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Exosomes derived from human umbilical cord mesenchymal stem cells attenuate kidney inflammation in a 5/6 subtotal
Z Z Nurfatihah1, D C R Sari1, R Yuniartha1
1Universitas Gadjah Mada, Faculty of Medicine, Public Health, and Nursing, Department of Anatomy, Yogyakarta, Indonesia.
Insights
Mesenchymal stem cell-derived exosomes show potential in treating chronic kidney disease by reducing kidney inflammation and fibrosis. This study demonstrates their ability to inhibit inflammatory gene expression and macrophage infiltration in a rat model.
Area of Science:
- Nephrology
- Regenerative Medicine
- Biotechnology
Background:
- Chronic kidney disease (CKD) is a significant global health issue, often caused by kidney fibrosis and chronic inflammation.
- Current treatments like dialysis and transplantation have limitations.
- Mesenchymal stem cells (MSCs) and their secreted exosomes offer promising therapeutic potential for kidney repair.
Purpose of the Study:
- To investigate the anti-inflammatory and anti-fibrotic effects of exosomes derived from MSCs in a rat model of CKD.
- To evaluate the impact of exosome treatment on key inflammatory markers and cellular infiltration in kidney tissue.
Main Methods:
- A 5/6 subtotal nephrectomy (SN) rat model was established.
- Rats were divided into sham operation, SN, and SN with varying doses of exosome treatment groups.
- Kidney tissue was analyzed for mRNA expression of NF-κB and MCP-1 using RT-PCR and for macrophage infiltration via immunohistochemistry (IHC).
Main Results:
- Exosome treatment significantly reduced NF-κB mRNA expression in SN rats compared to controls.
- While MCP-1 mRNA levels did not significantly differ, exosome treatment notably decreased macrophage infiltration in kidney tissue.
- These findings suggest a dose-dependent inhibitory effect of exosomes on inflammatory markers.
Conclusions:
- Exosomes derived from MSCs demonstrate a potential therapeutic effect in mitigating kidney inflammation.
- Exosome treatment effectively inhibited inflammatory gene expression and reduced macrophage infiltration in a rat model of kidney injury.
- MSC-derived exosomes represent a promising, safer alternative for managing CKD progression.
Introduction:
Chronic kidney disease (CKD) is a noncommunicable disease that contributes to the rise of global mortality rate. The condition is marked by reduced kidney function persisting for three months or longer. The main cause of CKD is kidney fibrosis, resulting from chronic inflammation. Current CKD therapies, such as hemodialysis and kidney transplants, are limited in effectiveness. Stem cell-derived therapy, particularly mesenchymal stem cells (MSC), provide great potential for reducing inflammation and fibrosis. Notably, exosomes secreted by MSC offer a safer and more effective alternative by carrying bioactive molecules that can repair kidney function through modulating inflammatory processes.
Materials And Methods:
Twenty-five male 3-month-old Wistar rat were divided into five groups: Sham operation (SO, n=5), 5/6 subtotal nephrectomy (SN, n=5), SN with exosome treatment at total protein concentration of 48.30 μg (SNE1, n=5), 96.61 μg (SNE2, n=5), and 193.21 μg (SNE3, n=5). The rat was euthanized, and the kidneys were harvested for analysis. The mRNA expression levels of NF-κB and MCP-1 were measured using RT-PCR. Macrophage infiltration was assessed using immunohistochemistry (IHC) staining with anti-CD68 antibodies.
Results:
The mRNA expression of NF-κB was significantly higher in the SN group compared to the SO group. In the exosome groups (SNE1, SNE2, and SNE3), NF-κB expression was significantly lower than in the SN group (p = 0.011, 0.029, 0.026, respectively). The mRNA expression of MCP-1 in the exosome groups was not significantly different from the SN group. IHC staining showed the SN group had a more dominant macrophage infiltration compared to the SO group. The exosome group exhibited a less dominant macrophage infiltration compared to the SN group.
Conclusion:
Exosomes may attenuate kidney inflammation by inhibiting inflammatory gene expression and macrophage infiltration in a 5/6 subtotal nephrectomy rat model.
