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Recent transcriptomic evidence has revealed that 293T cells\u2014the most widely used transient transfection model\u2014possess a neural crest\/neuronal lineage, making them a candidate for acute neural tissue engineering. Methods: We implanted iron oxide nanoparticle-labeled 293T cells (293T-ION) into an ischemic rat brain and monitored them longitudinally by 7T MRI, using ION-labeled bone marrow-derived mesenchymal stem cells (rMSC-ION) as a direct comparison. Functional recovery was assessed via mNSS and corner test scores, and infarct size was quantified by MRI. Results: 293T-ION cells showed no migration throughout the 40-day observation period, and functional recovery plateaued early compared with the progressive improvement seen with rMSC-ION. 293T cell implantation provoked pronounced, localized CD68-positive microglial hyperactivation at both implantation and ischemic sites, without migration toward the choroid plexus (CP). In contrast, rMSC-ION actively migrated to the CP and drove superior neuroplasticity marker expression (Ki67, Nestin, NeuN). Conclusions: 293T cells produce transient localized microglial activation and limited brain plasticity, whereas rMSCs drive sustained neurorestoration. Synergistic co-administration of these cell types may represent a future therapeutic strategy bridging hyper-acute and chronic recovery phases.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060704","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:43:54Z","timestamp":1780965834000},"page":"704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell Therapy for Ischemic Stroke with Nanoparticle-Labeled 293T Cells and Bone Marrow-Derived Mesenchymal Stem Cells: A Feasibility Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8242-1690","authenticated-orcid":false,"given":"Kuo-Feng","family":"Huang","sequence":"first","affiliation":[{"name":"Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Te-Sun","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Taipei Tzu-Chi Hospital, Buddhist Tzu-Chi Medical Foundation, New Taipei City 23142, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5249-1679","authenticated-orcid":false,"given":"Jong-Kai","family":"Hsiao","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Department of Medical Imaging, Taipei Tzu-Chi Hospital, Buddhist Tzu-Chi Medical Foundation, New Taipei City 23142, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41572-019-0118-8","article-title":"Ischaemic stroke","volume":"5","author":"Campbell","year":"2019","journal-title":"Nat. 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