title: Non-invasive monitoring of transplanted endothelial progenitor cells in diabetic ischemic stroke models.
abstract: Endogenous endothelial progenitor cells (EPCs) are functionally impaired in hyperglycemia through the p38 MAPK signaling pathway. However, the number and function of transplanted exogenous EPCs in diabetic animals remains unclear. The objectives of this study were to establish a non-invasive imaging strategy to monitor the homing of transplanted EPCs in diabetic stroke mice and to assess the effect of RWJ 67657, an inhibitor of p38 MAPK, on the homing ability of exogenous EPCs. Bone marrow-derived EPCs were labeled in vitro with a multi-functional nanoprobe modified with paramagnetic chelators and fluorophores before being infused into stroke mice. The signal of the nanoprobe reached its peak on day 5 in both magnetic resonance imaging and near-infrared fluorescence imaging after EPC transplantation in wild-type stroke models. The signal enhancement of diabetic stroke models was significantly lower than that of wild-type controls. However, the signal intensity of diabetic stroke models significantly increased after oral administration of RWJ 67657, indicating that more transplanted EPCs migrated to the ischemic brain. Furthermore, the increased exogenous EPCs induced remarkably greater angiogenesis after stroke. These results suggest that this dual-modal imaging strategy is feasible for non-invasively monitoring transplanted cells in vivo.
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Bai
authors.affiliation: Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Lishan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Xin-Gui
authors.initials: XG
authors.lastname: Peng
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Yuan-Cheng
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Di
authors.initials: D
authors.lastname: Chang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China. Electronic address: jsh0836@hotmail.com.
authors.forename: Shenghong
authors.initials: S
authors.lastname: Ju
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000628:therapy*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000628:therapy*; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D007093:Imidazoles / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D013194:Staining and Labeling; D020521:Stroke / Q000150:complications / Q000628:therapy*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D007093:Imidazoles; D011725:Pyridines; C400277:RWJ 67657; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Angiogenesis; Diabetes mellitus; Endothelial progenitor cells; Ischemic stroke; Nanoprobe; p38 MAPK