Por favor, use este identificador para citar o enlazar este ítem: http://hdl.handle.net/10637/14852

Intravenously delivered mesenchymal stem cells: systemic anti-inflammatory effects improve left ventricular dysfunction in acute myocardial infarction and ischemic cardiomyopathy


Ver/Abrir:
 Intravenously_Luger_CR_2017.pdf
  Acceso restringido
6,17 MB
Adobe PDF
 Request a copy
Ver/Abrir:
 Intravenously_Luger_CR_2017.JPG
155,78 kB
JPEG
Título : Intravenously delivered mesenchymal stem cells: systemic anti-inflammatory effects improve left ventricular dysfunction in acute myocardial infarction and ischemic cardiomyopathy
Autor : Luger, Dror
Lipinski, Michael J.
Westman, Peter C.
Glover, David K.
Dimastromatteo, Julien
Frías Martínez, Juan Carlos
Albelda, M. Teresa
Sikora, Sergey
Kharazi, Alex
Vertelov, Grigory
Waksman, Ron
Epstein, Stephen E.
Materias: CélulaCellsEnfermedad cardiovascularCardiovascular diseases
Editorial : American Heart Association
Citación : Luger, D., Lipinski, M.J., Westman, P.C., Glover, D.K., Dimastromatteo, J., Frias, J.C., Albelda, M.T., Sikora, S., Kharazi, A., Vertelov, G., Waksman, R., & Epstein, S.E. (2017). Intravenously delivered mesenchymal stem cells: systemic anti-inflammatory effects improve left ventricular dysfunction in acute myocardial infarction and ischemic cardiomyopathy. Circulation Research, vol. 120, i. 10 (17 may.), pp. 1598–1613. DOI: https://doi.org/10.1161/CIRCRESAHA.117.310599
Resumen : Rationale:Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm. Objective:To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post–acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities. Methods and Results:Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O2, were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×106) were injected 24 hours post–myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×106 MSCs or saline intravenously 24 hours post–myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre–acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post–myocardial infarction were randomized to tail-vein injection of 2×106 MSCs, with injection repeated at week 3 (n=16) versus PBS control (n=16). MSCs significantly increased LV ejection fraction and decreased LV end-systolic volume. Conclusions:Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities.
Descripción : Este recurso no está disponible en acceso abierto por política de la editorial.
URI : http://hdl.handle.net/10637/14852
ISSN : 0009-7330
Fecha de publicación : 12-may-2017
Centro : Universidad Cardenal Herrera-CEU
Aparece en las colecciones: Dpto. Ciencias Biomédicas





Los ítems de DSpace están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.