Stem Cells for Myocardial Regeneration

Penn, Marc S.; Dong, Feng; Klein, Shannon G.; Mayorga, Maritza E.

doi:10.1038/clpt.2011.196

Cited by 24 publications

(23 citation statements)

References 10 publications

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“…4,19,32,33 As shown here, through careful delineation of relevant molecular mechanisms we can define key molecular targets for which gene transfer can be utilized to induce endogenous repair systems, define parameters that optimize clinical trial design and develop therapeutics that will be potentially less complicated to implement, safer for the patients and less costly to the system. 34 CONFLICT OF INTEREST Drs Aras, Miller and Pastore are employees of Juventas Therapeutics as such receive salary and stock options from the companies. Dr Penn is named as an inventor on patent applications filed for the use of SDF-1 for the treatment of ischemic tissue injury.…”

Section: Discussionmentioning

confidence: 99%

SDF-1 in myocardial repair

et al. 2012

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Stem cell therapy for the prevention and treatment of cardiac dysfunction holds significant promise for patients with ischemic heart disease. Excitingly early clinical studies have demonstrated safety and some clinical feasibility, while at the same time studies in the laboratory have investigated mechanisms of action and strategies to optimize the effects of regenerative cardiac therapies. One of the key pathways that has been demonstrated critical in stem cell-based cardiac repair is (stromal cell-derived factor-1) SDF-1:CXCR4. SDF-1:CXCR4 has been shown to affect stem cell homing, cardiac myocyte survival and ventricular remodeling in animal studies of acute myocardial infarction and chronic heart failure. Recently released clinical data suggest that SDF-1 alone is sufficient to induce cardiac repair. Most importantly, studies like those on the SDF-1:CXCR4 axis have suggested mechanisms critical for cardiac regenerative therapies that if clinical investigators continue to ignore will result in poorly designed studies that will continue to yield negative results. Gene Therapy (2012) 19, 583-587; doi:10.1038/gt.2012.32Keywords: acute myocordial infarction; regenerative medicine; stem cells; chemokines INTRODUCTIONOver a decade ago we hypothesized that stem cell-based repair of ischemic tissue is a natural response to tissue injury but that it is clinically inefficient because of the short-lived nature of the molecular signals regulating the process, not a lack of stem cells. At that time it was of great interest to us that stem cells in the blood stream homed to the myocardium in animal models of acute myocardial infarction (AMI), but not in models of chronic ischemic cardiomyopathy. These observations led us to investigate potential regulators of stem cell homing. We eventually identified stromal cell-derived factor-1 (SDF-1, aka CXCL12) as the key regulator of stem cell migration to sites of tissue injury. 1 More recently studies have extended the relevance of the SDF-1:CXCR4 axis by demonstrating its critical importance in cardiogenic specification during development. 2 As that initial observation we have demonstrated that transient engineered-cell-based 3 or plasmid-based 4 overexpression of SDF-1 in ischemic cardiomyopathy improved cardiac function. Furthermore, we have demonstrated that delivery of mesenchymal stem cells engineered to overexpress SDF-1 at the time of AMI leads to improvement in cardiac function. 5 Research by our laboratory and others have demonstrated that mechanism of action of SDF-1 overexpression in AMI and chronic heart failure (CHF) are clearly multifactorial including both systemic and direct trophic effects. [4][5][6] The initiation of endogenous stem cell-based repair appears blunted because of the natural short-term expression of SDF-1 at the time of AMI. 1 Furthermore, there appears to be commonalities associated with the mechanisms of action of SDF-1 in AMI and CHF as well as some distinct differences. We were the first to show that SDF-1 leads to the recruitment of cardiac st...

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Section: Discussionmentioning

confidence: 99%

SDF-1 in myocardial repair

et al. 2012

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“…16,32 Improvements are mostly attributed to the effects of paracrine factors released from cells. 26,36,37 Promptly after transplantation into injured myocardium, stem cells express a variety of paracrine secretions, including cytokines, chemokines, and growth factors. 7 These appear to contribute to cardiac repair; 36 possibly through neo-vascularization, angiogenesis, 36 less inflammation, 32,36 smaller infarct size, 32,36,38 and decreased fibrosis.…”

Section: Mechanismsmentioning

confidence: 99%

“…33,[40][41][42] SDF-1 regulates cell trafficking, 39 increases angiogenesis and cell survival, 40 and improves ventricular function. 41 SDF-1 is not naturally released in chronic ischemic myopthy, 33,37 although homing can be established if paracrine factors are released at a time remote from AMI. 33 SDF-1 is expressed immediately post-AMI and declines after 4-7 days; a time when cells are considered most responsive to SDF-1.…”

