An NIR‐II Fluorescence/Dual Bioluminescence Multiplexed Imaging for In Vivo Visualizing the Location, Survival, and Differentiation of Transplanted Stem Cells

Abstract

The in vivo distribution, viability, and differentiation capability of transplanted stem cells are vital for the therapeutic efficacy of stem cell-based therapy. Herein, an NIR-II fluorescence/dual bioluminescence multiplexed imaging method covering the visible and the second near-infrared window from 400 to 1700 nm is successfully developed for in vivo monitoring the location, survival, and osteogenic differentiation of transplanted human mesenchymal stem cells (hMSCs) in a calvarial defect mouse model. The exogenous Ag 2 S quantum dot-based fluorescence imaging in the second near-infrared window is applied for visualizing the long-term biodistribution of transplanted hMSCs. Endogenous red firefly luciferase (RFLuc)-based bioluminescence imaging (BLI) and the collagen type 1 promoter-driven Gaussia luciferase (GLuc)based BLI are employed to report the survival and osteogenic differentiation statuses of the transplanted hMSCs. Meanwhile, by integrating the three imaging channels, multiple dynamic biological behaviors of transplanted hMSCs and the promotion effects of immunosuppression and the bone morphogenetic protein 2 on the survival and osteogenic differentiation of transplanted hMSCs are directly observed. The novel multiplexed imaging method can greatly expand the capability for multifunctional analysis of the fates and therapeutic capabilities of the transplanted stem cells, and aid in the improvement of stem cell-based regeneration therapies and their clinical translation.

Recent Progress of Hybrid Optical Probes for Neural Membrane Potential Imaging

“…[6] However, the strong interaction between visible light and tissues (such as absorption and scattering) raises several limitations, such as the shallow tissue penetration depth, phototoxicity, and high autofluorescence. NIR light (650-1700 nm), [64][65][66] particularly the NIR-II light (1000-1700 nm), [67,68] has been proved to be more promising for in vivo imaging with high tissue penetration depth, low phototoxicity, and excellent SNR due to its lower energy and longer wavelength than visible light. However, membrane potential imaging in the NIR range beyond 900 nm has not been achieved yet.…”

Sandwich-Type Near-Infrared Conjugated Polymer Nanoparticles for Revealing the Fate of Transplanted Human Umbilical Cord Mesenchymal Stem Cells

“…Delightfully, no significant decrease of NIR fluorescence intensity was found even up to 20 days after subcutaneous transplantation, comparable to quantum dot-based fluorescence dyes. 37,46,47 Excellent physical stability was also observed even after storage for 10 weeks in air at temperatures of 4 and 37 °C or in a biological environment (Figure 2E). The negligible increase of size in both PBS and α-MEM + 10% FBS is likely due to the charge neutralization of surface silanol groups by ionic species and rapid adsorption of proteins on the CPN surface.…”

Quantum dots for bone tissue engineering

“…By binding to the red firefly luciferase (RFLuc) and Gaussia luciferase (GLuc) reporter genes, Ag 2 S QDs not only labeled hMSCs, but also effectively indicated their survival status and osteogenic differentiation process. In addition, the study also found that immunosuppression and the use of BMP-2 can significantly improve the survival rate and osteogenic differentiation ability of hMSCs, further confirming the application potential of QDs in promoting tissue regeneration and improving the effectiveness of stem cell therapy [ 119 ]. Clinical trials using fluorescent nanoparticles have begun in the United States [ 120 ].…”