RESUMO
ABSTRACT Degenerative retinal diseases such as retinitis pigmentosa, Stargardt's macular dystrophy, and age-related macular degeneration are characterized by irreversible loss of vision due to direct or indirect photoreceptor damage. No effective treatments exist, but stem cell studies have shown promising results. Our aim with this review was to describe the types of stem cells that are under study, their effects, and the main clinical trials involving them.
RESUMO As doenças degenerativas da retina, como retinose pigmentar, distrofia macular de Stargardt e degeneração macular relaciona à idade, são caracterizadas por perda irre versível da visão devido a danos diretos ou indiretos aos fotorreceptores. Não existem tratamentos eficazes, porém os estudos com células-tronco mostraram resultados promissores. Nosso objetivo com esta revisão foi descrever os tipos de células-tronco em estudo, seus efeitos e os principais ensaios clínicos que as envolvem.
Assuntos
Humanos , Degeneração Retiniana/terapia , Células-Tronco Pluripotentes/transplante , Transplante de Células-Tronco/métodos , Retina/citologia , Ensaios Clínicos como Assunto , Resultado do TratamentoRESUMO
Degenerative retinal diseases such as retinitis pigmentosa, Stargardt's macular dystrophy, and age-related macular degeneration are characterized by irreversible loss of vision due to direct or indirect photoreceptor damage. No effective treatments exist, but stem cell studies have shown promising results. Our aim with this review was to describe the types of stem cells that are under study, their effects, and the main clinical trials involving them.
Assuntos
Células-Tronco Pluripotentes/transplante , Degeneração Retiniana/terapia , Transplante de Células-Tronco/métodos , Ensaios Clínicos como Assunto , Humanos , Retina/citologia , Resultado do TratamentoRESUMO
INTRODUCTION AND AIMS: Fecal incontinence is a disabling condition with devastating consequences for the patients. Medical and surgical options are not very satisfactory, reason by which regenerative medicine has been considered in this field. In the present research, we analyzed functional and histologic effects after implanting pluripotent stem cells (PSCs) in a murine model with sphincterotomy. MATERIALS AND METHODS: Female Wistar rats were subjected to sphincterotomy and divided into three groups. Group 1 (control group) was treated with 300µL of balanced saline solution and group 2 (late treatment) and group 3 (early treatment) received 50,000 PSCs resuspended in 300µL of balanced saline solution. All animals were evaluated through high-resolution anorectal manometry 24hours before and after sphincterotomy and every month for three months. Finally, the rats were euthanized and histopathologic sections from the anal canal were obtained. RESULTS: All groups showed a decrease in resting anal pressure and squeeze anal pressure 24hours after sphincterotomy. At the third month, higher anal pressures in the groups treated with PSCs were detected. Regarding the histologic effects, the microscopic architecture was restored and there was a significant decrease in the inflammatory response in the groups treated with PSCs. CONCLUSION: PSCs implantation improves anal tone, as well as histologic structure, presenting better regenerative results when implanted as early treatment.
Assuntos
Canal Anal/cirurgia , Incontinência Fecal/terapia , Células-Tronco Pluripotentes/transplante , Complicações Pós-Operatórias/terapia , Esfincterotomia/efeitos adversos , Canal Anal/fisiopatologia , Animais , Incontinência Fecal/etiologia , Incontinência Fecal/fisiopatologia , Feminino , Manometria , Ratos , Ratos Wistar , Regeneração , Resultado do TratamentoRESUMO
During the past decade, several types of stem cells have been investigated as promising therapeutic agents for cardiovascular diseases (CVDs). Among them, mesenchymal stem cells (MSCs) were the most investigated stem cell population. Hundreds of clinical trials later, results remain disappointing and far from the revolutionary improvements expected for heart function. In the present review, we address strategies under investigation to boost MSC therapy for CVDs. Pluripotent stem cells (PSCs) are also intended to reach clinical applications for CVDs, but here we suggest that, in the short term, the major impact of PSCs in the cardiovascular field might be at the bench and not the bedside.
Assuntos
Doenças Cardiovasculares/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Pluripotentes/transplante , Animais , Doenças Cardiovasculares/fisiopatologia , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Pluripotentes/citologiaRESUMO
Despite decades of research, no compelling non-surgical therapies have been developed for foetal hydrocephalus. So far, most efforts have pointed to repairing disturbances in the cerebrospinal fluid (CSF) flow and to avoid further brain damage. There are no reports trying to prevent or diminish abnormalities in brain development which are inseparably associated with hydrocephalus. A key problem in the treatment of hydrocephalus is the blood-brain barrier that restricts the access to the brain for therapeutic compounds or systemically grafted cells. Recent investigations have started to open an avenue for the development of a cell therapy for foetal-onset hydrocephalus. Potential cells to be used for brain grafting include: (1) pluripotential neural stem cells; (2) mesenchymal stem cells; (3) genetically-engineered stem cells; (4) choroid plexus cells and (5) subcommissural organ cells. Expected outcomes are a proper microenvironment for the embryonic neurogenic niche and, consequent normal brain development.
