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Published on: February 15, 2022
Mesenchymal stem cells ameliorate sepsis-associated acute kidney injury in mice
Cong-juan Luo1, Fu-jian Zhang, Li Zhang
1State Key Laboratory of Kidney Diseases, Department of Nephrology, Chinese PLA General Hospital and Medical School of Chinese PLA, Beijing, People's Republic of China.
Objective:
Significant progress has been made in critical care medicine during the past several decades. However, the mortality rate is still high in patients with sepsis, especially with acute kidney injury (AKI). Mesenchymal stem cells (MSCs) possess an ability to ameliorate renal injury from ischemia-reperfusion, but it is still unknown whether they have the ability to reduce sepsis-associated AKI.
Methods:
Male C57BL/6 mice underwent cecal ligation and puncture operation to induce sepsis and then received either normal saline or MSCs (1 × 10 cells intravenously) 3 h after surgery.
Results:
Within 24 h after cecal ligation and puncture operation, the septic mice developed kidney injury and exhibited a higher mortality. Treatment with MSCs decreased serum creatinine and blood urea nitrogen levels and improved recovery of tubular function. mRNA levels of interleukin 6 (IL-6), IL-17, tumor necrosis factor α, interferon γ, CXCL1, CXCL2, CXCL5, CCL2, and CCL3 in kidney tissue were dramatically decreased after MSC treatment. Neutrophil infiltration in kidney and blood bacterial loads were attenuated after MSC injection. Moreover, mice treated with MSCs had a higher survival rate than the saline treatment group. Injected MSCs were mainly localized in the lungs, spleen, and abdominal cavity lymph node, but not in the kidneys.
Conclusions:
Treatment with MSCs can alleviate sepsis-associated AKI and improve survival in mice with polymicrobial sepsis. These effects may be mediated by the inhibition of IL-17 secretion and balance of the proinflammatory and anti-inflammatory states. Mesenchymal stem cells may be a potential new therapeutic agent for the prevention or reduction of sepsis-associated AKI.
Insights
Mesenchymal stem cells (MSCs) treatment significantly reduced sepsis-associated acute kidney injury (AKI) and improved survival in mice. MSCs alleviated kidney damage by reducing inflammation and bacterial load, offering a potential therapeutic strategy for sepsis-induced AKI.
Area of Science:
- Critical Care Medicine
- Nephrology
- Regenerative Medicine
Background:
- Sepsis remains a leading cause of mortality, particularly when complicated by acute kidney injury (AKI).
- Mesenchymal stem cells (MSCs) show promise in treating ischemia-reperfusion injury, but their efficacy in sepsis-associated AKI is unclear.
Purpose of the Study:
- To investigate the therapeutic potential of MSCs in reducing sepsis-associated AKI and improving survival.
- To elucidate the mechanisms underlying MSCs' effects on sepsis-induced kidney damage.
Main Methods:
- Male C57BL/6 mice underwent cecal ligation and puncture to induce polymicrobial sepsis.
- Mesenchymal stem cells (MSCs) were administered intravenously 3 hours post-surgery.
Main Results:
- MSC treatment significantly decreased serum creatinine and blood urea nitrogen levels, improving tubular function recovery.
- MSC administration reduced pro-inflammatory cytokine mRNA levels (IL-6, IL-17, TNF-α, IFN-γ) and neutrophil infiltration in the kidneys.
- Mice treated with MSCs exhibited increased survival rates, attenuated blood bacterial loads, and reduced kidney injury markers.
Conclusions:
- Mesenchymal stem cells (MSCs) effectively alleviate sepsis-associated AKI and enhance survival in a murine model.
- The protective effects of MSCs are likely mediated by the inhibition of IL-17 and the rebalancing of pro- and anti-inflammatory states.
- MSCs represent a promising therapeutic candidate for preventing or mitigating sepsis-induced AKI.
