Muse Cells Orchestrating Renal Repair via Macrophage M2 Polarization in Ischemia-Reperfusion Injury

Acute renal ischemia-reperfusion injury (IRI) poses significant challenges in clinical management, necessitating the exploration of novel therapeutic strategies. This study investigates the therapeutic potential and underlying mechanisms of multilineage-differentiating stress-enduring (Muse) cells in alleviating renal IRI. In recent years, stem cell research has advanced significantly, providing promising prospects for clinical treatment. Mesenchymal stromal cells (MSCs), from which Muse cells are derived, are a heterogeneous population of cells that include stem cells with varying degrees of multipotency, committed progenitors, and differentiated cells. Muse cells, a subpopulation of MSCs, were isolated from adipose tissue obtained through liposuction in this study. In vivo studies revealed the effective recruitment of Muse cells to injured kidneys and their ability to ameliorate renal pathological damage and improve renal function in a rat model of acute kidney IRI. Mechanistically, Muse cells modulated the polarization of macrophages toward an anti-inflammatory M2 phenotype, as evidenced by decreased M1/M2 ratios. In vitro experiments further elucidated the interaction between Muse cells and macrophages, demonstrating Muse cell-mediated promotion of M2 polarization. Co-culture with M2 macrophages during reoxygenation phases enhanced the survival of renal tubular epithelial cells following hypoxia-reoxygenation injury, highlighting the therapeutic potential of Muse cells in mitigating renal IRI through modulation of macrophage polarization. These findings provide insights into the therapeutic mechanisms of Muse cells and offer promising avenues for the development of innovative renal injury treatments.