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Published on: May 31, 2024
Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models
Ru-Chun Yang1, Xiao-Ling Zhu2, Jun Wang1
1Departmgent of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, People's Republic of China.
Background:
Focal segmental glomerulosclerosis (FSGS) is the most common glomerular etiology of end-stage kidney disease (ESKD). Increasing evidence has indicated the reparative potential of mesenchymal stem cells (MSCs) in damaged diseased kidneys. However, the effect of bone marrow mesenchymal stem cells (BMSCs) on the FSGS progression remains unclear. This study aimed to investigate the protective effects of BMSCs on FSGS progression.
Methods:
A rat model of FSGS was generated via unilateral nephrectomy plus adriamycin injection. Rat BMSCs were isolated and characterized on the basis of their differentiative potential towards adipocytes and osteoblasts and via flow cytometry analysis. Thereafter, rat BMSCs were transplanted into FSGS recipients through the caudal vein. After 8 weeks, 24-h proteinuria, serum creatinine, and urea nitrogen levels were determined. Renal morphology was assessed using a light and transmission electron microscope. MMP9 and TIMP-1 positive cells were detected via immunohistochemical analysis. Expression levels of proinflammatory cytokines IL-6 and TNF-α were examined via RT-PCR.
Results:
The isolated adherent cells from the bone marrow of rats were phenotypically and functionally equivalent to typical MSCs. Clinical examination revealed that BMSC transplantation reduced the 24-h urinary protein excretion, and serum creatinine and urea nitrogen levels. Renal morphology was ameliorated in BMSCs-transplanted rats. Mechanistically, BMSC transplantation significantly downregulated TIMP-1 and upregulated MMP9, thereby increasing the renal MMP9/TIMP-1 ratio. Moreover, BMSC transplantation also downregulated IL-6 and TNF-α.
Conclusions:
BMSC transplantation can attenuate FSGS progression in a rat model of FSGS, thereby providing a theoretical foundation for the application of autologous BMSCs in clinical FSGS therapy.
Insights
Bone marrow mesenchymal stem cells (BMSCs) show protective effects in a rat model of focal segmental glomerulosclerosis (FSGS). BMSC transplantation reduced kidney damage, improving outcomes for FSGS progression.
Area of Science:
- Nephrology
- Regenerative Medicine
- Stem Cell Biology
Background:
- Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage kidney disease.
- Mesenchymal stem cells (MSCs) demonstrate reparative potential in kidney injury.
- The specific impact of bone marrow mesenchymal stem cells (BMSCs) on FSGS progression requires further elucidation.
Purpose of the Study:
- To investigate the protective effects of BMSCs in a rat model of FSGS.
- To determine if BMSC transplantation can attenuate the progression of kidney damage in FSGS.
Main Methods:
- A rat model of FSGS was established using unilateral nephrectomy and adriamycin injection.
- Rat BMSCs were isolated, characterized, and transplanted into FSGS recipients.
- Kidney function (proteinuria, creatinine, urea nitrogen), renal morphology, and molecular markers (MMP9, TIMP-1, IL-6, TNF-α) were assessed post-transplantation.
Main Results:
- BMSC transplantation significantly reduced proteinuria, serum creatinine, and urea nitrogen levels.
- Histological analysis revealed amelioration of renal morphology in BMSC-treated rats.
- BMSC transplantation modulated the MMP9/TIMP-1 ratio and downregulated proinflammatory cytokines (IL-6, TNF-α).
Conclusions:
- BMSC transplantation effectively attenuates FSGS progression in a preclinical rat model.
- These findings provide a theoretical basis for using autologous BMSCs in clinical FSGS therapy.
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