Noninvasive Monitoring of the Mitochondrial Function in Mesenchymal Stromal Cells

Purpose: Mitochondria are a gatekeeper of cell survival and mitochondrial function can be used to monitor cell stress. Here we validate a pathway-specific reporter gene to noninvasively image the mitochondrial function of stem cells. Procedures: We constructed a mitochondrial sensor with the firefly luciferase (Fluc) reporter gene driven by the NQO1 enzyme promoter. The sensor was introduced in stem cells and validated in vitro and in vivo, in a mouse model of myocardial ischemia/reperfusion (IR). Results: The sensor activity showed an inverse relationship with mitochondrial function (R² = −0.975, p = 0.025) and showed specificity and sensitivity for mitochondrial dysfunction. In vivo, NQO1-Fluc activity was significantly higher in IR animals vs. controls, indicative of mitochondrial dysfunction, and was corroborated by ex vivo luminometry. Conclusions: Reporter gene imaging allows assessment of the biology of transplanted mesenchymal stromal cells (MSCs), providing important information that can be used to improve the phenotype and survival of transplanted stem cells.