RESUMO
Multiple Sclerosis (MS) is a neurodegenerative, demyelinating, and chronic inflammatory disease characterized by Central Nervous System (CNS) lesions that lead to high levels of disability and severe physical and cognitive disturbances. Conventional therapies are not enough to control the neuroinflammatory process in MS and are not able to inhibit ongoing damage to the CNS. Thus, the secretome of mesenchymal stem cells (MSC-S) has been postulated as a potential therapy that could mitigate symptoms and disease progression. We considered that its combination with physical exercise (EX) could induce superior effects and increase the MSC-S effectiveness in this condition. Recent studies have revealed that both EX and MSC-S share similar mechanisms of action that mitigate auto-reactive T cell infiltration, regulate the local inflammatory response, modulate the proinflammatory profile of glial cells, and reduce neuronal damage. Clinical and experimental studies have reported that these treatments in an isolated way also improve myelination, regeneration, promote the release of neurotrophic factors, and increase the recruitment of endogenous stem cells. Together, these effects reduce disease progression and improve patient functionality. Despite these results, the combination of these methods has not yet been studied in MS. In this review, we focus on molecular elements and cellular responses induced by these treatments in a separate way, showing their beneficial effects in the control of symptoms and disease progression in MS, as well as indicating their contribution in clinical fields. In addition, we propose the combined use of EX and MSC-S as a strategy to boost their reparative and immunomodulatory effects in this condition, combining their benefits on synaptogenesis, neurogenesis, remyelination, and neuroinflammatory response. The findings here reported are based on the scientific evidence and our professional experience that will bring significant progress to regenerative medicine to deal with this condition.
Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Esclerose Múltipla , Progressão da Doença , Exercício Físico , Humanos , Inflamação/patologia , Inflamação/terapia , Esclerose Múltipla/terapia , SecretomaRESUMO
Molecules of animal or bacterial origin, which pose a risk for zoonoses or immune rejection, are commonly used for extraction, culture, and cryopreservation of mesenchymal stem cells. There is no sequential and orderly protocol for producing human adipose-derived stem cells (hASCs) under xeno-free conditions. After standardizing a human platelet lysate (hPL) production protocol, four human adipose tissue samples were processed through explants with fetal bovine serum (FBS)-supplemented or hPL-supplemented media for extracting the adipose-derived stem cells. The cells were cultivated in cell culture medium + hPL (5%) or FBS (10%). The cellular replication rate, immunophenotype, and differentiation potential were evaluated at fourth passage. Cellular viability was evaluated before and after cryopreservation of the cells, with an hPL-based solution compared with an FBS-based solution. The explants cultured in hPL-supplemented media showed earlier and faster hASC proliferation than did those supplemented with FBS. Likewise, cells grown in hPL-supplemented media showed a greater proliferation rate, without losing the immunophenotype. Osteogenic differentiation of xeno-free hASC was higher than the hASC produced in standard conditions. However, adipogenic differentiation was reduced in xeno-free hASC. Finally, the cells cryopreserved in an hPL-based solution showed a higher cellular viability than the cells cryopreserved in an FBS-based. In conclusion, we have developed a complete xeno-free protocol for extracting, culturing, and cryopreserving hASCs that can be safely implemented in clinical studies.
Assuntos
Adipócitos/citologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular/efeitos dos fármacos , Meios de Cultura/farmacologia , Células-Tronco Mesenquimais/citologia , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Animais , Plaquetas/citologia , Bovinos , Proliferação de Células/efeitos dos fármacos , Criopreservação , Humanos , Osteogênese/efeitos dos fármacosRESUMO
Mesenchymal stem cell (MSC) transplantation has proved to be a promising strategy in cell therapy and regenerative medicine. Although their mechanism of action is not completely clear, it has been suggested that their therapeutic activity may be mediated by a paracrine effect. The main goal of this study was to evaluate by radiographic, morphometric and histological analysis the ability of mesenchymal stem cells derived from human adipose tissue (Ad-MSC) and their conditioned medium (CM), to repair surgical bone lesions using an in vivo model (rabbit mandibles). The results demonstrated that both, Ad-MSC and CM, induce bone regeneration in surgically created lesions in rabbit's jaws, suggesting that Ad-MSC improve the process of bone regeneration mainly by releasing paracrine factors. The evidence of the paracrine effect of MSC on bone regeneration has a major impact on regenerative medicine, and the use of their CM can address some issues and difficulties related to cell transplants. In particular, CM can be easily stored and transported, and is easier to handle by medical personnel during clinical procedures.
