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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.

SUBMITTER: Perin EC

PROVIDER: S-EPMC3164664 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model.

Perin Emerson C EC Tian Mei M Marini Frank C FC Silva Guilherme V GV Zheng Yi Y Baimbridge Fred F Quan Xin X Fernandes Marlos R MR Gahremanpour Amir A Young Daniel D Paolillo Vincenzo V Mukhopadhyay Uday U Borne Agatha T AT Uthamanthil Rajesh R Brammer David D Jackson James J Decker William K WK Najjar Amer M AM Thomas Michael W MW Volgin Andrei A Rabinovich Brian B Soghomonyan Suren S Jeong Hwan-Jeong HJ Rios Jesse M JM Steiner David D Robinson Simon S Mawlawi Osama O Pan Tinsu T Stafford Jason J Kundra Vikas V Li Chun C Alauddin Mian M MM Willerson James T JT Shpall Elizabeth E Gelovani Juri G JG

PloS one 20110901 9

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 i ...[more]

PMID: 21912635

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Project description:ObjectivesThis study sought to determine the association of chronic stress with long-term adverse outcomes after acute myocardial infarction (AMI).BackgroundChronic stress has been shown to be associated with the development of cardiovascular disease and, in the case of particular types of stress such as job and marital strain, with recurrent adverse events after AMI. Little is known, however, about the association of chronic stress with mortality and adverse health status outcomes in a general AMI population.MethodsIn a cohort of 4,204 AMI patients from 24 U.S. hospitals completing the Perceived Stress Scale-4 (sum scores ranging from 0 to 16) during hospitalization, moderate/high stress over the previous month was defined as scores in the top 2 quintiles (scores of 6 to 16). Detailed data on sociodemographics, psychosocial status, and clinical characteristics were collected at baseline. Outcomes included patients' 1-year health status, assessed with the Seattle Angina Questionnaire, Short Form-12, and EuroQol Visual Analog Scale, and 2-year mortality.ResultsAMI patients with moderate/high stress had increased 2-year mortality compared with those having low levels of stress (12.9% vs. 8.6%; p < 0.001). This association persisted after adjusting for sociodemographics, clinical factors (including depressive symptoms), revascularization status, and GRACE (Global Registry of Acute Coronary Events) discharge risk scores (hazard ratio: 1.42: 95% confidence interval: 1.15 to 1.76). Furthermore, moderate/high stress was independently associated with poor 1-year health status, including a greater likelihood of angina, worse disease-specific and generic health status, and worse perceived health (p < 0.01 for all).ConclusionsModerate/high perceived stress at the time of an AMI is associated with adverse long-term outcomes, even after adjustment for important confounding factors. Future studies need to examine whether stress mediates observed racial and socioeconomic disparities and whether novel interventions targeting chronic stress and coping skills can improve post-AMI outcomes.

Dataset Information

Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model.

Publications

Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model.

Similar Datasets

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