Cell Therapy for Ischemic Stroke with Nanoparticle-Labeled 293T Cells and Bone Marrow-Derived Mesenchymal Stem Cells: A Feasibility Study.

Background/

Objectives

Stroke remains the second leading cause of death worldwide, and cell therapy is among the most actively investigated strategies for its treatment. Recent transcriptomic evidence has revealed that 293T cells-the most widely used transient transfection model-possess 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.