Eficacia del trasplante de células madre mesenquimales de lipoaspirado en el tratamiento de lesiones crónicas del manguito rotador. Modelo experimental en ratas / Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats

Antecedentes y objetivo: Las roturas del manguito rotador afectan aproximadamente al 30% de la población mayor de 60 años. El tratamiento quirúrgico por vía artroscópica de estas lesiones es el tratamiento de elección, sin embargo, a pesar de las mejoras técnicas de reparación el índice de rerroturas oscila entre el 11 y el 94%. Por ello, los investigadores buscan mejorar el proceso de curación biológica mediante el uso de diferentes alternativas como las células madre mesenquimales (MSC). Nuestro objetivo es evaluar la eficacia de un medicamento de terapia celular elaborado a partir de células madre alogénicas derivadas del tejido adiposo en un modelo de lesión crónica del manguito rotador en ratas. Material y método: Se creó la lesión del supraespinoso en 48 ratas para su posterior sutura a las 4 semanas. A 24 animales se les añadió las MSC en suspensión tras la sutura, y a 24 animales HypoThermosol-FRS® (HTS) como grupo control. En ambos grupos se analizó la histología (escala Åström y Rausing) y la carga máxima, desplazamiento y constante elástica del tendón supraespinoso a los 4 meses de la reparación. Resultados: No se encontraron diferencias estadísticamente significativas en la puntuación histológica comparando los tendones tratados con MSC con respecto a los tendones tratados con HTS (p=0,811) ni tampoco en los resultados de carga máxima (p=0,770), desplazamiento (p=0,852) ni constante elástica (p=0,669) del tendón en ambos grupos. Conclusiones: La adición en suspensión de células derivadas de tejido adiposo a la reparación de una lesión crónica de manguito no mejora las características histológicas ni biomecánicas del tendón suturado.(AU)

Background and aim: Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs). Our objective is to evaluate the efficacy of a Cellular Therapy Drug made from allogeneic stem cells derived from adipose tissue in a rat model of chronic rotator cuff injury. Material and methods: The supraspinatus lesion was created in 48 rats for subsequent suturing at 4 weeks. MSCs in suspension were added to 24 animals after suturing, and HypoThermosol-FRS® (HTS) to 24 animals as a control group. Histology (Åström and Rausing scale) and the maximum load, displacement and elastic constant of the supraspinatus tendon were analyzed in both groups 4 months after the repair. Results: No statistically significant differences were found in the histological score comparing the tendons treated with MSCs with respect to the tendons treated with HTS (P=.811) nor in the results of maximum load (P=.770), displacement (P=.852) or elastic constant (P=.669) of the tendon in both groups. Conclusions: The addition of adipose-derived cells in suspension to the repair of a chronic cuff injury does not improve the histology or biomechanics of the sutured tendon.(AU)

[Translated article] Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats / Eficacia del trasplante de células madre mesenquimales de lipoaspirado en el tratamiento de lesiones crónicas del manguito rotador. Modelo experimental en ratas

Antecedentes y objetivo: Las roturas del manguito rotador afectan aproximadamente al 30% de la población mayor de 60 años. El tratamiento quirúrgico por vía artroscópica de estas lesiones es el tratamiento de elección, sin embargo, a pesar de las mejoras técnicas de reparación el índice de rerroturas oscila entre el 11 y el 94%. Por ello, los investigadores buscan mejorar el proceso de curación biológica mediante el uso de diferentes alternativas como las células madre mesenquimales (MSC). Nuestro objetivo es evaluar la eficacia de un medicamento de terapia celular elaborado a partir de células madre alogénicas derivadas del tejido adiposo en un modelo de lesión crónica del manguito rotador en ratas. Material y método: Se creó la lesión del supraespinoso en 48 ratas para su posterior sutura a las 4 semanas. A 24 animales se les añadió las MSC en suspensión tras la sutura, y a 24 animales HypoThermosol-FRS® (HTS) como grupo control. En ambos grupos se analizó la histología (escala Åström y Rausing) y la carga máxima, desplazamiento y constante elástica del tendón supraespinoso a los 4 meses de la reparación. Resultados: No se encontraron diferencias estadísticamente significativas en la puntuación histológica comparando los tendones tratados con MSC con respecto a los tendones tratados con HTS (p=0,811) ni tampoco en los resultados de carga máxima (p=0,770), desplazamiento (p=0,852) ni constante elástica (p=0,669) del tendón en ambos grupos. Conclusiones: La adición en suspensión de células derivadas de tejido adiposo a la reparación de una lesión crónica de manguito no mejora las características histológicas ni biomecánicas del tendón suturado.(AU)

Background and aim: Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs). Our objective is to evaluate the efficacy of a Cellular Therapy Drug made from allogeneic stem cells derived from adipose tissue in a rat model of chronic rotator cuff injury. Material and methods: The supraspinatus lesion was created in 48 rats for subsequent suturing at 4 weeks. MSCs in suspension were added to 24 animals after suturing, and HypoThermosol-FRS® (HTS) to 24 animals as a control group. Histology (Åström and Rausing scale) and the maximum load, displacement and elastic constant of the supraspinatus tendon were analyzed in both groups 4 months after the repair. Results: No statistically significant differences were found in the histological score comparing the tendons treated with MSCs with respect to the tendons treated with HTS (P=.811) nor in the results of maximum load (P=.770), displacement (P=.852) or elastic constant (P=.669) of the tendon in both groups. Conclusions: The addition of adipose-derived cells in suspension to the repair of a chronic cuff injury does not improve the histology or biomechanics of the sutured tendon.(AU)

[Translated article] Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats.

