Implante endoscópico de mioblastos autólogos en el tratamiento de la incontinencia urinaria de esfuerzo y evaluación de su eficacia en conejos sometidos a esfinterotomía / Endoscopic implantation of autologous myoblasts for stress urinary incontinence and evaluation of its efficacy in sphincterotomized rabbits

Introducción La incontinencia urinaria de esfuerzo (IUE) constituye uno de los problemas de salud con mayor impacto en la vida de las personas. El objetivo del presente trabajo fue desarrollar una terapia para IUE dentro de la ingeniería de tejidos mediante aislamiento y cultivo de mioblastos autólogos (MAC), su implante endoscópico y el estudio de su eficacia en un modelo de incontinencia por esfinterotomía desarrollado en conejos. Materiales y métodos Se utilizaron conejos Nueva Zelanda, machos, sanos. Los animales fueron primero sangrados para obtención del plasma pobre en plaquetas (PPP) y biopsiados para el aislamiento de mioblastos. Posesfinterotomía, fueron divididos en dos grupos: grupo tratado (representado por aquellos animales que recibieron MAC resuspendidos en PPP) y grupo control (representado por aquellos animales que recibieron solo PPP). Se utilizó el punto de presión de pérdida (LPP) para medir la continencia de ambos grupos en diferentes instancias. Los resultados se evaluaron con modelos de regresión lineal jerárquica. Se efectuaron también estudios histológicos sobre los esfínteres de los conejos una vez finalizado el seguimiento. Resultados No se observaron diferencias estadísticamente significativas entre los valores basales de LPP de cada grupo. Los valores posesfinterotomía de ambos grupos estuvieron por debajo del 50% del valor basal, condición necesaria para considerarlos sujetos incontinentes. Los valores posimplante del grupo tratado fueron superiores al 50% del valor basal, permitiendo suponer una recuperación de la continencia. Se observó una diferencia estadísticamente significativa en los valores de LPP entre los dos grupos de tratamiento (p=0,003). El estudio histológico en el grupo tratado reveló islas interconectadas formadas por fibras musculares, mientras que en el grupo control se observó tejido conectivo periférico a la luz de la uretra e infiltrado inflamatorio. Discusión y conclusiones ... (AU)

Introduction Stress urinary incontinence (SUI) is one of the health problems with more impact on patients’ lives. The aim of the present work was to develop a therapy for SUI using tissue engineering by isolation and culture of autologous myoblasts (CAM) followed by endoscopic implantation. We also evaluated the efficacy of this therapy in a rabbit model of incontinence after sphincterotomy. Materials and methods We used healthy male New Zealand rabbits. The animals were first bled to obtain platelet-poor plasma (PPP) and biopsied for myoblast isolation. Post-sphincterotomy, they were divided into two groups: the treatment group (including animals that received CAM resuspended in PPP) and the control group (including animals receiving only PPP). The leak-point pressure (LPP) was used to measure continence in both groups at different time points. The results were evaluated with hierarchical linear regression models. Histological evaluation of the rabbits’ sphincters was also performed at the end of follow-up. Results No statistically significant differences were observed between the baseline LPP values of each group. The post-sphincterotomy values of both groups were below 50% of the baseline value, which was a mandatory condition for incontinence. The post-implantation values of the treatment group were higher than 50% of the baseline value, which led us to assume continence recovery. A statistically significant difference was observed in the LPP values between the two treatment groups (p=0.003). Histological study revealed interconnected islands formed by muscle fibers in the treatment group, and connective tissue surrounding the urethral lumen and inflammatory infiltrate in the control group. Discussion and conclusions The implantation of CAM significantly improved LPP values in the treatment group, and the improvement remained throughout the evaluation period. ... (AU)

Endoscopic implantation of autologous myoblasts for stress urinary incontinence and evaluation of its efficacy in sphincterotomized rabbits.

