In Vivo Tracking Of Transplanted Mesenchymal Stem Cells Using The Near-infrared Ag2S QDs

Mesenchymal stem cells (MSCs) have shown great potential for tissue repair andregeneration. However, the homing behavior and accurate location of transplantedMSCs in response to tissue injury are still poorly determined. In this work, fluorescenceimaging in the second near-infrared (NIR-II) window using Ag2S quantum dots (QDs)was performed to determine the dynamic homing behavior of transplanted humanmesenchymal stem cells (hMSCs) in mice. In order to image the transplanted hMSCs invivo, Ag2S QDs were firstly conjugated with Tat peptide as the targeting ligand tohMSCs. it was found that Tat-Ag2S QDs can label hMSCs effectively without causingof ROS production, apoptosis/necrosis and DNA damage in hMSCs or affecting theproliferation, differentiation and stem gene expression of hMSCs grown both ontwo-dimensional plate and three-dimensional collagen scaffold. These results indicatedthe high biocompatibility of Tat-Ag2S QDs for hMSCs labeling. Because of thenegligible autofluorescence of live tissues in the NIR-II region, as few as1000cells areable to be detected for in vivo imaging, which is a significant improvement fromtraditional QDs-based cell tracking techniques in the visible and NIR-I region.Moreover, the location of subcutaneously transplanted collagen-grown hMSCs can bemonitored up to60days by Ag2S QDs without affecting the survival, mobility anddifferentiation of hMSCs, indicating the great potential of Ag2S QDs in long-term stemcell tracking. Benefit from the excellent biocompatibility and desirable resolution ofAg2S QDs-based NIR-II imaging, for the first time, it was found that hMSCs wererecruited at the wound sites and predominantly accumulated around the edge of woundafter intravenously injection. The failure of recruiting cells and beneficial factors fortissue regeneration in the middle of wound may result in the poor healing of fullthickness skin wounds. For wounds treated with stromal cell derived factor-1α(SDF-1α)-loaded collagen scaffolds, more hMSCs were recruited at the wound sites within a much shorter time, and hMSCs were distributed relatively homogenous acrossthe whole wound area. Thus, the accelerated wound closure, enhancedre-epithelialization and neovascularization for the wound treated with SDF-1α-loadedcollagen scaffolds were achieved. The in vivo NIR-II imaging offers the first-handknowledge of the homing behavior of MSCs in response to cutaneous tissue injury, anddirect evidences of the SDF-1α-loaded collagen scaffolds for tissue regeneration. Ourresults highlight the promise of Ag2S QDs as a NIR-II nanoprobe for long-term,noninvasive, in vivo stem cell tracking with both high sensitivity and elevated spatialand temporal resolution, and encourage further clinical applications in imaging-guidedcell therapies.