BACKGROUND AND AIM: Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs). Our objective is to evaluate the efficacy of a cellular therapy drug made from allogeneic stem cells derived from adipose tissue in a rat model of chronic rotator cuff injury. MATERIAL AND METHODS: The supraspinatus lesion was created in 48 rats for subsequent suturing at 4 weeks. MSCs in suspension were added to 24 animals after suturing, and HypoThermosol-FRS® (HTS) to 24 animals as a control group. Histology (Åström and Rausing scale) and the maximum load, displacement and elastic constant of the supraspinatus tendon were analysed in both groups 4 months after the repair. RESULTS: No statistically significant differences were found in the histological score comparing the tendons treated with MSCs with respect to the tendons treated with HTS (P=0.811) nor in the results of maximum load (P=0.770), displacement (P=0.852) or elastic constant (P=0.669) of the tendon in both groups. CONCLUSIONS: The addition of adipose-derived cells in suspension to the repair of a chronic cuff injury does not improve the histology or biomechanics of the sutured tendon.

Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats. / Eficacia del trasplante de células madre mesenquimales de lipoaspirado en el tratamiento de lesiones crónicas del manguito rotador. Modelo experimental en ratas.

BACKGROUND AND AIM: Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs). Our objective is to evaluate the efficacy of a Cellular Therapy Drug made from allogeneic stem cells derived from adipose tissue in a rat model of chronic rotator cuff injury. MATERIAL AND METHODS: The supraspinatus lesion was created in 48 rats for subsequent suturing at 4 weeks. MSCs in suspension were added to 24 animals after suturing, and HypoThermosol-FRS® (HTS) to 24 animals as a control group. Histology (Åström and Rausing scale) and the maximum load, displacement and elastic constant of the supraspinatus tendon were analyzed in both groups 4 months after the repair. RESULTS: No statistically significant differences were found in the histological score comparing the tendons treated with MSCs with respect to the tendons treated with HTS (P=.811) nor in the results of maximum load (P=.770), displacement (P=.852) or elastic constant (P=.669) of the tendon in both groups. CONCLUSIONS: The addition of adipose-derived cells in suspension to the repair of a chronic cuff injury does not improve the histology or biomechanics of the sutured tendon.

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.

Las Células Madre Mesenquimales Endometriales modificadas genéticamente como Terapia Celular para la Endometriosis / Genetic modified endometrial mesenchymal stem cells as a cellular therapy for endometriosis

Se plantea una revisión e integración de tres conceptos fundamentales que son de alto interés científi-co y biomédico: la endometriosis, las Células Madre Mesenquimales Endometriales y su modificación genética para ser empleadas como terapia celular en esta patología. La endometriosis es una enferme-dad ginecológica, crónica y benigna caracterizada por la formación ectópica de estroma endometrial y glándulas principalmente en el peritoneo pélvico. Afecta entre el 6-15% de mujeres en edad reproducti-va con importantes consecuencias en su salud física, reproductiva y mental. Se ha planteado una importante participación de las células madre endometriales dentro de sus causas, por lo que se convierten en un objetivo terapéutico significativo. Se ha reportado múltiples características que establecen a las Células Madre Mesenquimales Endometriales como modelo idóneo para su utilización en terapia celular: caracterización definida, capacidad de migración y co-localización en la lesión, acción paracrina y juxtacrina, acción inmunomoduladora, acción moduladora de la angiogénesis y de la apop-tosis, baja tumorigenicidad, capacidad de transdiferenciación, entre otros, y se propone el uso concre-to de las células madre de sangre menstrual por su fácil obtención, caracterización y cultivo. (AU)

A review and integration of three fundamental concepts that are currently of high scientific and biome-dical interest is proposed: endometriosis, Endometrial Mesenchymal Stem Cells and their genetic modification to be used as cell therapy in this pathology. Endometriosis is a chronic, benign gynecolo-gical disease characterized by the ectopic formation of endometrial stroma and glands, mainly in the pelvic peritoneum. It affects between 6-15% of women in reproductive age with important consequen-ces on their physical, reproductive and mental health. It has been established an important participa-tion of endometrial stem cells within its causes, which is why they become a significant therapeutic target. It has been reported multiple characteristics that support Endometrial Mesenchymal Stem Cells as the optimal model for their use in cell therapy: defined characterization, migration capacity and co-location in the lesion, paracrine and juxtacrine action, immunomodulatory action, modulator action of angiogenesis and apoptosis, low tumorigenicity, transdifferentiation capacity, among others, and the specific use of menstrual blood stem cells is proposed because their easy obtaining, characteriza-tion and cell culture. It has been described that these stem cells have a dynamic and dual behavior, in the sense that they can contribute both to the formation of a lesion and to its modulation, for which, a better understanding of their activity is proposed before their direct use and, to mitigate this dynamic cellular behavior, it is proposed that cell therapy employ a strategy of genetic modification of cells for the expression of factors relevant to the treatment of endometriotic lesions and that have an antiproli-ferative, immunomodulatory action. (AU)

Terapia celular en enfermedades neurodegenerativas: una opción de tratamiento innovadora / Cell Therapy in Neurodegenerative Diseases: An Innovative Treatment Option

Introducción. Las enfermedades neurodegenerativas se caracterizan por la degeneración y pérdida de células nerviosas que conllevan trastornos de disfunción cognitiva y sensoriomotora, enfermedades tales como la esclerosis múltiple (EM) y la enfermedad de Párkinson (EP) entre otras. Recientemente, se ha reportado sobre resultados prometedores de la terapia celular con Células Madre Mesenquimales, células con la capacidad de diferenciarse en células del tejido nervioso, en el tratamiento de enfermedades neurodegenerativas. Objetivo. Evidenciar la utilidad de las células madre mesenquimales de médula ósea en el tratamiento de la esclerosis múltiple y enfermedad de Párkinson, como una posibilidad terapéutica en los tratamientos convencionales no favorables. Material y métodos. Estudio longitudinal prospectivo que consideró pacientes con EM (n=2) y EP (n=2), quienes como tratamiento coadyuvante recibieron células madre mesenquimales de médula ósea mediante método de trasplante autólogo. Resultados. Los pacientes recibieron entre 1 a 3 sesiones de reinfusión de células madre mesenquimales, cuyos seguimientos y evaluaciones periódicas reflejaron respuestas beneficiosas. Se observó mejoras representativas en las respectivas puntuaciones EDSS y UPDRS, así como, en la calidad de vida de los pacientes. Conclusiones . La terapia celular con células madre mesenquimales de médula ósea constituye una posibilidad terapéutica factible para las enfermedades neurodegenerativas como la EM y EP.

