Noninvasive in vivo cell tracking using molecular imaging:A useful tool for developing mesenchymal stem cell-based cancer treatment

Mounting evidence has emphasized the potential of cell therapies in treating various diseases by restoring damaged tissues or replacing defective cells in the body.Cell therapies have become a strong therapeutic modality by applying noninvasive in vivo molecular imaging for examining complex cellular processes,understanding pathophysiological mechanisms of diseases,and evaluating the kinetics/dynamics of cell therapies.In particular,mesenchymal stem cells(MSCs)have shown promise in recent years as drug carriers for cancer treatment.They can also be labeled with different probes and tracked in vivo to assess the in vivo effect of administered cells,and to optimize therapy.The exact role of MSCs in oncologic diseases is not clear as MSCs have been shown to be involved in tumor progression and inhibition,and the exact interactions between MSCs and specific cancer microenvironments are not clear.In this review,a multitude of labeling approaches,imaging modalities,and the merits/demerits of each strategy are outlined.In addition,specific examples of the use of MSCs and in vivo imaging in cancer therapy are provided.Finally,present limitations and future outlooks in terms of the translation of different imaging approaches in clinics are discussed.

In vivo bioluminescence imaging of hyperglycemia exacerbating stem cells on choroidal neovascularization in mice

AIM： To investigate the influence of hyperglycemia on the severity of choroidal neovascularization（CNV）,especially the involvement of bone marrow-derived cells（BMCs） and underlying mechanisms.·METHODS： BMCs from firefly luciferase（Fluc）/green fluorescent protein（GFP） double transgenic mice were transplanted into C57BL/6J wide-type mice. The recipient mice were injected intraperitoneally with streptozotocin（STZ） daily for 5 consecutive days to induce diabetes mellitus（DM）, followed by CNV laser photocoagulation.The BMCs recruitment in CNV exposed to hyperglycemia was firstly examined in Fluc/GFP chimeric mice by in vivo optical bioluminescence imaging（BLI） and in vitro Fluc assays. The CNV severity was evaluated by H＆E staining and choroidal flatmount. The expression of vascular endothelial growth factor（VEGF） and stromal cell derived factor-1（SDF-1） was detected by Western blot.·RESULTS： BLI showed that the BMCs exerted dynamic effects in CNV model in Fluc/GFP chimeric mice exposed to hyperglycemia. The signal intensity of transplanted Fluc＋GFP＋BMCs in the DM chimeric mice was significantly higher than that in the control chimeric mice with CNV induction at days 5, 7, 14 and 21（121861.67 ±9948.81 vs 144998.33 ±13787.13 photons/second/cm2/sr for control and DM mice, P5d〈0.05; 178791.67±30350.8 vs240166.67 ±22605.3, P7d〈0.05; 124176.67 ±16253.52 vs196376.67 ±18556.79, P14d〈0.05; 97951.60 ±10343.09 vs119510.00 ±14383.76, P21d〈0.05）, which was consistent with in vitro Fluc assay at day 7 [relative light units of Fluc（RLU1）], 215.00±52.05 vs 707.33±88.65, P 〈0.05; RLU1/relative light units of renilla luciferase（RLU2）, 0.90 ±0.17 vs 1.83 ±0.17, P 〈0.05]. The CNVs in the DM mice were wider than those in the control group at days 5, 7, 14 and21（147.83±17.36 vs 220.33±20.17 μm, P5d〈0.05; 212.17 ±24.63 vs 326.83 ±19.49, P7d〈0.05; 163.17 ±18.24 vs265.17 ±20.55, P14d〈0.05; 132.00 ±10.88 vs 205.33 ±12.98,P21d〈0.05）. The average area of CNV in the DM group was larger at 7d（20688.67±3644.96 vs 32218.00±4132.69 μm2,P 〈0.05）. The expression of VEGF and SDF-1 was enhanced in the DM mice.·CONCLUSION： Hyperglycemia promots the vasculo-genesis of CNV, especially the contribution of BMCs,which might be triggered by VEGF and SDF-1 production.

Molecular imaging of enzyme activity in vivo using activatable probes

Precise measurement of enzyme activity in living systems with molecular imaging probes is becoming an important technique to unravel the functional roles of different enzymes in biological processes. Recent progress has been made in the development of a myriad of molecular imaging probes featuring different imaging modalities, including optical imaging, magnetic resonance imaging, nuclear imaging, and photoacoustic imaging, allowing for non-invasive detection of various enzyme activities in vivo with high sensitivity and high spatial resolution. Among these imaging probes, activatable or ＂smart＂ probes, whose imaging signal can be specifically switched from the ＂off＂ to ＂on＂ state upon interaction with a target enzyme, are particularly attractive due to their improved sensitivity and specificity. Here, recent advances in the development of activatable probes capable of imaging different enzyme activities in vivo are summarized based on different imaging modalities, and current challenges and future perspectives are discussed.

A DR-WFOI fusion system for the real-time molecular imaging in vivo

Digital radiography （DR） and whole-body fluorescent optical imaging （WFOI） have been widely applied in the field of molecular imaging, with the advantages in tissues and functional imaging. The integration of them contributes to the development and discovery of medicine. We introduce an equipment, performance of which is better than that of another molecular imaging system manufactured by Kodak Corp. It can take real-time small animal imaging in vivo, with lower cost and shorter development cycle on the LabVIEW platform. At last, a paradigm experiment on a nude mouse with green fluorescent protein （GFP） transgenic tumor is given to present a real-time DR-WFOI fusion simultaneous image.