INTRODUCTION: Stress urinary incontinence (SUI) is one of the health problems with more impact on patients' lives. The aim of the present work was to develop a therapy for SUI using tissue engineering by isolation and culture of autologous myoblasts (CAM) followed by endoscopic implantation. We also evaluated the efficacy of this therapy in a rabbit model of incontinence after sphincterotomy. MATERIALS AND METHODS: We used healthy male New Zealand rabbits. The animals were first bled to obtain platelet-poor plasma (PPP) and biopsied for myoblast isolation. Post-sphincterotomy, they were divided into two groups: the treatment group (including animals that received CAM resuspended in PPP) and the control group (including animals receiving only PPP). The leak-point pressure (LPP) was used to measure continence in both groups at different time points. The results were evaluated with hierarchical linear regression models. Histological evaluation of the rabbits' sphincters was also performed at the end of follow-up. RESULTS: No statistically significant differences were observed between the baseline LPP values of each group. The post-sphincterotomy values of both groups were below 50% of the baseline value, which was a mandatory condition for incontinence. The post-implantation values of the treatment group were higher than 50% of the baseline value, which led us to assume continence recovery. A statistically significant difference was observed in the LPP values between the two treatment groups (p=0.003). Histological study revealed interconnected islands formed by muscle fibers in the treatment group, and connective tissue surrounding the urethral lumen and inflammatory infiltrate in the control group. DISCUSSION AND CONCLUSIONS: The implantation of CAM significantly improved LPP values in the treatment group, and the improvement remained throughout the evaluation period. It may be associated with the consistency of the implant and its stability at the injection site. Longer follow-up studies and human clinical investigations are required to consider CAM implantation as an alternative treatment for stress urinary incontinence.

Myostatin coordinating the proliferation and differentiation of adipose and skeletal muscle cells and energy metabolism balance based on gene chip technology / A miostatina na coordenação da proliferação e diferenciação de células musculares adiposas e esqueléticas e no equilíbrio do metabolismo energético com base na tecnologia de chips genéticos / Msrn, basado en la tecnología de chips genéticos, coordina la fertilización y el metabolismo de las células musculares grasas y óseas

ABSTRACT Myoblasts fuse into multinucleated muscle fibers to form and promote the growth of skeletal muscle. In order to analyze the role of myostatin (MSTN) in body fat, skeletal muscle cell proliferation and differentiation and energy metabolism, this study will use the antisense RNA technology of gene chip technology to study it. The results showed that the MSTN gene regulated the growth and proliferation of myoblasts and affected the development of skeletal muscle by affecting the expression of Cdc42, bnip2, p38 and other genes; knockout or overexpression of the MSTN gene would lead to a trend of fat-related genes from fat synthesis to fat decomposition; after the MSTN gene was knocked down, the expression levels of cpti-b, PPARG and other genes in the cells were corresponding after MSTN overexpression, the relative expression of the PPARG gene decreased. It is suggested that the knockout or overexpression of MSTN may affect lipid accumulation, and cpti-b and PPARG may directly regulate lipid level. It is hoped that this experiment can provide a reference for the study of MSTN effect on fat deposition.

RESUMO Os mioblastos se fundem eM fibras musculares multinucleadas para formar e promover o crescimento do músculo esquelético. A fim de analisar o papel da miostatina (MSTN) na gordura corporal, proliferação de células musculares esqueléticas e diferenciação e metabolismo energético, este estudo utilizará a tecnologia anti-RNA de chips genéticos para estudá-la. Os resultados mostraram que o gene MSTN regulava o crescimento e a proliferação de mioblastos e afetava o desenvolvimento do músculo esquelético, afetando a expressão de Cdc42, bnip2, p38 e outros genes; a eliminação ou sobrexpressão do gene MSTN conduziria a uma tendência de os genes adiposos sintetizarem a gordura até sua decomposição; após a eliminação do gene MSTN, os níveis de expressão de cpti-b, PPARG e outros genes nas células mostraram-se correspondentes após a sobrexpressão do gene MSTN, e a expressão relativa do gene PPARG diminuiu. Sugere-se que a eliminação ou sobrexpressão da MSTN possa afetar a acumulação de lipídeos, e o cpti-b e o PPARG podem regular diretamente o nível lipídico. Espera-se que esta experiência possa fornecer uma referência para o estudo do efeito da MSTN sobre a deposição de gordura.