Introduction. Neurodegenerative disorders are characterized by a degeneration and loss of nerve cells leading to cognitive and sensorimotor dysfunction disorders, such as multiple sclerosis (MS) and Parkinson's disease (PD) among others. Recently, it has been reported promising results of cell therapy employing Mesenchymal Stem Cells, cells with the ability to differentiate into nervous tissue cells, in the treatment of neurological diseases. Objective. To expose the utility of bone marrow mesenchymal stem cells in the treatment of multiple sclerosis and Parkinson's disease, as a therapeutic option in unfavorable treatment outcomes. Material and methods. Prospective longitudinal study that included MS (n=2) and PD (n=2) patients, who received autologous transplantation of bone marrow mesenchymal stem cells as adjuvant treatment. Results. Patients received autologous MSC therapy from 1 to 3 reinfusions, follow-up and regular evaluations reflected beneficial responses. Representative improvements concerning patients' respectively EDSS or UPDRS scores, as well as in their quality of life were observed. Conclusions. Mesenchymal stem cells therapy constitutes a feasible therapeutic option for neurodegenerative disorders such as MS and PD.

Terapia celular en quemadura de segundo grado profundo: reporte de caso clínico / Cell therapy in deep second-degree burn wound: clinical case report

Se reporta el caso de un paciente pediátrico con quemaduras de segundo grado profundo en muslo derecho, con superficie corporal quemada del 8% por agua caliente, que recibió terapia celular como estrategia terapeútica alternativa. Tras procedimiento terapeútico con injertos de piel, se evidenció remanente una úlcera secundaria a quemadura (7 x 4 cm); por lo que, se procedió a valoración para terapia con células madres mesenquimales autólogas procedentes de médula ósea. Se realizó 8 sesiones de sembrado de células madre. La respuesta y evolución fueron favorables, la regeneración de tejidos se dio desde la profundidad hacia la superficie y desde el lateral a medial de la úlcera. Se evidenció revascularización y posterior epitelización de la zona afectada, sin secuelas de cicatrización.

Case report of a pediatric patient with deep second degree burn wounds on the right thigh, body surface area burnt 8% due to boiling water, who received cell therapy as an alternative therapeutic strategy. After a therapeutic procedure with skin grafts, a remaining burn wound (7 x 4 cm) was evidenced; consequently, an assessment for therapy using autologous mesenchymal stem cells derived from bone marrow was made. It was performed 8 sessions of somatic stem cells seeding. Results were favorable, tissue regeneration occurred from the depth to the surface, and from the lateral to medial side of the burn wound. Revascularization and subsequent epithelialization in the affected area were evidenced, without scarring repercussion.

Coautorias nas publicações brasileiras sobre medicina regenerativa: assimetrias na colaboração científica internacional / Brazilian co-authorships in regenerative medicine publications: inequalities in emerging countries scientific collaboration / Coautorías en las publicaciones brasileñas acerca de la medicina regenerativa: asimetrías en la colaboración científica internacional

A cooperação científica internacional tornou-se um fator essencial para que os países emergentes alcancem novos patamares de pesquisa, publicações e financiamento. No contexto de uma discussão analítica sobre a cooperação científica global, foram analisadas as publicações brasileiras indexadas na Web of Science e a coautoria entre pesquisadores locais e estrangeiros, com o objetivo de ilustrar as mudanças ocorridas na medicina regenerativa nas duas últimas décadas. O artigo conclui que, na última década, expandiu-se a coautoria entre autores brasileiros e destes com autores de países desenvolvidos, especialmente com aqueles dos Estados Unidos, mas também, em menor grau, com os de outros países emergentes e da América Latina. Pesquisadores brasileiros também publicaram artigos de impacto global, indicando a qualidade atingida, no país, pela pesquisa científica na área. A análise mostra que a colaboração abriu portas, no âmbito global, para a pesquisa local, mas também que as assimetrias científicas se mantiveram ao longo do tempo.

International scientific cooperation has become a key factor for emerging countries to improve research advancement, publication and funding. An analysis of local publications indexed in the Web of Science and co-authored between Brazilian researchers and non-residents was carried out, in the context of an analytical discussion on global scientific cooperation and with the aim of illustrating changes in the last two decades in regenerative medicine regarding this topic. The article concluded that in the last decade Brazil increased scientific co-authorships significantly domestically and with advanced country authors, especially with American authors, but also to a lesser degree with those of other emerging economies in and beyond Latin American. Local researchers have also published on their own several articles of global impact, revealing the academic quality attained in local sciences related to the area. Collaboration has undoubtedly opened doors for Brazilian regenerative medicine globally, but historical scientific inequalities remain.

La cooperación científica internacional se ha transformado en un factor sustancial para que los países emergentes progresen en investigación, publicación y financiación. Se desarrolló un análisis de publicaciones locales indexadas en la Web of Science y coautorías entre investigadores brasileños y extranjeros en el contexto de una reflexión sobre cooperación científica global y con el fin de ilustrar las modificaciones producidas en la medicina molecular regenerativa durante los dos últimos decenios. El artículo concluye que, en el último decenio, Brasil aumentó significativamente las coautorías domésticas y con autores de países avanzados, especialmente de los Estados Unidos, y en menor medida con aquellos de otras economías emergentes dentro y fuera de América Latina. Los investigadores locales han publicado varios artículos propios de impacto global, lo cual revela la calidad académica lograda, en Brasil, en el área. La colaboración ha abierto puertas en el mundo para la medicina regenerativa brasileña, pero las asimetrías científicas históricas persisten.