Section: Mechanismsmentioning

confidence: 99%

Stem Cell Therapy for Heart Disease

2013

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Coronary artery disease is the leading cause of death in Americans. After myocardial infarction, significant ventricular damage persists despite timely reperfusion and pharmacological management. Treatment is limited, as current modalities do not cure this damage. In the past decade, stem cell therapy has emerged as a promising therapeutic solution to restore myocardial function. Clinical trials have demonstrated safety and beneficial effects in patients suffering from acute myocardial infarction, heart failure, and dilated cardiomyopathy. These benefits include improved ventricular function, increased ejection fraction, and decreased infarct size. Mechanisms of therapy are still not clearly understood. However, it is believed that paracrine factors, including stromal cell-derived factor-1, contribute significantly to stem cell benefits. The purpose of this article is to provide medical professionals with an overview on stem cell therapy for the heart and to discuss potential future directions.

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“…En este sentido, para que los nuevos descubrimientos sean de beneficio para los pacientes y la población en riesgo de desarrollar enfermedades cardiovasculares, se requieren diferentes pasos integrados en una cadena de valor (14)(15)(16). Por ejemplo, se parte de las necesidades y de los vacíos de conocimiento para afrontar problemas y necesidades de salud global no resueltos, y se formulan y se desarrollan investigaciones iniciales; luego, el conocimiento científico inicial puede conducir al desarrollo y evaluación de potenciales aplicaciones, bienes y servicios en salud, seguidos por la validación y la prescripción de recomendaciones basadas en la "evidencia", para la práctica clínica y para la toma de decisiones en salud.…”

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“…Por ejemplo, intervenciones dirigidas hacia procesos moleculares y celulares específicos que subyacen a la biología y a la patogenia de las enfermedades cardiovasculares (14)(15)(16).…”

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Las enfermedades cardiovasculares: un problema de salud pública y un reto global

Gómez

2011

biomedica

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EditorialLas enfermedades cardiovasculares: un problema de salud pública y un reto global Las enfermedades cardiovasculares son responsables de la mayor parte de las muertes en el mundo. De acuerdo con el Informe del Estado Global en Salud de la Organización Mundial de la Salud (OMS), publicado en abril de 2011 (1), las enfermedades crónicas no transmisibles fueron la causa de, aproximadamente, el 63 % (36 millones) del total (57 millones) de muertes ocurridas en el mundo en el año 2008. De las cuatro principales enfermedades crónicas no transmisibles -las enfermedades cardiovasculares, el cáncer, la diabetes y las enfermedades respiratorias crónicas-las cardiovasculares fueron las causantes del 29,82 % (17 millones) de las muertes (1).La OMS estimó la mortalidad y la prevalencia de enfermedades crónicas en cada estado miembro. Resulta alarmante que, en todos los continentes, con la excepción de África, las muertes por enfermedades no transmisibles superan las de las enfermedades transmisibles, maternas y perinatales, nutricionales y causas combinadas (1,2).En los países desarrollados, por ejemplo, los Estados Unidos, más de 2.200 personas mueren de enfermedades cardiovasculares cada año y éstas son la causa de una de cada 2,9 muertes; además, en promedio, cada día muere una persona cada 39 segundos en este país (1-4). En los países europeos se observa una tendencia similar a la de los norteamericanos. Para los hombres europeos, por ejemplo, las muertes por las enfermedades crónicas no transmisibles son 13 veces más altas que otras causas combinadas, y para los hombres en la región occidental del Pacífico, son ocho veces mayor (1-3).La muerte por enfermedades infecciosas ha disminuido en la mayoría de los países en las últimas décadas. A medida que los países más pobres mejoren sus condiciones de vida, es probable que sus sistemas de salud mejoren y que se reduzcan los niveles de enfermedades infecciosas y parasitarias. A pesar de la prevalencia de las enfermedades transmisibles (como el VIH/sida, la malaria y la tuberculosis), las enfermedades cardiovasculares siguen en aumento en el número de muertes y cobran más "años de vida perdidos" en los países en desarrollo, porque afectan no sólo a personas mayores, sino también a personas jóvenes (4,5).

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Stem Cells for Myocardial Regeneration

Cited by 24 publications

References 10 publications

SDF-1 in myocardial repair

SDF-1 in myocardial repair

Stem Cell Therapy for Heart Disease

Las enfermedades cardiovasculares: un problema de salud pública y un reto global

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