Terapia con células madre e insuficiencia cardiaca: aspectos éticos / Ethics of stem cell therapy for heart failure

Heart failure is one of the first diseases in which stem cells were used for regenerative medicine. Since 2001, many publications have shown that stem cell therapy has the potential to mitigate heart diseases, but there is no solid scientific evidence to fully support its clinical application at present. The future of regenerative medicine requires validated clinical trials with standardized platforms and transdisciplinary efforts to enable the development of safe and effective regenerative therapies to protect patients and to promote the ethical application of this new and highly promising therapy. Doctors and scientists have a responsibility to discuss with patients the current reality of regenerative therapies. They also have a responsibility to discourage the indiscriminate and commercial use of these therapies, which are sometimes based on false hopes, since their inappropriate use can harm vulnerable patients as well as research efforts. Although regenerative medicine may be the medicine of the future and might bring the hope of cure for chronic diseases, it is not yet ready for its wide clinical application.

Spermatogonial stem cells as a therapeutic alternative for fertility preservation of prepubertal boys / Espermatogônias-tronco como uma alternativa para a preservação da fertilidade de meninos pré-púberes

ABSTRACT Spermatogonial stem cells, which exist in the testicles since birth, are progenitors cells of male gametes. These cells are critical for the process of spermatogenesis, and not able to produce mature sperm cells before puberty due to their dependency of hormonal stimuli. This characteristic of the reproductive system limits the preservation of fertility only to males who are able to produce an ejaculate. This fact puts some light on the increase in survival rates of childhood cancer over the past decades because of improvements in the diagnosis and effective treatment in pediatric cancer patients. Therefore, we highlight one of the most important challenges concerning male fertility preservation that is the toxic effect of cancer therapy on reproductive function, especially the spermatogenesis. Currently, the experimental alternative for fertility preservation of prepubertal boys is the testicular tissue cryopreservationfor, for future isolation and spermatogonial stem cells transplantation, in order to restore the spermatogenesis. We present a brief review on isolation, characterization and culture conditions for the in vitro proliferation of spermatogonial stem cells, as well as the future perspectives as an alternative for fertility preservation in prepubertal boys. The possibility of restoring male fertility constitutes a research tool with an huge potential in basic and applied science. The development of these techniques may be a hope for the future of fertility preservation in cases that no other options exist, e.g, pediatric cancer patients.

RESUMO As espermatogônias-tronco, presentes nos testículos desde o nascimento, são as células progenitoras dos gametas masculinos, e, desse modo, críticas para o processo de espermatogênese. Antes da puberdade, essas células não são capazes de produzir espermatozoides maduros, o que só ocorrerá após o estímulo hormonal. Essa característica do sistema reprodutivo limita a possibilidade de preservação da fertilidade apenas para homens capazes de produzir um ejaculado. Tal fato coloca em evidência o aumento nas taxas de sobrevivência de crianças com câncer nas últimas décadas, devido principalmente à melhora no diagnóstico e ao tratamento dos pacientes pediátricos. Dessa forma, destaca-se um dos mais importantes desafios relativos à preservação da fertilidade masculina, que é o efeito tóxico das terapias anticâncer para o sistema reprodutivo, especialmente a espermatogênese. Tendo isso em vista, a alternativa experimental atualmente estudada para a preservação da fertilidade de pacientes pré-púberes é a criopreservação de tecido testicular para futuro isolamento e transplante de espermatogônias-tronco, a fim de restabelecer a espermatogênese. Apresentamos aqui uma breve revisão sobre isolamento, caracterização e condições de cultivo para a proliferação de espermatogônias-tronco, bem como as futuras perspectivas, como alternativa para preservação da fertilidade de meninos pré-púberes. A possibilidade de restabelecer a fertilidade masculina é uma ferramenta de pesquisa com potencial enorme de uso na pesquisa básica e aplicada. O desenvolvimento dessas técnicas pode fornecer uma esperança futura de preservação de fertilidade nos casos em que não há nenhuma outra opção, como para os pacientes pediátricos de câncer.

Current perspectives in stem cell therapy for spinal cord repair in humans: a review of work from the past 10 years / Atuais perspectivas da terapia com células tronco para regeneração medular em humanos: um revisão de trabalhos dos últimos 10 anos

Spinal cord injury (SCI) and amyotrophic laterals sclerosis (ALS) are devastating neurological conditions that affect individuals worldwide, significantly reducing quality of life, both for patients and their relatives. Objective : The present review aims to summarize the multiple restorative approaches being developed for spinal cord repair, the use of different stem cell types and the current knowledge regarding stem cell therapy. Method : Review of the literature from the past 10 years of human studies using stem cell transplantation as the main therapy, with or without adjuvant therapies. Conclusion : The current review offers an overview of the state of the art regarding spinal cord restoration, and serves as a starting point for future studies. .