El negocio de la medicina regenerativa y las células madre: confusión con implicaciones legales / The regenerative medicine and stem cell business: confusion with legal implications

El auge de la medicina regenerativa y el crecimiento de la oferta de terapias autólogas obtenidas a partir de sangre, células o tejidos de los propios pacientes se ha visto favorecido por la actual disponibilidad de diversos dispositivos comerciales de fácil manejo que permiten la elaboración de los productos y su aplicación dentro de un mismo procedimiento. Independientemente de las dudosas eficacia y seguridad de muchos de los tratamientos que se ofrecen bajo el reclamo de las células madre o la medicina regenerativa, la mayor parte de los centros y de los profesionales que ofrecen estos tratamientos desconocen los requisitos y las implicaciones legales de su uso. Una confusión frecuente consiste en no distinguir entre la autorización que requiere el propio dispositivo, considerado producto sanitario, y la autorización para el uso del producto obtenido, que en general se trata de un medicamento, ya sea de terapia avanzada o no, o de un trasplante. Por otra parte, es frecuente que estos tratamientos tengan un carácter experimental, por lo que su administración en ese caso, además de requerir la evaluación ética correspondiente y la autorización de diversos organismos reguladores, debe ofrecerse de forma gratuita y tras recabar el consentimiento informado del paciente y contratar una póliza de seguros específica. En este artículo se presentan, de forma resumida, los principales requisitos para la aplicación de estos productos biológicos autólogos, con el objetivo de que puedan servir de guía tanto para los profesionales que los prescriben como para aquellos que inspeccionan los centros donde se administran. Por último, se ofrecen algunas recomendaciones para los pacientes. (AU)

The rise of regenerative medicine and the growth of the offer of autologous therapies, obtained from blood, cells or tissues of the patients, have been favoured by the current availability of an increasing number of commercial devices. Most of these devices are easy to use, allowing the elaboration of products and its application within the same procedure. Regardless of the questionable efficacy and safety of many of the treatments offered under the claim of stem cells or regenerative medicine, most of the centres and professionals offering these treatments are unaware of the legal requirements and implications of their use. A common confusion consists in not distinguishing between the authorization required by the equipment itself, considered a medical device, and the authorization for the use of the product obtained, usually considered a medicinal product (whether advanced therapy or not) or a transplant. Moreover, these treatments frequently have an experimental nature. In that case, in addition to requiring the corresponding ethical evaluation and the authorization of various regulatory bodies, their administration must be offered free of charge, obtaining the patient's informed consent and after contracting a specific insurance policy. In this article we present a brief summary of the main requirements for the application of these autologous biological products with the aim of serving as a guide both for the professionals who prescribe them and for those who inspect the centres where the products are administered. Finally, we include some recommendations for patients. (AU)

Empleo de células madre mononucleares en el tratamiento de osteoartritis en rodilla: caso de estudio en Cuba / Using Mononuclear Stem Cells for Osteoarthritis-Knee Treatments: A Case Study in Cuba / Uso de células-tronco mononucleares no tratamento da osteoartrite de joelho: estudo de caso em Cuba

Resumen Introducción: el desarrollo alcanzado en la medicina regenerativa posibilita el tratamiento de enfer medades incurables o que tienen una respuesta reducida a las terapéuticas actuales, así como la dis minución del consumo de medicamentos, en algunos casos. En Cuba, las especialidades de angiología y de ortopedia y traumatología son las que más han aplicado esta terapia. En el artículo se interpretan estadísticamente los resultados de la comparación, mediante STATGRAPHICS® Centurion XVI, de las varia bles controladas en dos tratamientos de osteoartritis en rodilla, uno empleando células madre mononucleares obtenidas de la sangre periférica y otro con la terapia convencional, para fundamentar la superioridad del nuevo tratamiento. Presentación del caso: se trataron 100 pacientes adultos atendidos en el Departamento de Ortopedia del Instituto de Hematología e Inmunología por osteoartrosis de rodilla, divididos en dos grupos. El grupo A (control) recibió el tratamiento convencional de infiltración con acetato de triamcinolona en la articulación afectada. El grupo B (estudio) recibió la implantación del concentrado de células mononucleares adultas hematopoyéticas por vía percutánea. Conclusión: se analizaron cada una de sus variables y se pudo comprobar que la mayoría de los datos recopilados no cumplía con una distribución normal, por lo que las siguientes pruebas se ejecutaron tomando como referencia la mediana de cada muestra. Se comparó entre la evaluación del dolor a la actividad y el consumo de medicamentos de cada uno de los grupos de tratamiento. Se evidenció la mejor respuesta de los pacientes para el tratamiento con células madre y una disminución en el consumo de fármacos.

Abstract Introduction: The development achieved in regenerative medicine has allowed the treatment of incurable diseases or those with a reduced response to current therapies, as well as cases with decreased consump tion of medicines. In Cuba, angiology, orthopedic, and traumatology specialists use this therapy the most. In this paper, we have presented the statistical analysis using the STATGRAPHICS® Centurion XVI for controlled variables in two osteoarthritis-knee treatments, one using mononuclear stem cells obtained from the peripheral blood and the other with a conventional therapy so as to demonstrate the superiority of the new treatment regime. Case report: A total of 100 adult patients treated in the Orthopedic Department at the Hematology and Immunology Institute for osteoarthritis-knee pains were studied. Group A (control) received the conventional treatment with triamcinolone acetate infiltration in the affected knee. Group B received the percutaneous implantation of the hematopoietic adult mononuclear cell concentrate. Conclusion: The analysis of each of the variables was performed to verify that most of the collected data did not comply with a normal distribution; hence, the following tests were performed taking the median of each sample as a reference. Comparisons were made between the evaluation of pain to the activity, as well as the consumption of drugs from each of the treatment groups. The best response of the patients was indicated for treatments with stem cells and a decrease in the consumption of drugs.

