| First Author | Zhang K | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 34 | Pages | 12203-12213 |
| PubMed ID | 32641493 | Mgi Jnum | J:299147 |
| Mgi Id | MGI:6477875 | Doi | 10.1074/jbc.RA120.012732 |
| Citation | Zhang K, et al. (2020) In vivo two-photon microscopy reveals the contribution of Sox9(+) cell to kidney regeneration in a mouse model with extracellular vesicle treatment. J Biol Chem 295(34):12203-12213 |
| abstractText | Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been shown to stimulate regeneration in the treatment of kidney injury. Renal regeneration is also thought to be stimulated by the activation of Sox9(+) cells. However, whether and how the activation mechanisms underlying EV treatment and Sox9(+) cell-dependent regeneration intersect is unclear. We reasoned that a high-resolution imaging platform in living animals could help to untangle this system. To test this idea, we first applied EVs derived from human placenta-derived MSCs (hP-MSCs) to a Sox9-Cre(ERT2); R26(mTmG) transgenic mouse model of acute kidney injury (AKI). Then, we developed an abdominal imaging window in the mouse and tracked the Sox9(+) cells in the inducible Sox9-Cre transgenic mice via in vivo lineage tracing with two-photon intravital microscopy. Our results demonstrated that EVs can travel to the injured kidneys post intravenous injection as visualized by Gaussia luciferase imaging and markedly increase the activation of Sox9(+) cells. Moreover, the two-photon living imaging of lineage-labeled Sox9(+) cells showed that the EVs promoted the expansion of Sox9(+) cells in kidneys post AKI. Histological staining results confirmed that the descendants of Sox9(+) cells contributed to nephric tubule regeneration which significantly ameliorated the renal function after AKI. In summary, intravital lineage tracing with two-photon microscopy through an embedded abdominal imaging window provides a practical strategy to investigate the beneficial functions and to clarify the mechanisms of regenerative therapies in AKI. |
