article · Biomolecules
Chronic kidney disease is an escalating global issue, and the reduction of oestrogen following menopause represents a notable risk factor for females. An experimental evaluation assessed whether extracellular vesicles, specifically exosomes derived from bone marrow mesenchymal stem cells, could counter chronic kidney damage in a surgical menopause model using female albino rats. Ovariectomised rats experienced typical indicators of kidney injury, including reduced urine output, heightened protein excretion, elevated blood urea nitrogen and creatinine, oxidative stress, and tissue fibrosis. Administering bone marrow mesenchymal stem cell exosomes over two months restored antioxidant enzyme levels, reduced markers of cell death and fibrosis, and corrected chronic inflammatory damage to achieve near-normal kidney architecture and function. These findings highlight the potential of stem cell-derived exosomes to alleviate post-menopausal renal damage by countering fibrosis and apoptotic pathways.
Post-menopausal women face an elevated risk of developing chronic kidney disease due to hormonal decline, yet targeted therapies remain scarce. Demonstrating that stem cell-derived exosomes can reverse renal inflammation, fibrosis, and cell death offers a promising biological approach to safeguarding kidney health and enhancing quality of life for females experiencing menopause.
This research represents early-stage preclinical work evaluating cell-free therapies for post-menopausal renal disease. Potential applications lie in developing targeted biotherapeutics for healthcare providers in nephrology and women's health. Because testing has only been conducted in an animal model over a two-month period, substantial clinical development, safety verification, and biomanufacturing scale-up are required before any real-world human therapeutic deployment can occur.
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The rate of chronic kidney disease (CKD) is increasing globally, and it is caused by continuous damage to kidney tissue. With time the renal damage becomes irreversible, leading to CKD development. In females, post-menopause lack of estrogen supply has been described as a risk factor for CKD development, and studies targeting post-menopause CKD are scarce. In the present study, we used exosomes isolated from bone marrow mesenchymal stem/stromal cells (BM-MSCs) to test their therapeutic potential against the development of CKD. At first, the menopause model was achieved by surgical bilateral ovariectomy in female albino rats. After that, 100 µg of exosomes was given to ovariectomized rats, and the study continued for 2 months. Changes in urine volume, urine protein content, kidney function biochemical parameters (creatinine and BUN), kidney antioxidant parameters (SOD, GPx and CAT), histological changes, immunohistochemical levels of caspase 3, and the gene expression of NGAL (related to kidney damage), TGFβ1 and αSMA (related to fibrosis and EMT), and caspase 3 (related to apoptosis) were studied. After the ovariectomy, the occurrence of CKD was confirmed in the rats by the drastic reduction of serum estrogen and progesterone levels, reduced urine output, increased urinary protein excretion, elevated serum creatinine and BUN, reduced GPx SOD, and CAT in kidney tissue, degenerative and fibrotic lesions in the histopathological examination, higher immunohistochemical expression of caspase 3 and increased expression of all studied genes. After exosomes administration, the entire chronic inflammatory picture in the kidney was corrected, and a near-normal kidney structure and function were attained. This study shows for the first time that BM-MSCs exosomes are potent for reducing apoptosis and fibrosis levels and, thus, can reduce the chronic damage of the kidneys in females that are in their menopause period. Therefore, MSCs-derived exosomes should be considered a valuable therapy for preserving postmenopausal kidney structure and function and, subsequently, could improve the quality of females' life during menopause.
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DOI: 10.3390/biom12050663
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