RESUMEN
Spinal cord injury (SCI) remains an important public health problem which often causes permanent loss of muscle strength, sensation, and function below the site of the injury, generating physical, psychological, and social impacts throughout the lives of the affected individuals, since there are no effective treatments available. The use of stem cells has been investigated as a therapeutic approach for the treatment of SCI. Although a significant number of studies have been conducted in pre-clinical and clinical settings, so far there is no established cell therapy for the treatment of SCI. One aspect that makes it difficult to evaluate the efficacy is the heterogeneity of experimental designs in the clinical trials that have been published. Cell transplantation methods vary widely among the trials, and there are still no standardized protocols or recommendations for the therapeutic use of stem cells in SCI. Among the different cell types, mesenchymal stem/stromal cells (MSCs) are the most frequently tested in clinical trials for SCI treatment. This study reviews the clinical applications of MSCs for SCI, focusing on the critical analysis of 17 clinical trials published thus far, with emphasis on their design and quality. Moreover, it highlights the need for more evidence-based studies designed as randomized controlled trials and potential challenges to be addressed in context of stem cell therapies for SCI.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Traumatismos de la Médula Espinal , Humanos , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Resultado del TratamientoRESUMEN
ABSTRACT Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease and has a high frequency among dermatological diseases. The interaction of genetic factors, skin and environmental conditions affect the expression of the disease, developing a complex pathology. Current multimodal treatment has numerous adverse effects and variations in its efficacy and safety, demonstrating the need to develop safe and effective therapeutic resources for patients with CAD. Mesenchymal stem cells (MSCs) are multipotent cells, with special characteristics, such as self-renewal, immunomodulatory properties, and de-differentiation, making them useful for several clinical problems. The discovery of the immunosuppressive effect of MSCs on T cells has opened the potential for new perspectives with its use as a therapeutic agent for immune diseases, such as CAD. The scarce number of research using the MSC as a treatment for CAD result in the lack of knowledge about the benefits and possible protocols to be followed for the use of this cell therapy. In this review, we highlighted the clinical studies and potential biological mechanisms of MSC-based cell therapy effects attenuating canine atopic dermatitis compared to conventional treatment, which might lead to a safe improvement of the animals clinical condition in a short period without causing adverse effects.
RESUMO A dermatite atópica canina (DAC) é uma doença inflamatória crônica da pele e tem alta frequência entre as doenças dermatológicas. A interação de fatores genéticos, pele e condições ambientais afetam a expressão da doença, desenvolvendo uma patologia complexa. O tratamento multimodal atual apresenta inúmeros efeitos adversos e variações em sua eficácia e segurança, demonstrando a necessidade de desenvolver recursos terapêuticos seguros e eficazes para pacientes com DAC. As células-tronco mesenquimais (CTM) são células multipotentes, com características especiais, como auto renovação, propriedades imunomoduladoras e desdiferenciação, tornando-se úteis para diversos problemas clínicos. A descoberta do efeito imunossupressor das CTMs sobre as células T abriu o potencial para novas perspectivas com sua utilização como agente terapêutico para doenças imunológicas, como a DAC. O escasso número de pesquisas utilizando o MSC como tratamento para DAC resulta no desconhecimento dos benefícios e dos possíveis protocolos a serem seguidos para a utilização dessa terapia celular. Nesta revisão, destacamos os estudos clínicos e os potenciais mecanismos biológicos dos efeitos da terapia celular baseada em MSC que atenuam a dermatite atópica canina em comparação com o tratamento convencional, podendo levar a uma melhora segura da condição clínica do animal em um curto período, sem causar efeitos adversos.
