title: Magnetic resonance imaging of bone marrow cell-mediated interleukin-10 gene therapy of atherosclerosis.
abstract: BACKGROUND
  A characteristic feature of atherosclerosis is its diffuse involvement of arteries across the entire human body. Bone marrow cells (BMC) can be simultaneously transferred with therapeutic genes and magnetic resonance (MR) contrast agents prior to their transplantation. Via systemic transplantation, these dual-transferred BMCs can circulate through the entire body and thus function as vehicles to carry genes/contrast agents to multiple atherosclerosis. This study was to evaluate the feasibility of using in vivo MR imaging (MRI) to monitor BMC-mediated interleukin-10 (IL-10) gene therapy of atherosclerosis.
  
  
  METHODS
  For in vitro confirmation, donor mouse BMCs were transduced by IL-10/lentivirus, and then labeled with a T2-MR contrast agent (Feridex). For in vivo validation, atherosclerotic apoE(-/-) mice were intravenously transplanted with IL-10/Feridex-BMCs (Group I, n = 5) and Feridex-BMCs (Group II, n = 5), compared to controls without BMC transplantation (Group III, n = 5). The cell migration to aortic atherosclerotic lesions was monitored in vivo using 3.0T MRI with subsequent histology correlation. To evaluate the therapeutic effect of BMC-mediated IL-10 gene therapy, we statistically compared the normalized wall indexes (NWI) of ascending aortas amongst different mouse groups with various treatments.
  
  
  RESULTS
  Of in vitro experiments, simultaneous IL-10 transduction and Feridex labeling of BMCs were successfully achieved, with high cell viability and cell labeling efficiency, as well as IL-10 expression efficiency (≥90%). Of in vivo experiments, MRI of animal groups I and II showed signal voids within the aortic walls due to Feridex-created artifacts from the migrated BMCs in the atherosclerotic plaques, which were confirmed by histology. Histological quantification showed that the mean NWI of group I was significantly lower than those of group II and group III (P<0.05).
  
  
  CONCLUSIONS
  This study has confirmed the possibility of using MRI to track, in vivo, IL-10/Feridex-BMCs recruited to atherosclerotic lesions, where IL-10 genes function to prevent the progression of atherosclerosis.
authors.affiliation: Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Sun
authors.forename: Xubin
authors.initials: X
authors.lastname: Li
authors.forename: Hongqing
authors.initials: H
authors.lastname: Feng
authors.forename: Huidong
authors.initials: H
authors.lastname: Gu
authors.forename: Tiffany
authors.initials: T
authors.lastname: Blair
authors.forename: Jiakai
authors.initials: J
authors.lastname: Li
authors.forename: Stephanie
authors.initials: S
authors.lastname: Soriano
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Meng
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Feng
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000473:pathology* / Q000628:therapy*; D001854:Bone Marrow Cells / Q000378:metabolism*; D002478:Cells, Cultured; D015316:Genetic Therapy / Q000379:methods*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D016753:Interleukin-10