Cell-based therapies are attractive for treating various degenerative disorders and cancer but delivering functional cells to the region of interest in vivo remains difficult. The problem is exacerbated in dense biological matrices such as solid tissues because these environments impose significant steric hindrances for cell movement. Here, we show that neural stem cells transfected with zinc-doped ferrite magnetic nanoparticles (ZnMNPs) can be pulled by an external magnet to migrate to the desired location in the brain. These magnetically labeled cells (Mag-Cells) can migrate because ZnMNPs generate sufficiently strong mechanical forces to overcome steric hindrances in the brain tissues. Once at the site of lesion, Mag-Cells show enhanced neuronal differentiation and greater secretion of neurotrophic factors than unlabeled control stem cells. Our study shows that ZnMNPs activate zinc-mediated Wnt signaling to facilitate neuronal differentiation. When implemented in a rodent brain stroke model, Mag-Cells led to significant recovery of locomotor performance in the impaired limbs of the animals. Our findings provide a simple magnetic method for controlling migration of stem cells with high therapeutic functions, offering a valuable tool for other cell-based therapies.
Bibliographical noteFunding Information:
This work was supported by grants from National Research Foundation (NRF; 2013M3A9B4076545 to K.I.P.), Korea Healthcare Technology R&D Project, Ministry for Health & Welfare Affairs (HI14C1564 and HI16C1089 to K.I.P., HI08C2149 to J.C.), and Institute for Basic Science (IBS-R026-D1 to J.C.). The authors thank Dr. Minsuk Kwak for helpful comments and discussions.
All Science Journal Classification (ASJC) codes
- Materials Science(all)
- Condensed Matter Physics
- Mechanical Engineering