Mesenchymal stem-cells' exosomes are renoprotective in postmenopausal chronic kidney injury via reducing inflammation and degeneration.

Autor: Alasmari WA; Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, Makkah, 24230, Saudi Arabia., El-Shetry ES; Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, Egypt., Ibrahim D; Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Zagazig University, 44511, Zagazig, Egypt., ElSawy NA; Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, Egypt., Eldoumani H; Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt., Metwally AS; Department of Pharmacology, Faculty of Veterinary Medicine, Aswan University, Aswan, Egypt., Saleh AA; Department of Animal Wealth Development, Genetics & Genetic Engineering, Faculty of Veterinary Medicine, Zagazig University, Egypt., Mona MM; Department of Medical Biochemistry, Faculty of Medicine, Kafrelsheikh University, Egypt., Abd-Elsalam MM; Department of Histology, Faculty of Medicine, Kafrelsheikh University, Egypt., Hendam BM; Department of Husbandry and Development of Animal Wealth, Genetics & Genetic Engineering, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt., Essawi WM; Department of Theriogenology, Faculty of Veterinary Medicine, Aswan University, Aswan, 81528, Egypt., Abourehab MAS; Department of Pharmaceutics, College of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia., Abdelfattah-Hassan A; Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt; Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Giza, 12578, Egypt. Electronic address: aabdelfattah@vet.zu.edu.eg.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2022 Mar; Vol. 182, pp. 150-159. Date of Electronic Publication: 2022 Feb 24.
DOI: 10.1016/j.freeradbiomed.2022.02.024
Abstrakt: Chronic kidney disease (CKD) is an important global disease its rates are increasing worldwide. CKD is caused by injuries to kidney tissue that exceeds the rate of regeneration, which with time lead to irreversible renal damage and CKD become evident. In females, diminished estrogen supply in the postmenopausal period is associated with greater risk for developing CKD. In this study we isolated exosomes from bone marrow mesenchymal stem/stromal cells (BM-MSCs) and tested their therapeutic effects on post-menopause CKD (PM-CKD) and compared their effects with BM-MSCs. The menopause model was achieved by bilateral ovariectomy in 8-months-old female albino rats, then no treatment, 2 million BM-MSCs or 100 μg of exosomes (Exo) was given intravenously in tail vein to ovariectomized rats and the study continued for 8 weeks post-ovariectomy. Changes in weight, urine volume, urine protein content, kidney function biochemical parameters (creatinine and BUN), Kidney oxidative stress (MDA), kidney antioxidant parameters (SOD, GPx and CAT), histopathological changes, immunohistochemical expression of KIM-1 and, finally, genes related to renal damage (peroxiredoxin-3, KIM-1 and ICAM-1) and inflammation (TNF-α, Cox2 and IL-6) were recorded for all study groups. Post-ovariectomy there was an increased body weight, drastic reduction of estrogen and progesterone levels, reduced urine output, increased urinary protein excretion, elevated serum creatinine and BUN, increased MDA and reduced GPx SOD, and CAT in kidney tissue, chronic inflammation, degenerative and fibrotic lesions in histopathological examination, high expression of KIM-1 immunohistochemically and changes in gene expression analyses all pointing to the development of CKD in the study rats. In the PM-CKD groups receiving BM-MSCs or Exo, the whole chronic inflammatory picture was completely reversed towards a much normal kidney structure and function. The improvements were more observable with Exo compared to BM-MSCs. Overall, our results show for the first time that exosomes isolated from BM-MSCs are more potent in reducing chronic inflammatory changes in the kidney of postmenopausal females compared to the cell-based approach using BM-MSCs. Therefore, MSCs-derived exosomes are a promising therapeutic approach for preserving postmenopausal kidney structure and function and, subsequently, should improve the quality of life of postmenopausal females.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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