Resumo Introdução: o desenvolvimento alcançado na medicina regenerativa possibilita o tratamento de doenças incuráveis ou que têm uma resposta reduzida frente às terapias atuais, bem como a redução do consumo de medicamentos, em alguns casos. Em Cuba, as especialidades de angiologia e ortopedia e traumato logia são as que mais têm aplicado esta terapia. O estudo interpreta estatisticamente os resultados da comparação, por meio do STATGRAPHICS® Centurion XVI, das variáveis controladas em dois tratamentos de osteoartrite de joelho, sendo um utilizando células-tronco mononucleares obtidas de sangue periférico e outro com terapia convencional, com o objetivo de comprovar a superioridade do novo tratamento. Apresentação do caso: foram tratados 100 pacientes adultos atendidos no Departamento de Ortopedia do Instituto de Hematologia e Imunologia para osteoartrite de joelho, divididos em dois grupos. O grupo A (controle) recebeu tratamento convencional de infiltração com acetato de triancinolona na articulação afetada. O grupo B (estudo) recebeu implantação percutânea de concentrado de células mononucleares hematopoiéticas adultas. Conclusão: a análise de cada uma de suas variáveis foi realizada e constatou-se que a maioria dos dados coletados não obedecia a uma distribuição normal, de modo que os seguintes testes foram realizados tomando-se como referência a mediana de cada amostra. Foram feitas compara ções entre a avaliação da dor à atividade, bem como o consumo de medicamentos em cada um dos grupos de tratamento. Evidenciou-se uma melhor resposta dos pacientes ao tratamento com células-tronco e diminuição do consumo de medicamentos.

Cell therapy in the treatment of intervertebral disc degeneration / Terapia celular no tratamento da degeneração de disco intervertebral / Terapia celular en el tratamiento de la degeneración de disco intervertebral

ABSTRACT Approximately 80% of the world population experiences some type of back pain at some point in their life, and in 10% of this population the pain causes chronic disability resulting in a high cost for the treatment of these patients, in addition to compromising their work and social interaction abilities. Current treatment strategies include the surgical procedure for degenerated intervertebral disc resection, the nerve root block and physiotherapy. However, such treatments only relieve symptoms and do not prevent the degeneration of intervertebral discs. Therefore, new therapeutic strategies have emerged and include manipulating cells to recover the degenerated disc. This article will discuss the possible cell therapy alternatives used in the disc regeneration process, featuring a descriptive study of translational medicine that involves clinical aspects of new treatment alternatives and knowledge of basic research areas, such as cellular and molecular biology. Level of evidence V; Expert Opinion.

RESUMO Aproximadamente 80% da população mundial sofre algum tipo de dor nas costas em alguma fase de vida, sendo que em 10% dessa população, as dores acarretam incapacidade crônica, deflagrando alto custo de tratamento desses pacientes, além de comprometer as habilidades de trabalho e convívio social desses indivíduos. As estratégias de tratamento atuais incluem o procedimento cirúrgico por ressecção do disco intervertebral degenerado, bloqueio de raízes nervosas e fisioterapia. Entretanto, tais tratamentos apenas aliviam os sintomas e não impedem que ocorra a degeneração de discos intervertebrais. Portanto, novas estratégias terapêuticas têm surgido e incluem a manipulação de células com o objetivo de recuperar o disco degenerado. No presente artigo, serão discutidas as diferentes possibilidades alternativas de terapias celulares no processo de regeneração discal, caracterizando um estudo descritivo da medicina translacional que envolve aspectos clínicos de novas alternativas de tratamento e o conhecimento de áreas básicas de pesquisa como biologia celular e molecular. Nível de evidência V; Opinião do Especialista.

RESUMEN Aproximadamente 80% de la población mundial sufre algún tipo de dolor de espalda en alguna etapa de la vida, y en 10% de esa población, los dolores causan incapacidad crónica, deflagrando alto costo de tratamiento de esos pacientes, además de comprometer las habilidades laborales y convivencia social de esos individuos. Las estrategias de tratamiento actuales incluyen el procedimiento quirúrgico para la resección del disco intervertebral degenerado, bloqueo de las raíces nerviosas y fisioterapia. Entretanto, tales tratamientos solo alivian los síntomas y no impiden que ocurra la degeneración de discos intervertebrales. Por lo tanto, han surgido nuevas estrategias terapéuticas e incluyen la manipulación de células con el objetivo de recuperar el disco degenerado. En el presente artículo se discutirán las diferentes posibilidades alternativas de las terapias celulares en el proceso de regeneración discal, caracterizando un estudio descriptivo de la medicina traslacional que involucra aspectos clínicos de nuevas alternativas de tratamiento y conocimiento de áreas básicas de investigación como biología celular y molecular. Nivel de evidencia V; Opinión del especialista.

[The regenerative medicine and stem cell business: confusion with legal implications]. / El negocio de la medicina regenerativa y las células madre: confusión con implicaciones legales.

The rise of regenerative medicine and the growth of the offer of autologous therapies, obtained from blood, cells or tissues of the patients, have been favoured by the current availability of an increasing number of commercial devices. Most of these devices are easy to use, allowing the elaboration of products and its application within the same procedure. Regardless of the questionable efficacy and safety of many of the treatments offered under the claim of stem cells or regenerative medicine, most of the centres and professionals offering these treatments are unaware of the legal requirements and implications of their use. A common confusion consists in not distinguishing between the authorization required by the equipment itself, considered a medical device, and the authorization for the use of the product obtained, usually considered a medicinal product (whether advanced therapy or not) or a transplant. Moreover, these treatments frequently have an experimental nature. In that case, in addition to requiring the corresponding ethical evaluation and the authorization of various regulatory bodies, their administration must be offered free of charge, obtaining the patient's informed consent and after contracting a specific insurance policy. In this article we present a brief summary of the main requirements for the application of these autologous biological products with the aim of serving as a guide both for the professionals who prescribe them and for those who inspect the centres where the products are administered. Finally, we include some recommendations for patients.