Lesão medular (LM) e esclerose lateral amiotrófica (ELA) são condições devastadoras que acometem pessoas em todo o mundo, reduzindo a qualidade de vida tanto de pacientes como de entes queridos. Objetivo : A atual revisão tem como alvo as múltiplas abordagens restauradoras para a regeneração medular, o uso de diferentes tipos celulares e o atual conhecimento a cerca da terapia com células tronco. Método : Revisão de literatura dos últimos 10 anos usando transplantes de células tronco como estratégia principal, com ou sem terapia adjuvante, em humanos. Conclusão : A presente revisão oferece uma visão geral acerca da restauração medular e serve de ponto de partida para estudos futuros. .

Trasplante de tejido retiniano y de células progenitoras retinianas: una promesa terapéutica para pacientes con enfermedad de la retina / Retinal tissue transplantation and retinal progenitor cells: a therapeutic promise for patients with retinal disease

La retinopatía diabética, la degeneración macular relacionada con la edad y la retinitis pigmentosason las enfermedades retinianas más frecuentes en todo el mundo. A pesar de no contar consuficientes estudios que demuestren resultados funcionales positivos en cuanto a recuperar lafunción visual, el uso de células madre y células progenitoras retinianas y el trasplante de retinafetal parecen bastante promisorios. Hasta el momento no se han podido obtener resultadospositivos sobre la funcionalidad de las células trasplantadas, pero sí se ha demostrado que elprocedimiento para transferir el tejido retiniano es seguro y confiable. Aún no se ha intentadoen seres humanos el trasplante de células progenitoras retinianas, pero dicho trasplante ha dadoresultados satisfactorios en modelos múridos. Los estudios con células progenitoras retinianashan logrado demostrar en modelos múridos que se activan y expresan los fotorreceptores. Existenalgunas barreras de disponibilidad para el uso de células progenitoras retinianas, que se debensuperar con el fin de adelantar estudios que permitan aumentar las posibilidades de integracióny diferenciación de dichas células hacia fotorreceptores.

Retinal tissue transplantation and retinal progenitor cells: A therapeutic promise for patients with retinal diseaseWorldwide, diabetic retinopathy, age-related macular degeneration, and retinitis pigmentosahave the highest incidence rate among retinal diseases. Despite the lack of enough trialsdemonstrating positive functional results on eyesight recovery, the use of stem cells, retinalprogenitor cells, and fetal retinal tissue transplantation seem very promising. So far positiveresults on the functionality of the transplanted cells have not been obtained. However, the safetyand reliability of the procedure to transfer retinal tissue have been demonstrated. Transplantationof retinal progenitor cells has not been tried on human beings, but there have been satisfactory results with it in murine models. Trials with retinalprogenitor cells have demonstrated activation andexpression of photoreceptors in murine models. Somebarriers of availability exist for the use of retinalprogenitor cells that must be overcome in order tocarry out studies to increase the possibility of theirintegration and differentiation towards photoreceptors.

Stem cell through present and future.

Stem cell transplantation (SCT) has the potential to transform the lives of children with a wide variety of genetic diseases, ranging from inherent defects of hemopoietic cell production or function through to metabolic diseases mostly affecting solid organs. For these children life expectancy or quality of life would otherwise be very poor. It ranks as one of the most remarkable therapeutic advances of the past 40 years. Despite rapid technological improvements, however, there are still many short term risks and potential long term toxicities. Consequently, the rapid emergence of alternative therapies (including new drugs, enzyme and gene therapies), necessitate constant re-evaluation of the risk/benefit ratio for each disease and hence the appropriateness of SCT. This review describes the major aspects of the transplant process, indications for transplantation, outcome statistics, and areas where alternative therapies are becoming available. SCT remains a highly experimental therapy. Due to the relatively short history of the discipline no data exists on truly long term follow up. This is important as some organs benefit relatively poorly or problems may emerge which were never apparent as part of the untreated disease. The speed of technological change makes randomised trials on these diseases, which are individually quite rare, almost impossible to perform.

Potencial role of stem cell therapy in type 1 diabetes mellitus: [review]

Type 1 diabetes mellitus is the result of the autoimmune response against pancreatic beta-cell(s). At the time of clinical diagnosis near 70 percent of beta-cell mass is been destroyed as a consequence of the auto-destruction that begins months or even years before the clinical diagnosis. Although marked reduction of chronic complications was seen after development and progression of insulin therapy over the years for type 1 diabetic population, associated risks of chronic end-organ damage and hypoglycemia still remain. Besides tight glucose control, beta-cell mass preservation and/or increase are known to be other important targets in management of type 1 diabetes as long as it reduces chronic microvascular complications in the eyes, kidneys and nerves. Moreover, the larger the beta-cell mass, the lower the incidence of hypoglycemic events. In this article, we discuss some insights about beta-cell regeneration, the importance of regulation of the autoimmune process and what is being employed in human type 1 diabetes in regard to stem cell repertoire to promote regeneration and/or preservation of beta-cell mass.

