Mesenchymal stem cells prevent podocyte injury in lupus-prone B6.MRL-Faslpr mice via polarizing macrophage into an anti-inflammatory phenotype

Jul 9, 2018Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

Mesenchymal stem cells protect kidney filtering cells in lupus-prone mice by changing immune cells to reduce inflammation

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Abstract

Infusion of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) improved renal pathology in lupus-prone mice.

UC-MSCs increased the expression of podocyte-specific markers, podocin and synaptopodin, in lupus-prone mice.
Treatment with UC-MSCs resulted in reduced deposition of IgG and C3 in the glomeruli.
A decrease in anti-dsDNA antibody levels was observed in UC-MSCs-treated lupus mice.
UC-MSC treatment led to reduced podocyte foot process effacement and less podocyte injury in vitro.
Macrophages treated with UC-MSCs displayed an anti-inflammatory phenotype, showing higher CD206 and lower levels of pro-inflammatory markers.
Lupus mice receiving UC-MSCs exhibited reduced renal macrophage infiltration.

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BACKGROUND: Podocyte injury plays a pathogenic role in the development of lupus nephritis (LN). Mesenchymal stem cells (MSCs) have shown promising therapeutic potential for LN. However, whether MSCs can prevent podocyte injury in LN remains unknown.

METHODS: Human umbilical cord-derived MSCs (UC-MSCs) were infused into lupus-prone B6.MRL-Faslpr (B6.lpr) mice to investigate the influences of UC-MSCs on podocyte injury in LN. Podocytes and macrophages were co-cultured with UC-MSCs in vitro to study the mechanism by which UC-MSC protect podocytes. We further explored the effects of UC-MSCs on macrophage polarization.

RESULTS: We found that UC-MSCs promoted the expression of podocyte-specific markers, podocin and synaptopodin, in lupus-prone B6.lpr mice, along with the improvement of lupus renal pathology in terms of reduced IgG and C3 deposition in glomeruli and decreased anti-dsDNA antibody level. Besides, UC-MSC treatment decreased podocyte foot process effacement, as UC-MSCs-treated macrophages led to less podocyte injury in vitro. Interestingly, we further found that UC-MSCs-treated macrophages exhibited an anti-inflammatory phenotype with higher expression of CD206, and lower expression of tumor necrosis factor-α and interleukin-1β. Additionally, UC-MSCs-treated lupus mice showed reduced renal macrophage infiltration and elevated CD206 expression in kidney.

CONCLUSIONS: Our results demonstrated that UC-MSCs ameliorated LN by preventing podocyte injury possibly through reducing macrophage infiltration and polarizing macrophage into an anti-inflammatory phenotype.

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Mesenchymal stem cells prevent podocyte injury in lupus-prone B6.MRL-Faslpr mice via polarizing macrophage into an anti-inflammatory phenotype

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