ω-Conotoxina MVIIC e células-tronco mesenquimais promovem recuperação motora em ratos Wistar após trauma medular agudo / ω-Conotoxin MVIIC and mesenchymal stem cells promote motor recovery in Wistar rats after acute spinal cord injury]

O objetivo deste estudo foi avaliar o efeito da ω-conotoxina MVIIC e das células-tronco mesenquimais (CTM) de forma isolada e sua associação nos ratos submetidos ao trauma medular agudo (TMA). Trinta Rattus novergicus, linhagem Wistar, três meses de idade, foram distribuídos igualmente em cinco grupos experimentais: controle negativo (CN), controle positivo (CP), ω-conotoxina MVIIC (MVIIC), células-tronco mesenquimais da medula óssea (CTM-MO) e associação (MVIIC + CTM-MO). O grupo CN foi submetido à laminectomia sem trauma medular, e os grupos CP, MVIIC, CTM-MO e MVIIC + CTM-MO foram submetidos ao trauma medular contusivo. O grupo CP recebeu, uma hora após o TMA, 10µL de PBS estéril, e os grupos MVIIC e MVIIC + CTM-MO receberam 10µL de PBS contendo 20pmol da ω-conotoxina MVIIC, todos por via intratecal. Os grupos CTM-MO e MVIIC + CTM-MO receberam, 24 horas após, 1x106 de CTM via intravenosa. Avaliou-se a recuperação da função locomotora até o sétimo dia pós-trauma. Os animais tratados com MVIIC + CTM-MO obtiveram recuperação motora após o trauma medular agudo (P<0,05). Conclui-se que essa associação apresentou efeito neuroprotetor com melhora na função locomotora em ratos Wistar.(AU)

The objective of this study was to evaluate the effect of isolated ω-conotoxin MVIIC and mesenchymal stem cells (MSCs) and its association in rats submitted to acute spinal cord injury (SCI). Thirty Rattus norvegicus, Wistar strain, three-month-old rats were randomly distributed in five experimental groups with six animals: negative control (CN), positive control (CP), ω-conotoxin MVIIC (MVIIC), bone marrow mesenchymal stem cells (CTM-MO) and the association (MVIIC + CTM-MO). The CN group underwent laminectomy without spinal cord trauma, and groups CP, MVIIC, CTM-MO and MVIIC + CTM-MO were submitted to contusive spinal cord trauma. The CP group received 10µl of PBS one hour after SCI, and groups MVIIC and MVIIC + CTM-MO received 10µl of PBS containing 20pmol of ω-conotoxin MVIIC, both intrathecally. Groups CTM-MO and MVIIC + CTM-MO received 1x106 of MSCs intravenously 24 hours later. The recovery of locomotor function was evaluated up to seven days post-injury. The animals treated with MVIIC + CTM-MO obtained motor recovery after SCI (P<0.05). It is concluded that this association showed neuroprotective effect with improvements in locomotor function in Wistar rats.(AU)

Células madre/estromales mesenquimales. Su potencial terapéutico en medicina / Mesenchymal stem/stromal cells. Their therapeutic potential in medicine

Resumen La terapia celular y la medicina regenerativa son áreas en gran desarrollo en la investigación biomédica. En la mayoría de los tejidos existen mecanismos de auto-reparación llevados a cabo, principalmente, por células madre o progenitoras residentes con capacidad para diferenciarse y reemplazar a las células dañadas o para secretar factores tróficos que induzcan el proceso regenerativo. Dado que estos mecanismos de reparación no siempre son suficientes, se postula que la terapia celular puede contribuir a la regeneración de los tejidos sometidos a injuria. Las células madre/estromales mesenquimales (MSCs, del inglés Mesenchymal Stem/Stromal Cells) son un tipo de progenitor adulto multipotente, que tienen la capacidad de expandirse in vitro con facilidad cuando son aisladas de su nicho in vivo, migrar selectivamente a los tejidos lesionados, modular y evadir el sistema inmunológico, y secretar factores tróficos que ayudan a la reparación tisular. Asimismo, la fácil manipulación ex vivo permitiría también usarlas como vehículos de genes terapéuticos. Las principales fuentes de obtención son la médula ósea, el tejido adiposo y cordón umbilical. Los numerosos estudios pre-clínicos y clínicos han demostrado que las MSCs parecieran ser seguras tanto para uso autólogo como alogénico. En este trabajo se resumen las propiedades de las MSCs y su potencial terapéutico para una amplia gama de enfermedades, también presentamos los distintos ensayos clínicos avanzados que las posicionan en el ámbito biomédico como una herramienta interesante para la regeneración de tejidos y el tratamiento de enfermedades inflamatorias.

Abstract Cell therapy and regenerative medicine are currently active areas for biomedical research. In most tissues, there are self-repair mechanisms carried out mainly by resident stem cells that can differentiate and replace dead cells or secrete trophic factors that stimulate the regenerative process. These mechanisms often fail in degenerative diseases; thus it is postulated that exogenous cell therapy can contribute to tissue regeneration and repair. Mesenchymal stem cells (MSCs) are multipotent adult stem/progenitor cells, which could be easily expanded in vitro and have the ability to selectively migrate toward injured tissues, evade the immune system recognition, and secrete trophic factors to support tissue repair. Furthermore, MSCs could be engineered for the delivery of therapeutic genes. The main sources for MSCs are bone marrow, adipose tissue, and umbilical cord. A number of pre-clinical and clinical studies have shown that MSCs therapy is safe for both autologous and allogeneic uses. This review summarizes information about the properties of MSCs and their therapeutic potential for a broad spectrum of diseases. We also present here the last data about clinical trials that position the use of MSCs as an interesting tool for tissue regeneration and the treatment of inflammatory diseases.

