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.
Stem cell-based regenerative medicine has attracted tremendous attention for its great potential to treat numerous incurable diseases. Tracking and understanding the fate and regenerative capabilities of transplanted stem cells is vital for improving the safety and therapeutic efficacy of stem cell-based therapy, therefore accelerating the clinical application of stem cells. Fluorescent nanoparticles (NPs) have been widely used for in vivo tracking of the transplanted stem cells. Among these fluorescent NPs, near-infrared (NIR) NPs have greatly improved the sensitivity, tissue penetration depth, spatial and temporal resolutions of the fluorescence imaging-based stem cell tracking technologies due to the reduced absorption, scattering, and autofluorescence of NIR fluorescence in tissues. Here, this review summarizes the recent studies regarding the tracking of transplanted stem cells using NIR NPs and emphasizes the recent advances of fluorescence imaging in the second NIR window (NIR-II, 1000-1700 nm). Furthermore, the challenges and future prospects of the NIR NP-based technologies are also discussed.
Effective drug delivery in the central nervous system (CNS) needs to have long blood-circulation halflives, to pass through the blood−brain barrier (BBB), and subsequently to be taken up by target cells. Herein, a traceable CNS delivery nanoformulation (RVG-NV-NPs) is developed by encapsulating bexarotene (Bex) and AgAuSe quantum dots (QDs) within Lamp2b-RVG-overexpressed neural stem cell (NSC) membranes. The highfidelity near-infrared-II imaging by AgAuSe QDs offers a possibility of in vivo monitoring the multiscale delivery process of the nanoformulation from the whole-body to the single-cell scale. It was revealed the synergy of acetylcholine receptor-targeting of RVG and the natural brain-homing and low immunogenicity of NSC membranes prolong the blood circulation, facilitate BBB crossing and nerve cell targeting of RVG-NV-NPs. Thus, in Alzheimer's disease (AD) mice, the intravenous delivery of as low as 0.5% of oral dose Bex showed highly effective up-regulation of the apolipoprotein E expression, resulting rapid alleviation of ∼40% β-amyloid (Aβ) level in the brain interstitial fluid after a single dose administration. The pathological progression of Aβ in AD mice is completely suppressed during a 1 month treatment, thus effectively protecting neurons from Aβ-induced apoptosis and maintaining the cognitive abilities of AD mice.
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