title: MRI of iron oxide nanoparticle-labeled ADSCs in a model of hindlimb ischemia.
abstract: Adipose-derived stem cells (ADSCs) exhibit tremendous potential for repair of ischemic diseases. However, studies on the fate, migration, differentiation, and body distribution of the labeled ADSCs are rarely reported. In this study, magnetic iron oxide nanoparticles were designed, synthesized, and coated with meso-2,3-dimercaptosuccinic acid (DMSA) to produce DMSA nanoparticles (DMSA-NPs). The properties, size distribution, and characterization of DMSA-NPs were evaluated. Green fluorescent protein expressing ADSCs (GFP-ADSCs) were obtained and labeled with DMSA-NPs. The viability, cytotoxicity and multi-differentiation capacity of labeled GFP-ADSCs were evaluated in vitro. Labeled and non-labeled GFP-ADSCs were injected into a mouse model of hindlimb ischemia, and 3T magnetic resonance imaging (MRI) was acquired. The synthesized DMSA-NPs efficiently labeled the GFP-ADSCs in vitro and in vivo without affecting cell viability, proliferation, cell cycle, and multi-differentiation capacity. The MRI showed hypointense spots in the labeled GFP-ADSCs that lasted up to 8 weeks. Prussian blue staining and immunofluorescence assay at 4 and 8 weeks indicated that the labeled GFP-ADSCs were in and around the ischemic sites and some differentiated into capillaries. This observation is identical to that seen for transplants of unlabeled cells. Labeled cells were also identified mainly in the liver and spleen, with significantly smaller amounts in the lungs, intestines, heart, and kidney. Developed DMSA-NPs were shown to exhibit a considerable potential for use as nanoprobes for MRI of stem cells, which will enhance our understanding of cell-based therapeutic strategies for ischemic diseases.
authors.affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai 200011, PR China.
authors.forename: Jinbao
authors.initials: J
authors.lastname: Qin
authors.forename: Kangan
authors.initials: K
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Peng
authors.forename: Xiangxiang
authors.initials: X
authors.lastname: Li
authors.forename: Jiaying
authors.initials: J
authors.lastname: Lin
authors.forename: Kaichuang
authors.initials: K
authors.lastname: Ye
authors.forename: Xinrui
authors.initials: X
authors.lastname: Yang
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Xie
authors.forename: Zunli
authors.initials: Z
authors.lastname: Shen
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Jin
authors.forename: Mier
authors.initials: M
authors.lastname: Jiang
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhang
authors.forename: Xinwu
authors.initials: X
authors.lastname: Lu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005290:Ferric Compounds; D005295:Ferrocyanides; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology; D057446:Hydrodynamics; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000648:ultrastructure; D010316:Particle Size; D013194:Staining and Labeling; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004113:Succimer
chemical_list: D005290:Ferric Compounds; D005295:Ferrocyanides; D049452:Green Fluorescent Proteins; C000499:ferric oxide; D004113:Succimer; C000170:ferric ferrocyanide