Hepatoprotective Effects of Hyaluronic Acid-Preconditioned Bone Marrow Mesenchymal Stem Cells against Liver Toxicity via the Inhibition of Apoptosis and the Wnt/β-Catenin Signaling Pathway
Amira Awadalla,
Eman T. Hamam,
Sally Abdallah Mostafa,
Seham Ahmed Mahmoud,
Khalid Mohamed Elazab,
Ahmed Mohamed El Nakib,
Mamdouh Eldesoqui,
Mohamed El-Sherbiny,
Omar A. Ammar,
Rasha Hamed Al-Serwi,
Mohamed A. Saleh,
Amira Sarhan,
Mohamed Ali
Affiliations
Amira Awadalla
Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt
Eman T. Hamam
Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt
Sally Abdallah Mostafa
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
Seham Ahmed Mahmoud
Chemistry Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt
Khalid Mohamed Elazab
Department of Biology, Faculty of Science, Jazan University, Jazan 82511, Saudi Arabia
Ahmed Mohamed El Nakib
Department of Tropical Medicine, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
Mamdouh Eldesoqui
Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
Mohamed El-Sherbiny
Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia
Omar A. Ammar
Basic Science Department, Delta University for Science and Technology, Gamasa 35712, Egypt
Rasha Hamed Al-Serwi
Department of Basic Dental Sciences, College of Dentistry, Princess Nourahbint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
Mohamed A. Saleh
Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
Amira Sarhan
Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt
Background: Doxorubicin (DOX) is widely used to treat a variety of malignancies in both adults and children, including those of the bladder, breast, stomach, and ovaries. Despite this, it has been reported to cause hepatotoxicity. The recent discovery of bone marrow-derived mesenchymal stem cells’ (BMSCs) therapeutic effects in the context of liver diseases suggests that their administration plays a part in the mitigation and rehabilitation of drug-induced toxicities. Objectives: This study investigated whether bone BMSCs could reduce DOX-induced liver damage by blocking the Wnt/β-catenin pathway that causes fibrotic liver. Materials and methods: BMSCs were isolated and treated with hyaluronic acid (HA) for 14 days before injection. Thirty-five mature male SD rats were categorized into four groups; group one (control) rats were supplemented with saline 0.9% for 28 days, group two (DOX) rats were injected with DOX (20 mg/kg), group three (DOX + BMSCs) rats were injected with 2 × 106 BMSCs after 4 days of DOX injection, group four (DOX + BMSCs + HA) rats were injected with 0.1 mL BMSCs pretreated with HA after 4 days of DOX. After 28 days the rats were sacrificed, and blood and liver tissue samples were subjected to biochemical and molecular analysis. Morphological and immunohistochemical observations were also carried out. Results: In terms of liver function and antioxidant findings, cells treated with HA showed considerable improvement compared to the DOX group (p p < 0.05). Conclusion: Our findings proved that BMSCs treated with HA exert their paracrine therapeutic effects via their secretome, suggesting that cell-based regenerative therapies conditioned with HA may be a viable alternative to reduce hepatotoxicity.
