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The effect of mesenchymal stromal cells on doxorubicin-induced nephropathy in rats
Hualin Ma1, Yaojiong Wu, Wanfan Zhang
1Department of Nephrology, Shenzhen People's Hospital, Second Clinical Medical College, Jinan University, Shenzhen, China.
Background Aims:
The potential protective effects of mesenchymal stromal cells (MSCs) on some kidney diseases has been reported. However, the effect of MSCs on doxorubicin-induced nephropathy is still poorly understood.
Methods:
Rats with doxorubicin-induced kidney injuries were treated with human cord-derived MSCs. Human MSCs were first labeled with 5-bromo-2'-deoxyuridine to track their homing in kidneys after infusion.
Results:
Alleviation of proteinuria, decreased serum albumin, alleviation of lipid disorders and histologic alterations were found in rats 4 weeks after treatment with MSCs, particularly in rats that were given repeat doses. Decreases in serum levels of interleukin-6, tumor necrosis factor-α and prostaglandin E2 and decreases in messenger RNA levels of kidney tissue cylooxygenase-2 and EP4 were found in MSC-treated rats. MSC-treated rats also displayed an increase in serum interleukin-10 levels.
Conclusions:
These results indicate that MSCs ameliorate doxorubicin-induced kidney injuries and inflammation, suggesting a potential clinical treatment for inflammatory kidney diseases.
Insights
Mesenchymal stromal cells (MSCs) show promise in treating doxorubicin-induced kidney injury by reducing inflammation and improving kidney function. These findings suggest MSCs could be a novel therapy for inflammatory kidney diseases.
Area of Science:
- Regenerative Medicine
- Nephrology
- Immunology
Background:
- Mesenchymal stromal cells (MSCs) have demonstrated protective effects in various kidney diseases.
- The therapeutic potential of MSCs in doxorubicin-induced nephropathy remains largely unexplored.
Purpose of the Study:
- To investigate the efficacy of human cord-derived MSCs in ameliorating doxorubicin-induced kidney injury in a rat model.
- To elucidate the underlying mechanisms of MSCs' protective effects on kidney inflammation.
Main Methods:
- Rats were induced with kidney injury using doxorubicin and subsequently treated with human cord-derived MSCs.
- MSCs were labeled with 5-bromo-2'-deoxyuridine for tracking homing in renal tissues post-infusion.
Main Results:
- MSC treatment led to alleviation of proteinuria, hypoalbuminemia, and lipid disorders, with improved histology.
- Significant reductions in pro-inflammatory markers (IL-6, TNF-α, PGE2, COX-2 mRNA) and an increase in anti-inflammatory IL-10 were observed.
- Repeat dosing of MSCs enhanced the observed therapeutic benefits.
Conclusions:
- MSCs effectively ameliorate doxorubicin-induced kidney injury and associated inflammation.
- The findings support MSCs as a potential therapeutic strategy for inflammatory kidney diseases.