Assuntos
Barreira Hematoencefálica/cirurgia , Líquido Cefalorraquidiano/fisiologia , Hidrocefalia/cirurgia , Células-Tronco Pluripotentes/transplante , Animais , Plexo Corióideo/citologia , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologiaRESUMO
Adult mesenchymal stromal cell-based interventions have shown promising results in a broad range of diseases. However, their use has faced limited effectiveness owing to the low survival rates and susceptibility to environmental stress on transplantation. We describe the cellular and molecular characteristics of multilineage-differentiating stress-enduring (Muse) cells derived from adipose tissue (AT), a subpopulation of pluripotent stem cells isolated from human lipoaspirates. Muse-AT cells were efficiently obtained using a simple, fast, and affordable procedure, avoiding cell sorting and genetic manipulation methods. Muse-AT cells isolated under severe cellular stress, expressed pluripotency stem cell markers and spontaneously differentiated into the three germ lineages. Muse-AT cells grown as spheroids have a limited proliferation rate, a diameter of â¼15 µm, and ultrastructural organization similar to that of embryonic stem cells. Muse-AT cells evidenced high stage-specific embryonic antigen-3 (SSEA-3) expression (â¼60% of cells) after 7-10 days growing in suspension and did not form teratomas when injected into immunodeficient mice. SSEA-3+ -Muse-AT cells expressed CD105, CD29, CD73, human leukocyte antigen (HLA) class I, CD44, and CD90 and low levels of HLA class II, CD45, and CD34. Using lipopolysaccharide-stimulated macrophages and antigen-challenged T-cell assays, we have shown that Muse-AT cells have anti-inflammatory activities downregulating the secretion of proinflammatory cytokines, such as interferon-γ and tumor necrosis factor-α. Muse-AT cells spontaneously gained transforming growth factor-ß1 expression that, in a phosphorylated SMAD2-dependent manner, might prove pivotal in their observed immunoregulatory activity through decreased expression of T-box transcription factor in T cells. Collectively, the present study has demonstrated the feasibility and efficiency of obtaining Muse-AT cells that can potentially be harnessed as immunoregulators to treat immune-related disorders. Stem Cells Translational Medicine 2017;6:161-173.
Assuntos
Tecido Adiposo/patologia , Carcinogênese/patologia , Imunomodulação , Células-Tronco Pluripotentes/citologia , Fator de Crescimento Transformador beta1/farmacologia , Animais , Biomarcadores/metabolismo , Carcinogênese/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Camadas Germinativas/citologia , Humanos , Imunomodulação/efeitos dos fármacos , Cariótipo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fosforilação/efeitos dos fármacos , Células-Tronco Pluripotentes/transplante , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Baço/citologia , Estresse Fisiológico , Teratoma/patologiaRESUMO
Parkinson's disease (PD) is a neurodegenerative disorder, whose cardinal pathology is the loss of dopaminergic neurons in the substantia nigra. Current treatments for PD have side effects in the long term and do not halt disease progression or regenerate dopaminergic cell loss. Attempts to compensate neuronal cell loss by transplantation of dopamine-producing cells started more than 30 years ago, leading to several clinical trials. These trials showed safety and variable efficacy among patients. In addition to variability in efficacy, several patients developed graft-induced dyskinesia. Nevertheless, they have provided a proof of concept that motor symptoms could be improved by cell transplantation. Cell transplantation in the brain presents several immunological challenges. The adaptive immune response should be abolished to avoid graft rejection by the host. In addition, the innate immune response will always be present after transplanting cells into the brain. Remarkably, the innate immune response can have dramatic effects on the survival, differentiation and proliferation of the transplanted cells, but has been hardly investigated. In this review, we analyze data on the functional effects of signals from the innate immune system on dopaminergic differentiation, survival and proliferation. Then, we discussed efforts on cell transplantation in animal models and PD patients, highlighting the immune response and the immunomodulatory treatment strategies performed. The analysis of the available data lead us to conclude that the modulation of the innate immune response after transplantation can increase the success of future clinical trials in PD by enhancing cell differentiation and survival. This article is part of a Special Issue entitled SI: PSC and the brain.
Assuntos
Neurônios Dopaminérgicos/patologia , Neurônios Dopaminérgicos/fisiologia , Células-Tronco Neurais/imunologia , Células-Tronco Neurais/transplante , Doença de Parkinson/imunologia , Doença de Parkinson/terapia , Animais , Diferenciação Celular/fisiologia , Células-Tronco Embrionárias/fisiologia , Células-Tronco Embrionárias/transplante , Humanos , Células-Tronco Neurais/patologia , Doença de Parkinson/patologia , Células-Tronco Pluripotentes/fisiologia , Células-Tronco Pluripotentes/transplante , Transplante de Células-Tronco/métodosRESUMO
Regenerative medicine is a medical multidisciplinary area with the aim of morphologic and functional restoration of tissues or organs in order to re-establish normal function. The main bases of regenerative medicine are the use of autologous stem or progenitor cells and the ex vivo construction of physical-mechanical tissue structuring organization, which with stem cells may form bioartificial organs. Another eventual strategy is in vivo stem or progenitor cell stimulation for proliferation. Tissue engineering entirely combines the use of cells, biochemical and physicochemical factors, nanomaterials and bioengineering methods to improve or replace biological functions of tissues and organs. The progressive understanding of the proliferation and differentiation of the process of stem cells and their in vitro manipulation has been the launching platform for the field of regenerative medicine. In this review we describe the main strategies used for regenerative medicine in tissue regeneration along with the main obtained clinicalsurgical benefits.