Assuntos
Tecido Adiposo/citologia , Regeneração Óssea/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Arcada Osseodentária/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Comunicação Parácrina , Medicina Regenerativa , Tecido Adiposo/efeitos dos fármacos , Adulto , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Hidrogéis , Técnicas Imunoenzimáticas , Arcada Osseodentária/efeitos dos fármacos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Procedimentos Cirúrgicos Ortognáticos , Coelhos , Cicatrização , Adulto JovemRESUMO
INTRODUCTION: The use of mesenchymal stem cells in clinical practice has increased considerably in the last decade because they play a supporting role in the processes of tissue repair and regeneration, becoming the main tool of cell therapy for the treatment of diseases functionally affecting bone and cartilage tissue . OBJECTIVE: To evaluate in vitro the proliferative and osteogenic differentiation ability of mesenchymal stem cells derived from human adipose tissue in a blood plasma hydrogel. MATERIALS AND METHODS: Mesenchymal stem cells were obtained from human adipose tissue explants and characterized by flow cytometry. Their multipotentiality was demonstrated by their ability to differentiate to adipogenic and osteogenic lineages. Cell proliferation and osteogenic differentiation ability of the cells cultured in blood plasma hydrogels were also evaluated. RESULTS: Mesenchymal stem cells derived from human adipose tissue growing in human blood plasma hydrogels showed a pattern of proliferation similar to that of the cells cultured in monolayer and also maintained their ability to differentiate to osteogenic lineage. CONCLUSIONS: Human blood plasma hydrogels are a suitable support for proliferation and osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue and provides a substrate that is autologous, biocompatible, reabsorbable, easy to use, potentially injectable and economic, which could be used as a successful strategy for the management and clinical application of cell therapy in regenerative medicine.
Assuntos
Diferenciação Celular , Proliferação de Células , Células-Tronco Mesenquimais/fisiologia , Osteogênese , Tecido Adiposo/citologia , Sangue , Células Cultivadas , Meios de Cultura , Humanos , HidrogéisRESUMO
Introducción. La utilización de las células madre mesenquimales en la práctica clínica ha aumentado considerablemente en la última década, ya que juegan un papel favorable en los procesos de reparación y regeneración tisular, siendo la principal herramienta de la terapia celular para el tratamiento de enfermedades que afectan funcionalmente el tejido óseo y cartilaginoso. Objetivo. Evaluar la proliferación y capacidad de diferenciación osteogénica in vitro de células madre mesenquimales derivadas de tejido adiposo humano en un hidrogel de plasma sanguíneo. Materiales y métodos. Se obtuvieron células madre mesenquimales a partir de explantes de tejido adiposo humano y se caracterizaron por citometría de flujo; se buscó demostrar su multipotencialidad por su capacidad de diferenciación osteogénica y adipogénica. Se evaluó la proliferación celular y la capacidad de diferenciación osteogénica de las células cultivadas en hidrogeles de plasma sanguíneo. Resultados. Las células madre mesenquimales derivadas de tejido adiposo cultivadas en el hidrogel de plasma sanguíneo humano mostraron un patrón de proliferación muy similar al de las células cultivadas en monocapa y, además, mantuvieron su capacidad de diferenciación hacia el linaje osteogénico. Conclusiones. El hidrogel de plasma sanguíneo humano es un soporte adecuado para que las células madre mesenquimales derivadas de tejido adiposo humano proliferen y se diferencien hacia el linaje osteogénico y constituye un vehículo adecuado para su administración en regeneración del tejido óseo.