RESUMEN
Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease and has a high frequency among dermatological diseases. The interaction of genetic factors, skin and environmental conditions affect the expression of the disease, developing a complex pathology. Current multimodal treatment has numerous adverse effects and variations in its efficacy and safety, demonstrating the need to develop safe and effective therapeutic resources for patients with CAD. Mesenchymal stem cells (MSCs) are multipotent cells, with special characteristics, such as self-renewal, immunomodulatory properties, and de-differentiation, making them useful for several clinical problems. The discovery of the immunosuppressive effect of MSCs on T cells has opened the potential for new perspectives with its use as a therapeutic agent for immune diseases, such as CAD. The scarce number of research using the MSC as a treatment for CAD result in the lack of knowledge about the benefits and possible protocols to be followed for the use of this cell therapy. In this review, we highlighted the clinical studies and potential biological mechanisms of MSC-based cell therapy effects attenuating canine atopic dermatitis compared to conventional treatment, which might lead to a safe improvement of the animals clinical condition in a short period without causing adverse effects.(AU)
A dermatite atópica canina (DAC) é uma doença inflamatória crônica da pele e tem alta frequência entre as doenças dermatológicas. A interação de fatores genéticos, pele e condições ambientais afetam a expressão da doença, desenvolvendo uma patologia complexa. O tratamento multimodal atual apresenta inúmeros efeitos adversos e variações em sua eficácia e segurança, demonstrando a necessidade de desenvolver recursos terapêuticos seguros e eficazes para pacientes com DAC. As células-tronco mesenquimais (CTM) são células multipotentes, com características especiais, como auto renovação, propriedades imunomoduladoras e desdiferenciação, tornando-se úteis para diversos problemas clínicos. A descoberta do efeito imunossupressor das CTMs sobre as células T abriu o potencial para novas perspectivas com sua utilização como agente terapêutico para doenças imunológicas, como a DAC. O escasso número de pesquisas utilizando o MSC como tratamento para DAC resulta no desconhecimento dos benefícios e dos possíveis protocolos a serem seguidos para a utilização dessa terapia celular. Nesta revisão, destacamos os estudos clínicos e os potenciais mecanismos biológicos dos efeitos da terapia celular baseada em MSC que atenuam a dermatite atópica canina em comparação com o tratamento convencional, podendo levar a uma melhora segura da condição clínica do animal em um curto período, sem causar efeitos adversos.(AU)
Asunto(s)
Animales , Perros , Perros , Células Madre Mesenquimatosas/clasificación , Dermatitis , Enfermedades de la Piel/veterinariaRESUMEN
Human-induced pluripotent stem cell (hiPSC) CBTCi001-A line was generated from a healthy 30-year old male dermal fibroblasts using non-integrative reprogramming method using episomal-based plasmids expressing OCT4, SOX2, KLF4, and MYCL. Characterization of CBTCi001-A was confirmed by the expression of typical markers of pluripotency and differentiation potential in vitro.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Línea Celular/citología , Dermis/citología , Fibroblastos/citología , Células Madre Pluripotentes Inducidas/citología , Donantes de Tejidos , Adulto , Diferenciación Celular , Humanos , Factor 4 Similar a Kruppel , Masculino , Reproducibilidad de los ResultadosRESUMEN
Sickle cell disease (SCD) is one of the most prevalent and severe monogenetic disorders. Previously, we generated iPS cell lines from SCD patients. Here, we generated iPS cell lines from three age-, ethnicity- and gender-matched healthy individuals as control cell lines. Cell reprogramming was performed using erythroblasts expanded from PBMC by a non-integrative method. SCD-iPSC controls expressed pluripotency markers, presented a normal karyotype, were able to differentiate into the three germ layers in embryoid body spontaneous differentiation and confirmed to be integration-free. The cell lines generated here may be used as matched healthy controls for SCD studies.
Asunto(s)
Anemia de Células Falciformes , Técnicas de Reprogramación Celular , Eritroblastos , Células Madre Pluripotentes Inducidas/metabolismo , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/metabolismo , Anemia de Células Falciformes/patología , Técnicas de Cultivo de Célula , Línea Celular , Eritroblastos/metabolismo , Eritroblastos/patología , Humanos , Células Madre Pluripotentes Inducidas/patologíaRESUMEN
Chronic Chagas disease cardiomyopathy, caused by Trypanosoma cruzi infection, is a major cause of heart failure in Latin America. Galectin-3 (Gal-3) has been linked to cardiac remodeling and poor prognosis in heart failure of different etiologies. Herein, we investigated the involvement of Gal-3 in the disease pathogenesis and its role as a target for disease intervention. Gal-3 expression in mouse hearts was evaluated during T. cruzi infection by confocal microscopy and flow cytometry analysis, showing a high expression in macrophages, T cells, and fibroblasts. In vitro studies using Gal-3 knockdown in cardiac fibroblasts demonstrated that Gal-3 regulates cell survival, proliferation, and type I collagen synthesis. In vivo blockade of Gal-3 with N-acetyl-d-lactosamine in T. cruzi-infected mice led to a significant reduction of cardiac fibrosis and inflammation in the heart. Moreover, a modulation in the expression of proinflammatory genes in the heart was observed. Finally, histological analysis in human heart samples obtained from subjects with Chagas disease who underwent heart transplantation showed the expression of Gal-3 in areas of inflammation, similar to the mouse model. Our results indicate that Gal-3 plays a role in the pathogenesis of experimental chronic Chagas disease, favoring inflammation and fibrogenesis. Moreover, by demonstrating Gal-3 expression in human hearts, our finding reinforces that this protein could be a novel target for drug development for Chagas cardiomyopathy.