La medicina regenerativa es una área multidisciplinaria destinada a la recuperación morfológica y funcional de tejidos y órganos severamente lesionados. Los principales recursos que emplea la medicina regenerativa son: células madre o troncales autólogas, y moldes estructurales de soporte físico-mecánico tisular construidos ex vivo, que pueden formar órganos bioartificiales; otra posibilidad es la estimulación de células madre in vivo para su proliferación. La ingeniería tisular combina, integralmente, el uso de células, factores bioquímicos y físicos, nanomateriales y métodos de bioingeniería para mejorar o remplazar las funciones biológicas de tejidos y órganos. El entendimiento progresivo de los procesos de proliferación y diferenciación celulares, y la manipulación in vitro de las células madre, ha sido la plataforma del desarrollo de la medicina regenerativa. En esta revisión se describen las diferentes estrategias que utiliza la medicina regenerativa en la regeneración de tejidos, y los principales beneficios clínico-quirúrgicos conseguidos con su aplicación.
Assuntos
Nanomedicina/métodos , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Derme Acelular , Órgãos Bioartificiais , Produtos Biológicos/uso terapêutico , Diferenciação Celular , Matriz Extracelular/química , Previsões , Humanos , Células-Tronco Pluripotentes Induzidas/transplante , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Nanomedicina/tendências , Nanoestruturas , Células-Tronco Pluripotentes/transplante , Próteses e Implantes , Medicina Regenerativa/tendências , Telas Cirúrgicas , Engenharia Tecidual/tendênciasRESUMO
Tissue engineering currently constitutes a complex, multidisciplinary field exploring ideal sources of cells in combination with scaffolds or delivery systems in order to form a new, functional organ to replace native organ lack or loss. Short bowel syndrome (SBS) is a life-threatening condition with high morbidity and mortality rates in children. Current therapeutic strategies consist of costly and risky allotransplants that demand lifelong immunosuppression. A promising alternative is the implantation of autologous organoid units (OU) to create a tissue-engineered small intestine (TESI). This strategy is proven to be stem cell and mesenchyme dependent. Intestinal stem cells (ISCs) are located at the base of the crypt and are responsible for repopulating the cycling mucosa up to the villus tip. The stem cell niche governs the biology of ISCs and, together with the rest of the epithelium, communicates with the underlying mesenchyme to sustain intestinal homeostasis. Biopharmaceuticals are broadly used in the clinic to activate or enhance known signaling pathways and may greatly contribute to the development of a full-thickness intestine by increasing mucosal surface area, improving blood supply, and determining stem cell fate. This review will focus on tissue engineering as a means of building the new small intestine, highlighting the importance of stem cells and recombinant peptide growth factors as biopharmaceuticals.
Assuntos
Regeneração Tecidual Guiada/métodos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Intestino Delgado/cirurgia , Células-Tronco Pluripotentes/transplante , Proteínas Recombinantes/uso terapêutico , Síndrome do Intestino Curto/cirurgia , Engenharia Tecidual/métodos , Humanos , Técnicas de Cultura de Órgãos , Organoides/transplante , Alicerces TeciduaisRESUMO
Transgenic technology has become an essential tool for the development of animal biotechnologies, and animal cloning through somatic cell nuclear transfer (SCNT) enabled the generation of genetically modified animals utilizing previously modified and selected cell lineages as nuclei donors, assuring therefore the generation of homogeneous herds expressing the desired modification. The present study aimed to discuss the use of SCNT as an important methodology for the production of transgenic herds, and also some recent insights on genetic modification of nuclei donors and possible effects of gene induction of pluripotency on SCNT.
Tecnologias de modificação genética têm se tornado ferramentas essenciais para o desenvolvimento de biotecnologias animais. A clonagem animal mediante transferência nuclear de célula somática (TNCS) possibilitou a geração de animais geneticamente modificados através da utilização de linhagens celulares previamente modificadas e selecionadas como doadoras de núcleo, garantindo desta maneira a geração de rebanhos homogênoes expressando a modificação desejada. O presente estudo objetivou discutir o uso da TNCS como importante metodologia para a produção de rebanhos transgênicos, assim como experiências recentes na manipulação genética de células doadoras de núcleo e possíveis efeitos da indução gênica à pluripotência na TNCS.