Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging

Journal of Nanobiotechnology

Research

David C Spray¹  Linda A Jelicks²  Emerson L Gasparetto³  Juliana A Passipieri⁴  Rosalia Mendez-Otero⁴  Ana Luiza M Torres⁴  Henrique MP Nunes⁴  Antonio C Campos de Carvalho⁵ 

[1] Dept. of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA;Dept. of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA;Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Dept. of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA;

关键词: Protamine;    Prussian Blue;    Chondrogenic Differentiation;    Magnetic Resonance Imaging Contrast Agent;    Superparamagnetic Iron Oxide Nanoparticles;   

DOI  :  10.1186/1477-3155-9-4

 received in 2010-10-11, accepted in 2011-02-09,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundStem cell therapy has emerged as a promising addition to traditional treatments for a number of diseases. However, harnessing the therapeutic potential of stem cells requires an understanding of their fate in vivo. Non-invasive cell tracking can provide knowledge about mechanisms responsible for functional improvement of host tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label and visualize various cell types with magnetic resonance imaging (MRI). In this study we performed experiments designed to investigate the biological properties, including proliferation, viability and differentiation capacity of mesenchymal cells (MSCs) labeled with clinically approved SPIONs.ResultsRat and mouse MSCs were isolated, cultured, and incubated with dextran-covered SPIONs (ferumoxide) alone or with poly-L-lysine (PLL) or protamine chlorhydrate for 4 or 24 hrs. Labeling efficiency was evaluated by dextran immunocytochemistry and MRI. Cell proliferation and viability were evaluated in vitro with Ki67 immunocytochemistry and live/dead assays. Ferumoxide-labeled MSCs could be induced to differentiate to adipocytes, osteocytes and chondrocytes. We analyzed ferumoxide retention in MSCs with or without mitomycin C pretreatment. Approximately 95% MSCs were labeled when incubated with ferumoxide for 4 or 24 hrs in the presence of PLL or protamine, whereas labeling of MSCs incubated with ferumoxide alone was poor. Proliferative capacity was maintained in MSCs incubated with ferumoxide and PLL for 4 hrs, however, after 24 hrs it was reduced. MSCs incubated with ferumoxide and protamine were efficiently visualized by MRI; they maintained proliferation and viability for up to 7 days and remained competent to differentiate. After 21 days MSCs pretreated with mitomycin C still showed a large number of ferumoxide-labeled cells.ConclusionsThe efficient and long lasting uptake and retention of SPIONs by MSCs using a protocol employing ferumoxide and protamine may be applicable to patients, since both ferumoxides and protamine are approved for human use.

【 授权许可】

CC BY   
© Jasmin et al; licensee BioMed Central Ltd. 2011