RESUMEN Los mioblastos se funden en fibras musculares multinucleadas para formar y promover el crecimiento del músculo esquelético. A fin de analizar el papel de la miostatina (MSTN) en la grasa corporal, proliferación de células musculares esqueléticas y diferenciación y metabolismo energético, este estudio utilizará la tecnología anti-RNA de chips genéticos para estudiarla. Los resultados mostraron que el gen MSTN regulaba el crecimiento y la proliferación de mioblastos y afectaba el desarrollo del músculo esquelético, afectando la expresión de Cdc42, bnip2, p38 y otros genes; la eliminación o sobreexpresión del gen MSTN conduciría a una tendencia de que los genes adiposos sinteticen la grasa hasta su descomposición; después de la eliminación del gen MSTN, los niveles de expresión de cpti-b, PPARG y otros genes en las células se mostraron correspondientes después de la sobreexpresión del gen MSTN, y la expresión relativa del gen PPARG disminuyó. Se sugiere que la eliminación o sobreexpresión de la MSTN pueda afectar la acumulación de lipídos, y el cpti-b y el PPARG pueden regular directamente el nivel lipídico. Se espera que esta experiencia pueda proveer una referencia para el estudio del efecto de la MSTN sobre el depósito de grasa.

Effects of nutritional status on mitochondrial Ca2+ handling / Efeitos do estado nutricional no manejo de Ca2+ mitocondrial

Mitochondria are central players in cell metabolism, responsible for the vast majority of ATP production in most cells. Although originally thought to be passive organelles focused only in keeping cellular ATP at adequate levels, complex interplay between mitochondrial function and cell signaling has been largely recognized over the last decades. Not surprisingly, given their role, changes in nutritional status promoted by chronic interventions like caloric restriction or short-term situations like fasting in animals or nutrient deprivation in cultured cells are one of the main factors that can activate those signaling mechanisms. One particular way in which this mitochondria-cell crosstalk can occur is through mitochondrial Ca2+ handling, a process in which Ca2+ signals generated by the cell are able to translate into elevations in mitochondrial matrix [Ca2+] due to the presence of the mitochondrial Ca2+ uniporter in the organelle. While the impact of mitochondrial Ca2+ handling on cellular function has been widely studied, the conditions which can modulate the process of mitochondrial Ca2+ handling itself are still not well characterized. In this work, we sought to test the effects of different interventions linked to nutritional status on mitochondrial Ca2+ handling. We found that caloric restriction, physiological fasting and modulations of mitochondrial dynamics resulted in modulation of mitochondrial Ca2+ handling through changes in their maximal Ca2+ retention capacity or Ca2+ uptake rates. These changes were, measured by following mitochondrial Ca2+ uptake using different strategies, employing the fluorescent Ca2+ probe Ca2+ Green 5N for experiments in isolated mitochondria and permeabilized cells and the cytosolic probe Fura2-AM in intact cells. Caloric restriction resulted in higher calcium uptake and retention in liver mitochondria, protecting against pathological conditions of Ca2+ overload during ischemia/reperfusion. On the other hand, overnight and short term fasting resulted in lower mitochondrial Ca2+ retention and oxidative phosphorylation capacity in the liver. Modulating mitochondrial morpholoy in C2C12 myoblasts showed that more fragmented mitochondria were less capable of taking up Ca2+, while more fusioned mitochondria showed the opposite phenotype. This modulation in Ca2+ handling through changes in mitochondrial morphology interfered with the process of Store-Operated Ca2+ entry in the cells, showing that these modulations can have impacts in physiological contexts as well. Overall, this work both establishes novel mechanisms of modulation of mitochondrial Ca2+ handling and demonstrates their relevance both in pathology and normal cellular physiology