O diabetes melito tipo 1 (DM1) é o resultado de uma resposta auto-imune contra as células-beta pancreáticas. Por ocasião do diagnóstico clínico do DM1, aproximadamente 70 por cento da massa de células-beta foram destruídas como conseqüência de uma autodestruição que se iniciou há anos ou meses antes dos primeiros sinais da doença. Embora a redução acentuada das complicações crônicas na população com DM1 foi observada após o desenvolvimento e evolução da insulinoterapia, os riscos associados às lesões dos órgãos-alvo e hipoglicemia persistem. Além do controle intensivo da glicemia, a preservação e/ou o aumento da massa de células-beta são reconhecidos como alvos importantes no tratamento do DM1. Isto vem associado à redução das complicações crônicas microvasculares na retina, rins e nervos e a menor incidência de eventos hipoglicêmicos. Neste artigo, discutimos alguns aspectos da regeneração das células-beta pancreáticas, a importância da regulação do processo auto-imune e o que está sendo empregado no DM1 humano com relação ao repertório das células-tronco nesse sentido.

Perspectivas no tratamento da perda auditiva com células-tronco / Perspectivas in the treatment of hearing loss with stem cells

Dano e perda de células ciliadas na orelha externa é a causa mais frequente de perda auditiva, desde que a perda das células ciliadas de mamíferos é irreversível. O tratamento de perda auditiva consiste o uso de aparelhos de amplificação sonora ou implante cocleares, porém ambos...

Damage and loss of hair cells in the inner ear is the most frequent cause of hearing loss, since mammalian hair cells are not replenishid once lost. The treatment of hearing loss consists of hearing aids or cochlear implants, but both...

Stem cells: proyecciones en ingeniería en tejido / Stem cells: tissue engineering projections

Células Madre o Stem Cells se definen como células con capacidad de clonación y auto renovación que se diferencian hacia múltiples linajes celulares. El término de totipotencialidad está reservado para aquellas Células Madre con capacidad ilimitada, que pueden dar origen a todos los tejidos diferenciados del cuerpo humano, junto a la placenta y membranas ovulares. Los términos multipotente y pluripotente son esencialmente sinónimos refiriéndose a la habilidad de diferenciarse hacia múltiples linajes celulares del organismo. Este proceso ha abierto una nueva alternativa terapéutica que se conoce como Ingeniería en Tejido la cual abre paso a la investigación, posibles vías terapéuticas de estudio, tales como la terapia celular, utilización de las células madre en la regeneración de tejido, aprovechando el proceso natural de renovación celular para reparar tejidos dañados o suplir algunos tejidos ausentes.

Stem cells in orthopedics: current concepts and possible future applications.

Stem cells are the cells that have the ability to divide for indefinite periods in culture and to give rise to specialized cells. Sources of these cells include embryo, umbilical cord and certain sites in adults such as the central nervous system [CNS] and bone marrow. Its use hold promise of wide spread applications particularly in areas of spinal cord injury, difficult non-unions, critical bone defects, spinal fusions, augmentation of ligament reconstructions, cartilage repair and degenerative disc disorders. This review article contains current information derived from Medline searches on the use in various orthopedic subspecialties. Some issues remain at the forefront of the controversy involving stem cell research - legislation, ethics and public opinion, cost and concentration methods. As is true with any new technology, the enthusiasm for this technology that has potential to influence virtually every orthopedic case management, must be balanced by subjecting it to stringent clinical and basic research investigations.

Células troncales en neurología / Stem Cells in neurology

Las investigaciones sobre células troncales han concitado creciente actividad en el campo de la investigación y publicaciones científicas. Nuestra revisión de la literatura expone qué es una célula troncal, sus propiedades, algunas de las estrategias para aislar y hacer proliferar células troncales neurales y los mecanismos moleculares involucrados en la integración funcional de estas células al cerebro receptor. Finalmente se comentan los posibles pasos de las futuras investigaciones, las que deberán identificar mejor las señales del receptor a las células donantes, así como descifrar con mayor profundidad la capacidad neurogénica del ambiente celular del cerebro adulto.

Neuronal stem cells.

Stem cells are self regenerating multipotential cells, found in the human brain which have the potential to differentiate into neurons, astrocytes and oligodendrocytes, and to self renew sufficiently to provide adequate number of cells in the brain. Neural stem cell grafts have been studied in a variety of animal models for various diseases like metabolic disorders, muscular dystrophies, neurodegenerative disorders, spinal cord repair, brain tumors and demyelinating disease. Stem cells may be derived from autologus, allogeneic or xenogenic sources. Histocompatibility is prerequisite for transplantation of allogeneic stem cells. Fetal tissue is the best current tissue source for human neural stem cells, however ethical issues are a major concern. Thus the prospect that stem cells could potentially be used to promote neurogenesis following injury and disease may seem attractive, yet the inherent problems associated with isolation and rejection in case of stem cells from another source, the potential to form tumors and ethical issues are the major challenges.