Mesenchymal stromal cells represent a therapeutic option for systemic sclerosis patients / Células estromales mesenquimales representan una opción terapéutica en pacientes con esclerosis sistémica

ABSTRACT The mesenchymal stromal cells (MSCs) are hematopoietic stem cells with high capacity of differentiation to other cellular lineages, depending on the microenvironment in which they live as well as on the interaction and signaling pathways they establish with the extracellular matrix. Several properties have been described in these cells: proangiogenic, antifibrotic and immunomodulatory. These properties are being studied as a therapeutic approach for autoimmune diseases such as cutaneous systemic sclerosis (SSc). SSc is a systemic chronic disease, with an approximate prevalence of 35.6 cases per 100,000 inhabitants in North America and of 0.02% in Colombia in 2018. There are two different clinical variants, diffuse and localized. In both variants an important skin involvement and a rapidly deterioration of organs is present, which can overshadow the clinical prognosis and increase the mortality. Options for the treatment of advanced diffuse SSc are scarce mainly targeting symptomatic control with little impact on the progression and mortality. Therefore, there is an increasing interest in new therapies like advanced cellular therapy with hematopoietic stem cells and stromal mesenchymal cells. This article reviews the information related to the use of stromal mesenchymal cells in patients with this disease.

RESUMEN Las células mesenquimales estromales son células madre no hematopoyéticas pluripotenciales con alta capacidad de derivación a diferentes linajes celulares, dependiendo tanto del microambiente en el que se encuentren, como de la interacción y señalización que establezcan con la matriz extracelular del entorno, esto ha permitido describir un potencial proangiogénico, antifibrótico e inmunomodulador, que ha sido blanco de investigación en enfermedades autoinmunes como la esclerosis sistêmica cutánea. Considerando que la esclerosis sistêmica cutánea es una enfermedad inflamatoria crónica, con una prevalencia estimada de 35,6 casos por cada 100.000 habitantes en Norte América y de 0,02% en nuestro país para el 2018, se caracteriza por presentar dos variables clínicas principalmente; una variante limitada y una variante difusa, presentando en ambas un compromiso extenso de piel y órganos que puede ser rápidamente progresivo y deteriorar el pronóstico de los pacientes que la padecen aumentando su mortalidad. Debido a que las opciones terapéuticas en esta entidad son limitadas y buscan únicamente el control de síntomas, pero con poco impacto en progresión y mortalidad, terapias celulares avanzadas han surgido como nuevas opciones terapéuticas incluyendo el trasplante de células madre hematopoyéticas y las células mesenquimales estromales. A continuación, se revisará acerca de la utilidad y evidencia de células mesenquimales estromales en pacientes con esta enfermedad.

Enquadramentos na medicina regenerativa: os relatos recentes na imprensa brasileira / Frames in regenerative medicine: recent news in the Brazilian press / Marcos referenciales de la medicina regenerativa: noticias recientes en la prensa brasileña

A mídia funciona como uma ponte entre a medicina e o público, e impacta como a informação é organizada e apresentada às pessoas. Realizou-se uma análise de conteúdo, quantitativo e qualitativo, dos enquadramentos principais nas matérias sobre medicina regenerativa publicadas pela Folha de São Paulo e O Globo, entre janeiro de 2012 e maio do 2019. A análise mostrou algumas limitações nas informações publicadas: um número bastante escasso de relatos, com poucas matérias sobre controvérsias sociais e regulatórias e matérias de tons otimistas demais sobre os benefícios das terapias celulares. Conclui-se que falta uma contribuição mais sistemática da imprensa à legitimação social e institucional desta área de ponta no país, desenvolvida com recursos públicos e que oferece uma oportunidade imperdível no aumento da consciência em saúde coletiva, assim como, na participação competitiva do Brasil no cenário global.

Mass media works as a bridge between medicine and the public and produces an impact according to how information is organized and presented. A quantitative and qualitative content analysis was developed on the main framings on regenerative medicine found in reports by the newspapers Folha de São Paulo and O Globo between January 2012 and May 2019. The analysis found limitations in the information published: a reduced number of stories, the presence of few articles on social and regulatory controversies and a portrayal of over-optimistic accounts on the benefits of cellular-based therapies. The article concludes that there is a lack of a more systematic contribution of the printed press to the social and institutional legitimation of the local area, one developed with public resources and that offers a valuable opportunity to raise awareness on collective health, as well as, for a competitive inclusion of Brazil at the global level.

Los medios de comunicación masiva funcionan como un puente entre la medicina y el público, e impactan en los públicos según cómo la información sea organizada y presentada. Se realizó un análisis de contenido, cuantitativo y cualitativo, de los encuadramientos principales en los diarios: Folha de S.Paulo y O Globo sobre la medicina regenerativa entre enero de 2012 y mayo de 2019. El análisis demostró las limitaciones de los contenidos: um número bastante escaso de reportajes, pocas noticias sobre debates y controversias sociales y de tono demasiado optimista acerca de los beneficios de las terapias celulares. Se concluye que falta una contribución sistemática de la prensa a la legitimación social e institucional de esta área de punta em el país, desarrollada com recursos públicos y que ofrece una valiosa oportunidad para un aumento de conciencia sobre la salud colectiva y una participación competitiva de Brazil en el escenario global.