Mitocôndrias possuem um papel central no metabolismo das células, sendo responsáveis pela maioria da produção de ATP na maioria dos tipos celulares. Embora originalmente se pensasse nas mitocôndrias como organelas estáticas, focadas somente em manter os níveis adequados de ATP na célula, a interação entre a função mitocondrial e a sinalização celular tem sido fortemente reconhecida nas ultimas décadas. Dado este papel, não é surpreendente que mudanças no estado nutricional, tanto crônicas como na restrição calórica quanto em situações como o jejum em animais e a privação de nutrientes em cultura de células foram demonstradas como sendo um dos principais fatores que podem ativar estes mecanismos de sinalização. Uma das formas em que esta interação entre a mitocôndria e a célula ocorre é através do manejo de Ca2+ mitocondrial, um processo em que sinais de Ca2+ gerados pela célula podem resultar em aumentos na [Ca2+] na matriz mitocondrial devido à presença do uniportador de Ca2+ mitocondrial na organelaEmbora o impacto do manejo de Ca2+ mitocondrial na função da célula tenha sido amplamente estudado, a regulação do processo de manejo de Ca2+ mitocondrial em si não é bem conhecida. Neste trabalho, nós nos propusemos a testar os efeitos de diferentes intervenções ligadas ao estado nutricional no manejo de Ca2+ mitocondrial e o possível impacto destas modulações nacapacidade de retenção e na taxa de captação de Ca2+ mitochondrial. As intervenções estudadas foram a restrição calórica, jejum e mudanças na dinâmica mitocondrial, e todas elas resultando em mudanças no manejo de Ca2+ mitocondrial, que foram medidos acompanhando a captação de Ca2+ em mitocôndrias isoladas ou células permeabilizadas utilizando a sonda Ca2+ Green 5N e em células intactas utilizando a sonda de Ca2+ citosólica Fura2-AM. Enquanto a restrição calórica resultou em uma maior capacidade de retenção de Ca2+ e em maiores taxas de captação, protegendo contra as condições patológicas de desregulação de Ca2+ observadas durante a isquemia/reperfusão, o jejum curto ou pela duração da noite resultou em uma diminuição na capacidade de retenção de Ca2+ e na oxidação fosforilativa mitocondriais. As mudanças observadas modulando a dinâmica mitocôndria (feitas utilizando-se mioblastos da linhagem C2C12) revelaram que mitocôndrias mais fragmentadas são menos capazes de captar Ca2+, enquanto mitocôndrias mais fusionadas possuem o fenótipo oposto. Essas mudanças no manejo de Ca2+ mitocondrial interferem com o processo de Store-Operated Ca2+ entry nestas células, demonstrando que essas modulações da captação de Ca2+ mitocondrial também podem ser relevantes em contextos fisiológicos. Em resumo, este trabalho ajudou a estabelecer novos mecanismos de modulação do manejo de Ca2+ mitocondrial que podem ser relevantes tanto em condições patológicas quanto na fisiologia normal das células

Músculo esquelético y lesión por reperfusión. ultraestructura, alteración y regeneración: revisión sistemática / Skeletal muscle and reperfusion injury: ultrastructure, disease and regeneration: systematic review

