Abstract: TH-PO079
Single-Cell Dissection of Cellular and Molecular Features Underlying Mesenchymal Stem Cell Therapy in Ischemic AKI
Session Information
- AKI: Mechanisms - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Wang, Wenjuan, Nankai University School of Medicine, Tianjin, Tianjin, China
- Zhang, Min, First Medical Center of Chinese PLA General Hospital Nephrology Institute of the Chinese People's Liberation Army, Beijing, Beijing, China
- Chen, Xiangmei, First Medical Center of Chinese PLA General Hospital Nephrology Institute of the Chinese People's Liberation Army, Beijing, Beijing, China
- Cai, Guangyan, First Medical Center of Chinese PLA General Hospital Nephrology Institute of the Chinese People's Liberation Army, Beijing, Beijing, China
Background
Mesenchymal stem cells (MSCs) exert beneficial therapeutic effects in acute kidney injury (AKI), while the detailed repair mechanism remains unclear.
Methods
Single cell sequencing was used for the first time to delineate the mechanism of MSC treatment for AKI induced by bilateral ischemia reperfusion injury in C57 mice. Receptor-ligand interaction analysis focused on the elucidation of intercellular communication. Extracellular vesicles (EVs) derived from MSCs were extracted by ultracentrifugation combined with size exclusion chromatography. Transmission electron microscopy, nanoparticle tracking analysis, cell transfection, flow cytometry, RT-qPCR, Western blot, and immunohistochemistry were used to evaluate cellular function.
Results
Our analyses uncovered renal tubular epithelial cells (TECs) and immune cells transcriptomic diversity and highlighted a repair trajectory involving renal stem/progenitor cell differentiation. Our findings also suggested pro-fibrotic factors such as ZEB2 and PDGFβ expressed by TECs promoted the recruitment of inflammatory monocytes and Th17 cells to injured kidney tissue, inducing TGF-β1 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 in mediating the therapeutic effects of MSCs by inhibiting Zeb2 expression and suppressing pro-fibrotic TECs and its subsequent recruitment of immune cell subpopulations.
Conclusion
Exogenous MSCs promote the potential repair trajectories involving renal stem/progenitor epithelial differentiation and the inhibition of the miR-26a/Zeb2 pathway on immune cells infiltration and fibrosis in response to MSC therapy during AKI-CKD progression, which helps to optimize future AKI treatment.
Summary of the role of MSCs in the regulation of kidney repair and fibrosis during AKI-CKD progression.
Funding
- Government Support – Non-U.S.