Células madre adiposas humanas disminuyen el daño de la fibrosis hepática con baja persistencia de células trasplantadas en ratas / Human adipose stem cells decrease liver fibrosis damage with low persistence of transplanted cells in rats

RESUMEN: En la enfermedad hepática crónica el trasplante ortotópico es la única alternativa terapéutica actual pero es limitada por falta de donantes. Ensayos con células madre adultas en daño hepático agudo evidencian promisorios resultados. El objetivo de este trabajo fue evaluar en ratas con daño hepático crónico la efectividad de la infusión de células madre adiposas humanas (CMAd-h). Ratas con fibrosis hepática inducida por tioacetamida fueron agrupadas en: grupo I control que no recibió tioacetamida ni células madre, grupo II recibió tioacetamida y suero fisiológico i.v., grupo III recibió tioacetamida y células madre adiposas 1 x 106/kg i.v. vía vena de la cola. La regeneración hepática histológica se evaluó por el index METAVIR, mientras las Macrophagocytus stellatus, células estrelladas a- SMA+ y células colágeno I+ por inmunohistoquímica; el daño funcional se evaluó por los niveles sanguíneos de los analitos Aspartato Aminotransferasa (AST), Alanina Aminotransferasa (ALT), Fosfatasa Alcalina (ALP), úrea y nitrógeno ureico (BUN) y hemograma. Los resultados muestran atenuación del daño estructural hepático evidenciado por disminución de los nódulos, del grado de lesión histológica en el score Metavir, y disminución de Macrophagocytus stellatus, células a-SMA+ y células colágeno tipo I+; funcionalmente hay reducción moderada de AST, ALT, urea, BUN y disminución moderada de células blancas pero efecto favorable sobre el volumen corpuscular media y la hemoglobina corpuscular media. Ocho semanas después de la infusión hay escasa población de CMAd-h en el hígado. En conclusión la infusión intravenosa de CMAd-h en ratas disminuye el daño funcional y estructural de la fibrosis hepática con escasa persistencia de CMAd-h en el parénquima hepático. A nuestro conocimiento este es el primer trabajo que evalúa el efecto de las CMAd-h en el modelo daño hepático crónico murino y la persistencia de las células trasplantadas.

SUMMARY: In chronic liver disease, orthotopic transplantation is the only current therapeutic alternative but it is limited due to lack of donors. Trials with adult stem cells in acute liver damage show promising results. The aim of this work was to evaluate the effectiveness of human adipose stem cell (h-ASC) infusion in rats with chronic liver damage. Rats with thioacetamide- induced liver fibrosis were grouped into: group I control that did not receive thioacetamide and h-ASC, group II received thioacetamide and saline i.v., group III received thioacetamide and h-ASC 1 x 106/ kg i.v. via tail vein. Histological liver regeneration was evaluated by METAVIR index, while Macrophagocytus stellatus (Kupffer cells), stellate cells a-SMA+ and collagen I+ cells by immunohistochemistry; functional damage was evaluated by blood levels of the analytes Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Urea and Blood Urea Nitrogen (BUN) and hemogram. The results show attenuation of structural liver damage evidenced by decreased nodules, degree of histologic injury on Metavir score, and decreased Macrophagocytus stellatus, a-SMA+ cells and type I+ collagen cells; functionally there is moderate reduction of AST, ALT, urea, BUN and moderate decrease of white cells but favorable effect on mean corpuscular volume and mean corpuscular hemoglobin. Eight weeks after infusion there is a small population of h-ASC in the liver. In conclusion, intravenous infusion of h-ASC in rats reduces functional and structural damage of hepatic fibrosis with low persistence of h- ASC in the liver parenchyma. To our knowledge this is the first work that evaluates the effect of h-SC in the model of chronic murine liver damage and the persistence of transplanted cells.

Células madre como alternativa al marcapaso transvenoso / Stem cells as an alternative to the transvenous pacemaker

Resumen Objetivo: describir el estado del arte del marcapasos biológico y las perspectivas para crear tejido cardíaco de marcapasos utilizando modernas tecnologías genéticas y de ingeniería de tejidos. Métodos: revisión sistemática de la literatura. Resultados: los marcapasos se han convertido en el tratamiento primordial para cierto tipo de arritmias o bloqueos avanzados sintomáticos. Somos testigos de mejoras continuas en la tecnología del dispositivo, con avances en el diseño del cable, el tamaño del generador, la longevidad de la batería y los algoritmos de software que se han traducido en dispositivos más pequeños con funcionalidad mejorada. En la actualidad existen muchos sistemas implantables de cardioestimulación capaces de reemplazar la función de los marcapasos fisiológicos (seno y nódulos aurículo-ventriculares) que incluyen los recientemente desarrollados marcapasos secuenciales y autoprogramables. En la última década la investigación ha confirmado que el marcapasos biológico se puede crear mediante la terapia génica y la terapia celular. Hoy existen dos enfoques para construir marcapasos biológicos: uno es para introducir genes de marcapasos en células madre mesenquimales, y el otro es para inducir células madre pluripotentes en las células del nódulo sinoauricular. Conclusiones: los marcapasos biológicos, actualmente en la etapa preclínica, podrían ser una alternativa a los dispositivos electrónicos para pacientes seleccionados en el futuro.

Abstract Objective: To describe the state of the art of biological pacemakers and the perspectives for creating cardiac pacing tissue using modern genetic and tissue engineering technologies. Methods: A systematic review of the literature. Results: Pacemakers have become the first line treatment for certain types of arrhythmias and advanced symptomatic blocks. We are witnessing continuous improvements in the technology of the device, with advances in the design of the cable, the size of the generator, the longevity of the battery, as well as the software algorithms that have led to smaller devices with improved functions. There are currently many cardiac stimulation implantable systems capable of replacing the function of physiological pacemakers systems (sinus and atrial-ventricular nodes) that include the recently developed sequential and self-programmable pacemakers. In the last ten years or so, studies have confirmed that biological pacemakers can be created using gene therapy and cell therapy. There are currently to main efforts to construct biological pacemakers. One is to introduce pacemaker genes in mesenchymal stem cells, and the other is to introduce pluripotent stem cells in cells of the sinoatrial node. Conclusions: Biological pacemakers, currently in the pre-clinical stage, could be an alternative to the electronic devices for selected patients in the future.