Introducción: La función tisular se basa en la asociación celular y la comunicación mediante uniones intercelulares o la matriz extracelular, que compone el tejido conectivo. La isquemia conlleva a cambios de lesión a los cuales las células responden según duración e intensidad del estímulo de lesión. En periodos cortos de isquemia y prolongados de reperfusión, el tejido muscular estriado esquelético presenta cambios en la predominancia de los tipos de fibras musculares y en los componentes de la matriz extracelular intramuscular. Objetivo: Establecer los cambios que se presentan en el músculo esquelético durante la reperfusión prolongada, tanto en las fibras musculares como en su matriz extracelular. Métodos: Se realizó una revisión sistemática mediante la búsqueda de artículos en inglés y español publicados en revistas indexadas en las bases de datos Ovid Medline, PubMed, Wiley y Science Direct. Los descriptores MESH utilizados fueron skeletal muscle, ischemia, reperfusion, fiber type fast twitch, fiber type slow twitch, sarcomere and myoblast. Se acoplaron los términos histology y tissue. Resultados: Se seleccionaron 81 publicaciones y se complementó con imágenes de músculos esqueléticos provenientes de muestras procesadas en el Laboratorio de Histología de la Universidad del Valle, Colombia. Conclusión: La recuperación del músculo durante la reperfusión seguida de isquemia, tiende hacia el patrón histológico y funcional normal. En algunos casos es un proceso lento y que aún después de varios meses no ha finalizado. Así mismo, pueden persistir alteraciones leves o moderadas en la contracción muscular, dados los cambios que se presentan en la matriz extracelular intramuscular.

Introduction: The tissue function is based on the cell association andcommunication through junctions or the extracellular matrix, which comprisesconnective tissue. Ischemia injury leads to changes to which the cells respondand it depends on duration and intensity of stimulus injury. In short periodsof prolonged ischemia and reperfusion, skeletal striated muscle tissue showschanges in the predominance of muscle fiber types and components of theextracellular matrix intramuscular. Objective: To determine the changes whichoccur in skeletal muscle during prolonged reperfusion in both muscle fibersin its extracellular matrix. Methods: A systematic review was performed bysearching for articles in English and Spanish published in journals indexed indatabases Ovid Medline, PubMed, Science Direct and Wiley. MeSH descriptorsused were skeletal muscle, ischemia, reperfusion, fast twitch fiber type, slowtwitch fiber type, sarcomere and myoblast. The terms tissue and histology werecoupled. Results: 81 relevant publications were selected and supplementedwith images of skeletal muscles from samples processed at the Laboratory ofHistology of the Universidad del Valle, Colombia. Conclusion: The recoveryof muscle during ischemia followed by reperfusion, tends toward the normalhistological and functional pattern. In some cases it is a slow process and evenafter several months has not been completed. Likewise, they may persist mildor moderate alterations in muscle contraction, given the changes that occur inthe intramuscular extracellular matrix.

Análise comparativa dos efeitos do ultrassom terapêutico e laser de baixa potência sobre a proliferação de células musculares durante a diferenciação celular / Comparative analysis between the effects of therapeutic ultrasound and low power laser on the proliferation of C2C12 myogenic precursor cells during cell differentiation

INTRODUÇÃO: Existe um grande interesse no estabelecimento de recursos e terapias a serem utilizados na tentativa de proporcionar um processo de reparo muscular de melhor qualidade e menor duração. O ultrassom terapêutico (US) e o laser de baixa potência (LBP) são recursos muito usados na prática clínica, porém são escassas, e por vezes contraditórias, as evidências científicas que determinam com segurança os parâmetros dosimétricos e metodológicos adequados. OBJETIVOS: O objetivo do estudo foi analisar o efeito do US e do LBP sobre a proliferação celular durante a diferenciação de mioblastos C2C12. MATERIAIS E MÉTODOS: Os mioblastos foram cultivados em meio de cultura de Eagle modificado por Dulbecco, contendo 10% de soro fetal bovino (SFB), sendo induzida a diferenciação pela adição de 2% de soro de cavalo durante 96 horas. Posteriormente, as células foram irradiadas com US pulsado a 20%, 3 MHz de frequência (intensidades de 0,2 e 0,5 W/cm², durante cinco minutos) ou submetidas ao tratamento com LBP (potência de saída de 10 mW, densidade de energia de 3 e 5 J/cm², por 20 segundos). A proliferação celular foi avaliada após 24h e 72h utilizando o método de MTT. Foram realizados três experimentos independentes, em cada condição citada e células não irradiadas serviram como controle. RESULTADOS: Os resultados obtidos foram submetidos à análise estatística utilizando a Análise de Variância (ANOVA), teste Dunnet, para verificar diferenças entre o grupo controle (não tratado) e os grupos tratados com US e LBP, adotando significância de p < 0,05. Os resultados evidenciaram que não houve diferença significativa na proliferação celular entre as células musculares submetidas a tratamento com ambos os recursos terapêuticos e as células controle, nos períodos de 24h e 72h após tratamento. Além disso, foi possível verificar que não houve aumento significativo no número de células após o período de 72h quando comparado a 24h, confirmando o processo de diferenciação celular, conforme esperado. CONCLUSÕES: Conclui-se que o US e o LBP, nos parâmetros avaliados, não alteraram a proliferação de mioblastos em processo de diferenciação.