Introduction: The use of mesenchymal stem cells in clinical practice has increased considerably in the last decade because they play a supporting role in the processes of tissue repair and regeneration, becoming the main tool of cell therapy for the treatment of diseases functionally affecting bone and cartilage tissue . Objective: To evaluate in vitro the proliferative and osteogenic differentiation ability of mesenchymal stem cells derived from human adipose tissue in a blood plasma hydrogel. Materials and methods: Mesenchymal stem cells were obtained from human adipose tissue explants and characterized by flow cytometry. Their multipotentiality was demonstrated by their ability to differentiate to adipogenic and osteogenic lineages. Cell proliferation and osteogenic differentiation ability of the cells cultured in blood plasma hydrogels were also evaluated. Results: Mesenchymal stem cells derived from human adipose tissue growing in human blood plasma hydrogels showed a pattern of proliferation similar to that of the cells cultured in monolayer and also maintained their ability to differentiate to osteogenic lineage. Conclusions: Human blood plasma hydrogels are a suitable support for proliferation and osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue and provides a substrate that is autologous, biocompatible, reabsorbable, easy to use, potentially injectable and economic, which could be used as a successful strategy for the management and clinical application of cell therapy in regenerative medicine.
Assuntos
Humanos , Diferenciação Celular , Proliferação de Células , Células-Tronco Mesenquimais/fisiologia , Osteogênese , Tecido Adiposo/citologia , Sangue , Células Cultivadas , Meios de Cultura , HidrogéisRESUMO
INTRODUCTION: Spinal cord injury is a catastrophic event with permanent consequences during the all life. Treatment research has been based in the development of therapies that reduce the discapacity, but since the nineties there has been an important advance and several cellular transplants have been tested in spinal cord animal models, like Schwann cells, astrocytes and olfactory and olfactory ensheathing cells (OEC). AIM: Detailed account of spinal cord injury pathogeny, primary and secondary, and the OEC mechanisms for the regeneration effects that have been described in the literature. DEVELOPMENT: After the trauma, spinal cord injury develops in two phases, the primary injury with characteristics compression lesions, and the secondary produce for several factors that occur in parallel and include: vascular, cellular and molecular factors, and glial scar formation. The most of spinal cord models and OEC transplants have been reported functional recovery, remielinization and axonal regeneration. These cells exert their action in a direct way by producing grow factors and in an indirect way inducing directly neuronal an axonal regeneration and remielinization. CONCLUSIONS: OEC are a therapeutic option in patients with spinal cord injury, because they induce in a direct or indirect way, neuronal and axonal regeneration, remielinization, decrease the glial scar and produce other effects that conduce a functional recovery.
TITLE: Patogenia de la lesion medular y mecanismos de reparacion inducidos por las celulas de la glia envolvente olfatoria.Introduccion. La lesion medular es un evento catastrofico, cuyas consecuencias persisten durante toda la vida del paciente. La investigacion en tratamiento se ha basado principalmente en el desarrollo de terapias que reduzcan la discapacidad, pero desde los anos noventa hay un avance significativo y se han probado varios trasplantes celulares en modelos animales de lesion medular, celulas de Schwann, astrocitos y celulas de la glia envolvente olfatoria (CGEO). Objetivo. Hacer un recuento detallado de la patogenia de la lesion medular primaria y secundaria y de los mecanismos por los cuales las CGEO inducirian sus posibles efectos regenerativos descritos en la bibliografia. Desarrollo. Despues del traumatismo, la lesion se desarrolla en dos fases, la primaria se caracteriza por las lesiones de compresion y la secundaria se produce por una serie de factores que se dan en paralelo y que incluyen factores vasculares, celulares, moleculares y formacion de cicatriz glial. La mayoria de los modelos de lesion medular y trasplante con CGEO han comunicado recuperacion funcional, remielinizacion y regeneracion axonal. Estas celulas ejercen su accion de manera indirecta a traves de la produccion de factores de crecimiento y de manera directa induciendo regeneracion neuronal, axonal y remielinizacion. Conclusiones. Las CGEO son una opcion terapeutica en pacientes con lesion medular debido a que inducen de modo directo o indirecto regeneracion neuronal, axonal, remielinizacion de axones, disminucion de cicatriz glial y otros efectos que conducen a la recuperacion funcional.
