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

Ahmed A Shokeir; Amira Awadalla; Eman T Hamam; Abdelaziz M Hussein; Mohamed R Mahdi; Alyaa Naeem Abosteta; Mirna Shahin; Nashwa Barakat; Mohamed El-Adl; Mohamed El-Sherbiny; Mamdouh Eldesoqui; Moneer AlMadani; Sahar K Ali; El-Said El-Sherbini; Salma M Khirallah

doi:10.1016/j.abb.2024.109985

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

Arch Biochem Biophys. 2024 May:755:109985. doi: 10.1016/j.abb.2024.109985. Epub 2024 Apr 4.

Authors

Affiliations

¹ Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
² Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt; Nanomedicine Research Unit, Faculty of Medicine, Delta University for Science and Technology, Gamasa, Egypt.
³ Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
⁴ Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt; Department of Basic Medical Sciences, Faculty of Medicine, Galala University, Suez, Egypt.
⁵ Biochemistry Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
⁶ Mansoura Manchester Medical Program for Medical Education, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
⁷ Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
⁸ Departement of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
⁹ Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Diriyah, 13713, Riyadh, Saudi Arabia.
¹⁰ Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt; Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Diriyah, 13713, Riyadh, Saudi Arabia.
¹¹ Department of Clinical Medical Sciences, College of Medicine, AlMaarefa University, Diriyah, 13713, Riyadh, Saudi Arabia.
¹² Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt.
¹³ Chemistry Department (Biochemistry Division), Faculty of Science, Port Said University, Port Said, 42526, Egypt. Electronic address: s.mostafa@sci.psu.edu.eg.

PMID: 38579957
DOI: 10.1016/j.abb.2024.109985

Abstract

Objective: To determine whether WJ-MSCs pretreated with VPA would enhance their migration to improve functional recovery of renal IRI in rats.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: AKT; CXCR4; IRI; Valproic acid; WJ-MSCs.