INTRODUCTION: There is great interest in establishing resources and therapies to be used in an attempt to provide a process of muscle repair better and shorter. Two features commonly used to facilitate the healing process are the therapeutic ultrasound and laser power, however, are still scarce and sometimes contradictory scientific evidence to determine with certainty the parameters and methodology necessary to acquire these goals. OBJECTIVES: Thus, the objective of present study was to evaluate the effect of therapeutic ultrasound (US) and low level laser GaAlAs 660 nm on the proliferation of C2C12 myoblasts. MATERIALS AND METHODS: The myoblasts were cultivated in culture medium of Eagle modified by Dulbecco, containing 10% fetal bovine serum (FBS) and induced to differentiate by addition of 2% horse serum for 96h. Subsequently, cells were irradiated with US (20%, 3 MHz, and intensities of 0.2 and 0.5 W/cm² for five minutes) or with LLL (output power of 10 mW, density of 3 and 5 J/cm² for 20 seconds). The non-irradiated cells serve as controls. Three independent experiments were performed for each condition cited. Cell proliferation was evaluated after 24h and 72h using the MTT method. RESULTS: The results were statistically analyzed using analysis of variance (ANOVA/Dunnet) to verify differences between control cells (untreated) and US/LLL treated groups. The results showed no significant differences in viability and cell proliferation between LLL or US treated cells and control cells after 24h and 72h. Furthermore, it was observed no increase in the number of cells within the evaluation period after treatment, confirming the process of cell differentiation, as expected. RESULTS: In conclusion, US and the LLL, employed under the parameters described does not alter C2C12 proliferation.

Efecto cardíaco del extracto de epitelio pigmentado de la retina (melanina), del globo ocular de embrión de pollo “in vivo” e “in vitro” / Cardiac effect of the extract of retinal pigment epithelium (melanin) of the eyeball chick embryo

La melanina y su participación en la génesis de ciertas patologías cardíacas, ha sido revisada recientemente. Sin embargo, la expresión funcional y celular del efecto sobre el corazón no ha sido claramente establecida. En el presente trabajo se hizo uso del extracto de epitelio pigmentado de la retina del globo ocular de embrión de pollo, contentivo de melanina, para estudiar "in vivo" el patrón de contracción del corazón y la frecuencia cardíaca por videocardiograma, un método semi-invasivo en embriones de pollo de 3d-4d días de incubación, e "in vitro", su efecto sobre el patrón mitocondrial de mioblastos cardíacos en cultivo primario de Gota pendiente, incubados con el fluorocromo catiónico, 3,3´-dimetiloxicabonocianida (DiOC1 [3]). El tratamiento promovió una disfunción de la contracción peristáltica del corazón embrionario, con un incremento en el llenado auricular y una reducción de llenado ventricular durante las diástoles. Se determinó una reducción significativa de frecuencia cardíaca del 18,73 por ciento, luego de una hora de tratamiento. A diferencia de los controles, con un patrón homogéneo de fluorescencia verde emitido por las mitocondrias de forma alargada, la población de mioblastos tratados mostró un patrón de fluorescencia difusa, mitocondrias redondeadas y se observó la presencia de blebs a nivel de la superficie celular. Los resultados sugieren que el extracto de epitelio pigmentado de retina, contentivo de melanina, altera la contracción peristáltica e induce una reducción de la frecuencia cardíaca en modelo experimental de embrión de pollo, acompañada con un daño en las mitocondrias, probablemente vinculado a la activación de un proceso de muerte celular mediado por factores apoptoticos mitocondriales que podrían estar asociados a tales efectos

