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1.
Stem Cells Dev ; 18(2): 321-9, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18435573

RESUMEN

Intravenous delivery of mesenchymal stem cells (MSCs) preserves myocardial function after infarction. This dose-escalating study was performed to examine pathologic remodeling and scar formation in a pig model of permanent coronary occlusion without restoration of reperfusion. MSCs labeled with fluorescent dye 48 h or saline (negative control, n = 8) were given intravenously 48 h post proximal left anterior descending artery occlusion. Animals received either autologous or allogeneic MSCs in doses from 1 x 10(3) up to 1 x 10(6) per kg bodyweight from an unrelated donor pig. Infarct size and myocardial function were assessed after 1 month. Morphologic analysis revealed that labeled autologous MSCs migrated in the peri-infarct region resulting in smaller infarct size (19 +/- 7% vs. 32 +/- 7%, p < 0.008) and higher fractional area shortening (33 +/- 7% vs. 21 +/- 3%, p < 0.001). Similarly, allogeneic MSCs had dose-dependent beneficial effects on cardiac function, statistically significant at 1 x 10(5) and 1 x 10(6) cells per kg bodyweight. Autologous as well as allogeneic MSCs specifically "home" to the heart after systemic delivery, leading to limited myocardial infarct size and improved functional outcome, even without coronary reperfusion. Therefore, intravenously administration of MSCs is an attractive minimal-invasive approach for cardiac tissue repair.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Infarto del Miocardio/patología , Miocardio/patología , Animales , Peso Corporal , Circulación Coronaria , Oclusión Coronaria/diagnóstico por imagen , Fluorescencia , Pruebas de Función Cardíaca , Hemodinámica , Inyecciones Intravenosas , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Tamaño de los Órganos , Perfusión , Porcinos , Ultrasonografía , Aumento de Peso
2.
Scand Cardiovasc J ; 43(1): 39-45, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18609048

RESUMEN

OBJECTIVES: Intravenous delivery of mesenchymal stem cells (MSCs) is an attractive approach for regeneration of infarcted myocardium. However, its efficacy is not well-defined in large animals. METHODS: Pigs (n =8) received intravenously autologous, allogeneic porcine or human MSCs (1 x 10(6) per kg bodyweight) labeled with fluorescent dye 48 hours post proximal LAD occlusion. Infarct size, histology and myocardial function were assessed 4 weeks later. RESULTS: Labeled MSCs migrated in the peri-infarct region resulting in improved myocardial function. Infarct size was larger in the control group (32+/-7%) compared to autologous (19+/-7%, p =0.008), allogeneic (24+/-4%, p =0.01) and human MSCs (26+/-5%, p =0.03). Fractional area shortening significantly increased after 4 weeks in pigs receiving autologous MSCs (34+/-7%, p =0.001), allogeneic MSCs (28+/-2%, p =0.004) and human MSCs (24+/-5%, p =0.027), but was lower in the control group (23+/-3%, n.s.). However, substantial callus formation and a non-malignant cardiac "tumor" containing mesenchymal tissue was observed in one animal treated with human MSCs. CONCLUSIONS: Intravenously administered MSCs prevent pathologic remodeling and scar formation but bare potential risks from inflammatory-related products.


Asunto(s)
Neoplasias Cardíacas/etiología , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Infarto del Miocardio/cirugía , Miocardio/patología , Regeneración , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Neoplasias Cardíacas/patología , Humanos , Contracción Miocárdica , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Porcinos , Factores de Tiempo , Trasplante Autólogo , Trasplante Homólogo
3.
J Am Soc Echocardiogr ; 20(5): 512-20, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17484992

RESUMEN

OBJECTIVES: Intravenous delivery of mesenchymal stem cell (MSC) is a noninvasive approach for myocardial tissue repair. We aimed to test this strategy in a pig model of myocardial infarction and to examine the usefulness of new echocardiographic applications to monitor cardioprotective effects of stem cell therapy. METHODS: Pigs (n = 8) received autologous or allogeneic MSCs (1 x 10(6)/kg body weight) labeled with fluorescent dye 48 hours after proximal left anterior descending coronary artery occlusion. Infarct size, myocardial function, and perfusion (A x beta) were assessed by myocardial contrast echocardiography and standard histologic methods after 1 month. RESULTS: Morphologic analysis revealed that labeled MSCs migrated in the peri-infarct region resulting in smaller infarct size by myocardial contrast echocardiography (control vs autologous and allogeneic MSC: 38 +/- 10% vs 25 +/- 5% and 28 +/- 6%, P < .01), higher fractional area shortening (23 +/- 3% vs 34.0 +/- 7% and 28 +/- 2%, P < .01), higher cardiac synchrony (167 +/- 36 vs 68 +/- 17 and 85 +/- 26 milliseconds, P < .003), and improved microvascular flow A x beta in the ischemic border zone (0.18 +/- 0.2 vs 0.56 +/- 0.3 and 0.49 +/- 0.2, P < .03). CONCLUSIONS: Systemic delivery of autologous and allogeneic MSCs preserves myocardial viability even in large animals and is, therefore, an attractive approach for tissue repair. Myocardial contrast echocardiography is useful to evaluate microvascular perfusion, which was enhanced by MSCs.


Asunto(s)
Circulación Coronaria/fisiología , Ecocardiografía/métodos , Trasplante de Células Madre Mesenquimatosas/métodos , Contracción Miocárdica/fisiología , Infarto del Miocardio , Animales , Medios de Contraste/administración & dosificación , Modelos Animales de Enfermedad , Estudios de Seguimiento , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Inyecciones Intravenosas , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/cirugía , Porcinos , Resultado del Tratamiento
4.
Stem Cells Dev ; 16(1): 31-7, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17348804

RESUMEN

Systemic delivery of bone marrow-derived mesenchymal stem cells (MSCs) is a noninvasive approach for myocardial repair. We aimed to test this strategy in a pig model of myocardial infarction. Pigs (n = 8) received autologous MSCs (1 x 10(6)/kg body weight) labeled with fluorescent dye 48 h post proximal left anterior descending artery (LAD) occlusion. Hemodyamics, infarct size, and myocardial function were assessed at baseline and after 1 month. Morphologic analysis revealed that labeled MSCs migrated in the peri-infarct region, resulting in smaller infarct size (32 +/- 7 vs. 19 +/- 7%, p = 0.01), higher fractional area shortening (23 +/- 3 vs. 34.0 +/- 7%, p = 0.001), lower left ventricular end diastolic pressure (18.7 +/- 5 vs. 10.2 +/- 4 mmHg, p = 0.02) and higher +dp/dt (4,570 +/- 540 vs. 6,742 +/- 700 mmHg/s, p = 0.03) during inotropic stimulation. Systemic intravenous delivery of MSCs to pigs limits myocardial infarct size and is an attractive approach for tissue repair.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Función Ventricular Izquierda , Animales , Modelos Animales de Enfermedad , Corazón/fisiología , Trasplante de Células Madre Mesenquimatosas/métodos , Infarto del Miocardio/fisiopatología , Miocardio/patología , Porcinos , Trasplante Autólogo
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