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Here, a vitality\u2010enhanced dual\u2010modal tracking system is designed to improve engraftment efficiency and is utilized to noninvasively explore the fate of intravenous transplanted human umbilical cord\u2010derived MSCs during long\u2010term treatment of ischemic stroke. Such a system is obtained by bioorthogonally conjugating magnetic resonance imaging (MRI) contrast and near\u2010infrared fluorescence (NIRF) imaging nanoparticles to metabolic glycoengineered MSCs with a lipoic acid\u2010containing extracellular antioxidative protective layer. The dynamic fates of MSCs in multi\u2010dimensional space\u2010time evolution are digitally detailed for up to 28 days using MRI and NIRF imaging equipment, and the protective layer greatly shields MSCs from reactive oxygen spices (ROS) degradation, enhances MSC survival, and engraftment efficiency. Additionally, it is observed that the bioengineered MSCs exhibit dynamic intelligent responses corresponding to microenvironment remodeling and exert enhanced therapeutic effects. This dual\u2010modal tracking system enables long\u2010term tracking of MSCs while improving their viability at the lesion sites, which may serve as a valuable tool for expediting the clinical translation of MSC therapy.<\/jats:p>","DOI":"10.1002\/smll.202203431","type":"journal-article","created":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T02:46:11Z","timestamp":1664592371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Vitality\u2010Enhanced Dual\u2010Modal Tracking System Reveals the Dynamic Fate of Mesenchymal Stem Cells for Stroke Therapy"],"prefix":"10.1002","volume":"18","author":[{"given":"Jianpei","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy &amp; Shanghai Pudong Hospital Key Laboratory of Smart Drug Delivery Ministry of Education Fudan University  826 Zhangheng Road Shanghai 201203 P. R. 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