Magnetic Targeting of Human Mesenchymal Stem Cells with Internalized Superparamagnetic Iron Oxide Nanoparticles

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 9; no. 23; pp. 4017 - 4026
• Main Authors: Landázuri, Natalia, Tong, Sheng, Suo, Jin, Joseph, Giji, Weiss, Daiana, Sutcliffe, Diane J., Giddens, Don P., Bao, Gang, Taylor, W. Robert
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 09-12-2013; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Bone marrow; cells; Ferric Compounds - chemistry; Human; Humans; Iron oxides; Magnetic fields; magnetic materials; Magnetite Nanoparticles - adverse effects; Magnetite Nanoparticles - chemistry; Mathematical models; Medical research; Mesenchymal Stromal Cells - cytology; modeling; Nanoparticles; Nanoparticles - adverse effects; Nanoparticles - chemistry; Nanotechnology; Polyethylenes; regenerative medicine; Stem cells; Therapy; cells; modeling; nanoparticles; regenerative medicine; magnetic materials
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201300570

Cell therapies offer exciting new opportunities for effectively treating many human diseases. However, delivery of therapeutic cells by intravenous injection, while convenient, relies on the relatively inefficient process of homing of cells to sites of injury. To address this limitation, a novel strategy has been developed to load cells with superparamagnetic iron oxide nanoparticles (SPIOs), and to attract them to specific sites within the body by applying an external magnetic field. The feasibility of this approach is demonstrated using human mesenchymal stem cells (hMSCs), which may have a significant potential for regenerative cell therapies due to their ease of isolation from autologous tissues, and their ability to differentiate into various lineages and modulate their paracrine activity in response to the microenvironment. The efficient loading of hMSCs with polyethylene glycol‐coated SPIOs is achieved, and it is found that SPIOs are localized primarily in secondary lysosomes of hMSCs and are not toxic to the cells. Further, the key stem cell characteristics, including the immunophenotype of hMSCs and their ability to differentiate, are not altered by SPIO loading. Through both experimentation and mathematical modeling, it is shown that, under applied magnetic field gradients, SPIO‐containing cells can be localized both in vitro and in vivo. The results suggest that, by loading SPIOs into hMSCs and applying appropriate magnetic field gradients, it is possible to target hMSCs to particular vascular networks.
Stem cells with internalized magnetic nanoparticles can be noninvasively targeted using an external magnetic field gradient. The effective delivery of polyethylene glycol‐coated superparamagnetic iron oxide nanoparticles into human mesenchymal stem cells with magnetic force is demonstrated.