Abstract
Stem cell therapy holds high promises in regenerative medicine. The major challenge of clinical translation is to precisely and quantitatively evaluate the in vivo cell distribution, migration, and engraftment, which cannot be easily achieved by current techniques. To address this issue, for the first time, we have developed a molecular cell tracker with a strong fluorescence signal in the second near-infrared (NIR-II) window (1,000-1,700 nm) for real-time monitoring of in vivo cell behaviors in both healthy and diseased animal models. The NIR-II tracker (CelTrac1000) has shown complete cell labeling with low cytotoxicity and profound long-term tracking ability for 30 days in high spatiotemporal resolution for semiquantification of the biodistribution of transplanted stem cells. Taking advantage of the unique merits of CelTrac1000, the responses of transplanted stem cells to different diseased environments have been discriminated and unveiled. Furthermore, we also demonstrate CelTrac1000 as a universal and effective technique for ultrafast real-time tracking of the cellular migration and distribution in a 100 μm single-cell cluster spatial resolution, along with the lung contraction and heart beating. As such, this NIR-II tracker will shift the optical cell tracking into a single-cell cluster and millisecond temporal resolution for better evaluating and understanding stem cell therapy, affording optimal doses and efficacy.
Highlights
Stem cells are pluripotent cells with self-renewing capacity, which can differentiate into a range of cell types under defined circumstances [1,2,3]
The probe was analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS), suggesting it is a single molecule with a molar ratio of CH-4T : human serum albumin (HSA) : Tat at 1 : 1 : 1 (Figures S1-3 in Supplementary Information)
We further examined the optical properties of CelTrac1000 in aqueous solution, showing absorption and emission peaks at 750 and 1,000 nm, respectively (Figure 1(b))
Summary
Stem cells are pluripotent cells with self-renewing capacity, which can differentiate into a range of cell types under defined circumstances [1,2,3]. Stem cell therapy was on track for approval for human use in Japan for damaged corneas [10,11,12,13,14,15,16,17]. One roadblock preventing further widespread applications of stem cell therapy is the difficulty in tracking cell fates upon transplantation, preventing early assessment of dosage, retention, and therapeutic efficacy. Addressing this issue would greatly benefit the prognosis and overall outcomes [18]. It is of great significance to track stem cells both in vitro and in vivo with
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