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Nano Lett. 2018 Feb 14;18(2):838-845. doi: 10.1021/acs.nanolett.7b04089. Epub 2018 Feb 2.

Design of Magnetically Labeled Cells (Mag-Cells) for in Vivo Control of Stem Cell Migration and Differentiation.

Yun S1, Shin TH2,3,4, Lee JH2,3,4, Cho MH2,3,4, Kim IS5, Kim JW2,3,4, Jung K5, Lee IS5, Cheon J2,3,4, Park KI1,5.

Author information

1
Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine , Seoul 03722, Korea.
2
Center for NanoMedicine, Institute for Basic Science (IBS) , Seoul 03722, Korea.
3
Yonsei-IBS Institute, Yonsei University , Seoul 03722, Korea.
4
Department of Chemistry, Yonsei University , Seoul 03722, Korea.
5
Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine , Seoul 03722, Korea.

Abstract

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.

KEYWORDS:

Magnetic nanoparticles; cell therapy; magnetic targeting; stem cell delivery; stem cell differentiation

PMID:
29393650
DOI:
10.1021/acs.nanolett.7b04089
[Indexed for MEDLINE]

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