title: Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model.
abstract: The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [(18)F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [(18)F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33-35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC-associated [(18)F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [(18)F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.
authors.affiliation: The Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, United States of America.
authors.forename: Emerson C
authors.initials: EC
authors.lastname: Perin
authors.forename: Mei
authors.initials: M
authors.lastname: Tian
authors.forename: Frank C
authors.initials: FC
authors.lastname: Marini
authors.forename: Guilherme V
authors.initials: GV
authors.lastname: Silva
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Fred
authors.initials: F
authors.lastname: Baimbridge
authors.forename: Xin
authors.initials: X
authors.lastname: Quan
authors.forename: Marlos R
authors.initials: MR
authors.lastname: Fernandes
authors.forename: Amir
authors.initials: A
authors.lastname: Gahremanpour
authors.forename: Daniel
authors.initials: D
authors.lastname: Young
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Paolillo
authors.forename: Uday
authors.initials: U
authors.lastname: Mukhopadhyay
authors.forename: Agatha T
authors.initials: AT
authors.lastname: Borne
authors.forename: Rajesh
authors.initials: R
authors.lastname: Uthamanthil
authors.forename: David
authors.initials: D
authors.lastname: Brammer
authors.forename: James
authors.initials: J
authors.lastname: Jackson
authors.forename: William K
authors.initials: WK
authors.lastname: Decker
authors.forename: Amer M
authors.initials: AM
authors.lastname: Najjar
authors.forename: Michael W
authors.initials: MW
authors.lastname: Thomas
authors.forename: Andrei
authors.initials: A
authors.lastname: Volgin
authors.forename: Brian
authors.initials: B
authors.lastname: Rabinovich
authors.forename: Suren
authors.initials: S
authors.lastname: Soghomonyan
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Rios
authors.forename: David
authors.initials: D
authors.lastname: Steiner
authors.forename: Simon
authors.initials: S
authors.lastname: Robinson
authors.forename: Osama
authors.initials: O
authors.lastname: Mawlawi
authors.forename: Tinsu
authors.initials: T
authors.lastname: Pan
authors.forename: Jason
authors.initials: J
authors.lastname: Stafford
authors.forename: Vikas
authors.initials: V
authors.lastname: Kundra
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Mian M
authors.initials: MM
authors.lastname: Alauddin
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shpall
authors.forename: Juri G
authors.initials: JG
authors.lastname: Gelovani
mesh_terms: D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives; D002454:Cell Differentiation; D002460:Cell Line; D002469:Cell Separation; D002470:Cell Survival; D004195:Disease Models, Animal; D004452:Echocardiography; D042783:Endothelial Cells / Q000000981:diagnostic imaging / Q000473:pathology; D005240:Feasibility Studies; D017930:Genes, Reporter / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000201:enzymology; D008198:Lymph Nodes / Q000473:pathology; D042601:Lymphatic Vessels / Q000473:pathology; D008220:Lymphography; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000000981:diagnostic imaging / Q000378:metabolism; D051379:Mice; D009203:Myocardial Infarction / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D013552:Swine; D013937:Thymidine Kinase / Q000235:genetics; D013997:Time Factors; D014057:Tomography, X-Ray Computed
chemical_list: C508411:2'-fluoro-2'-deoxy-5-fluoroethyl-1-beta-D-arabinofuranosyl uracil; D001086:Arabinofuranosyluracil; D013937:Thymidine Kinase