Melanin and its involvement in the genesis of certain cardiac diseases, has recently been revised. However, the expression of functional and cellular effects on the heart has not been clearly established. In this paper we made use of the extract of the retinal pigmented epithelium of the eyeball of the chick embryo, containing melanin, to study "in vivo" the pattern of contraction of the heart and the heart rate by Videocardiograma semi-invasive method in embryos of 3d-4d days of incubation, and in vitro, their effect on the pattern of mitochondrial using Hanging drop method, to primary culture of cardiac myoblasts, incubated with the cationic fluorochrome, 3,3-dimetiloxicabonocianida (DiOC1 [3]). The treatment promoted a malfunction of the peristaltic contraction of the embryonic heart, with an increase in atrial filling and reduced ventricular filling during diastole. We determined a significant reduction in heart rate of 18.73 percent, after an hour of treatment. The population of myoblasts showed a diffuse pattern of fluorescence, mitochondria were rounded and the cytoplasm showed the presence of blebs at the surface unlike controls with a uniform pattern of green fluorescence emitted by the elongated shape of mitochondria. The results suggested that the extract of retinal pigmented epithelium, melanin containing, alters the peristaltic contraction and decrease the heart rate in experimental model of chick embryo, together with mitochondrial damage, probably linked to the activation of a process of cell death mediated by factors apoptotic mitochondria, which could be associated with such effects

Stem cell, una alternativa al trasplante cardíaco en el tratamiento de la insuficiencia cardíaca / Stem cell, an alternative to heart transplant in the treatment of heart failure

El concepto tradicional mantenido por años sobre la incapacidad del corazón adulto para renovar sus células ha tenido que ser revisado ante la evidencia de los resultados obtenidos por numerosos estudios que demuestran la existencia en el corazón humano de células con capacidad proliferativa. El trasplante cardíaco aunque ha demostrado ser solución definitiva de la insuficiencia cardíaca no es aplicable a todos los pacientes, fundamentalmente por el déficit de donantes, los avances terapéuticos y quirúrgicos, si bien mejoran la calidad de vida, no son capaces de mejorar la contractilidad miocárdica ni sustituir el cardiomiocito. La terapia celular en la regeneración miocárdica surge como una de las estrategias terapéutica con un futuro prometedor en el tratamiento de la insuficiencia cardíaca, aunque no exenta de controversias, lo que obliga a un mayor conocimiento ante su aplicación clínica, lo cual no contrapone el iniciar ensayos clínicos que permitan un avance en esta dirección.

The traditional concept maintained for years on the incapacity of the adult heart to renew its cells had to be reviewed taking into account the results obtained by numerous studies that demonstrate the existence of cells with proliferative capacity in the human heart. Although the heart transplant has proved to be the definitive solution for heart failure, it may not be applied to all patients due mainly to the deficit of donors. The therapeutic and surgical advances improve the quality of life, but they cannot enhance the myocardial contractility, or replace the cardiomyocite. The cellular therapy in the myocardial regeneration appears as one of the strategical therapeutics with a promising future in the treatment of heart failure, even though it is not exempt from controversies that oblige to have a greater knowledge about its clinical application, but do not impede to start making clinical trials that allow to advance in this direction.