Assuntos
Transplante de Células , Bulbo Olfatório/citologia , Regeneração/fisiologia , Traumatismos da Medula Espinal/etiologia , Cicatrização/fisiologia , Animais , Astrócitos/fisiologia , Cicatriz/patologia , Citocinas/fisiologia , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/fisiopatologia , Edema/etiologia , Humanos , Isquemia/etiologia , Linfócitos/fisiologia , Macrófagos/fisiologia , Camundongos , Microcirculação , Microglia/fisiologia , Fatores de Crescimento Neural/fisiologia , Fatores de Crescimento Neural/uso terapêutico , Proteínas do Tecido Nervoso/fisiologia , Neurogênese , Neutrófilos/fisiologia , Ratos , Degeneração Retrógrada/fisiopatologia , Medula Espinal/irrigação sanguínea , Compressão da Medula Espinal/complicações , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/cirurgia , Células-Tronco/fisiologiaRESUMO
La reprogramación de células somáticas para generar células madre pluripotentes inducidas (iPS), ha sido uno de los avances más importantes de la biología en los últimos años. La identificación de un grupo de factores de transcripción y más recientemente de algunos compuestos químicos que pueden inducir la pluripotencia en células somáticas, brinda una oportunidad única para el estudio de los mecanismos celulares y moleculares de la diferenciación celular y promete la posibilidad de generar células pluripotentes paciente-específicas para el tratamiento de múltiples enfermedades en protocolos terapia celular y medicina regenerativa...
Reprogramming of somatic cells to generate induced pluripotent stem cells (iPS), has been one of the most important advances in biology in recent years. The identification of a group of transcription factors and more recently of some chemical compounds that can induce pluripotency in somatic cells provides a unique opportunity to study cellular and molecular mechanisms of cell differentiation and promises the possibility of generating patient-specific pluripotent stem cells for the treatment of multiple diseases in protocols of cell therapy and regenerative medicine...
A reprogramação de células somáticas para gerar células-tronco pluripotentes induzidas (iPS), tem sido um dos mais importantes avanços na biologia nos últimos anos. A identificação de um conjunto de fatores de transcrição e, mais recentemente, de alguns compostos químicos que podem induzir pluripotência em células somáticas produzem uma oportunidade única para estudar os mecanismos celulares e moleculares da diferenciação celular e promete a capacidade de gerar células pluripotentes doente-específicas para o tratamento de doenças múltiplas nos protocolos de terapía celular e medicina regenerativa...
Assuntos
Humanos , Reprogramação Celular , Células-TroncoRESUMO
Las células madre se caracterizan por su capacidad de autorenovación y de diferenciación a varios linajes celulares. Existe un buen numero de evidencias expermentales que apoyan la idea de que las células madre adultas poseen la capacidad de generar tipos celulares especializados, diferentes al de su origen embrionario, cuestionando de esta manera el paradigma tradicional de la biología del desarrollo y sugiriendo que estas células poseen una enorme plasticidad. Los datos sugieren que las células madre adultas tienen la capacidad de transdiferenciarse y aunque se han postulado mecanismos alternativos como la fusión celular, aparentemente esta transdiferenciación puede ocurrir a través de un proceso de de-diferenciación y re-diferenciación. Es de esperar que en los proximos años se avance en el entendimiento del fenómeno de la plasticidad de las células madre adultas y en el entendimiento de los mecanismos moleculares y factores que la regulan y que este conocimiento redunde en el diseño de nuevas estrategias aplicadas a los campos de regeneración tisular y la terapia celular