ-MSC, VPA, and WJ-MSCs + VPA. 10 rats were sacrificed after 3, 5, and 7 days. Role of WJ-MSCs pretreated with VPA was evaluated by assessment of renal function, antioxidant enzymes together with renal histopathological and immunohistopathological analyses and finally by molecular studies. WJ-MSCs and VPA significantly improved renal function and increased antioxidants compared to IRI group. Regarding gene expression, WJ-MSCs and VPA decreased BAX and TGF-β1, up-regulated Akt, PI3K, BCL2, SDF1α, and CXCR4 related to IRI. Additionally, WJ-MSCs pretreated with VPA improved the measured parameters more than either treatment alone. WJ-MSCs isolated from the umbilical cord and pretreated with VPA defended the kidney against IRI by more easily homing to the site of injury. [Display omitted] •Valproic acid enhanced WJ-MSCs migration and improved functional recovery of renal IRI.•WJ-MSCs pretreated with VPA showed stimulation of the anti-inflammatory signaling pathway by PI3K/AKT activation.•WJ-MSCs pretreated with VPA increased BCL2 and inhibited BAX expression.•WJ-MSCs pretreated with VPA displayed a significant anti-fibrotic effect through the inhibition of TGFβ1.•WJ-MSCs pretreated with VPA revealed a chemotactic effect via an increase of SDF-1 and CXCR4 expression.•WJ-MSCs pretreated with VPA are a promising candidate for kidney protection against IRI.