Single-cell dissection of cellular and molecular features underlying mesenchymal stem cell therapy in ischemic acute kidney injury

Mesenchymal stem cells (MSCs) exert beneficial therapeutic effects in acute kidney injury (AKI), while the detailed repair mechanism remains unclear. Herein, we probed the underlying mechanisms of MSC therapy in AKI by performing unbiased single-cell RNA sequencing in IRI model with/without MSC treatment. Our analyses uncovered the tubular epithelial cells (TECs) and immune cells transcriptomic diversity and highlighted a repair trajectory involving renal stem/progenitor cell differentiation. Our findings also suggested that profibrotic TECs expressing pro-fibrotic factors such as Zeb2 and Pdgfb promoted the recruitment of inflammatory monocytes and Th17 cells to injured kidney tissue, inducing TGF-b1 secretion and renal fibrosis. Finally, in addition to activating the repair properties of renal progenitor/stem cells, we uncovered a role for MSC-derived miR-26a-5p in mediating the therapeutic effects of MSCs by inhibiting Zeb2 expression and suppressing pro-fibrotic TECs and its subsequent recruitment of immune cell subpopulations. These findings may help to optimize future AKI treatment strategies.

Automated summary

This study investigated the therapeutic mechanisms of mesenchymal stem cells (MSCs) in acute kidney injury (AKI) using unbiased single-cell RNA sequencing. The research revealed the transcriptomic diversity of tubular epithelial cells (TECs) and immune cells, and identified a repair trajectory involving renal stem/progenitor cell differentiation. The study also found that MSC-derived miR-26a-5p played a role in mediating the therapeutic effects of MSCs by inhibiting the expression of pro-fibrotic TECs and the recruitment of immune cell subpopulations.