Parkinson's disease (PD) is a disabling and highly costly neurodegenerative condition with worldwide prevalence. Despite advances in treatments that slow progression and minimize locomotor impairments, its clinical management is still a challenge. Previous preclinical studies, using mesenchymal stem cell (MSC) transplantation and isolated physical exercise (EX), reported beneficial results for treatment of PD. Therefore, this experimental randomized study aimed to elucidate the therapeutic potential of combined therapy using adipose-derived human MSCs (ADSCs) grafted into the striatum in conjunction with aerobic treadmill training, specifically in terms of locomotor performance in a unilateral PD rat model induced by 6-hydroxydopamine (6-OHDA). Forty-one male Wistar rats were categorized into five groups in accordance with the type of treatment to which they were subjected (Sham, 6-OHDA − injury, 6-OHDA + exercise, 6-OHDA + cells, and 6-OHDA + combined). Subsequently, dopaminergic depletion was assessed by the methylphenidate challenge and the specified therapeutic intervention was conducted in each group. The foot fault task was performed at the end of the experiment to serve as an assessment of motor skills. The results showed that despite disturbances in motor balance and coordination, locomotor dysfunction was ameliorated in all treatment categories in comparison to the injury group (sign test, p < 0.001, effect size: 0.71). The exercise alone and combined groups were the categories that exhibited the best recovery in terms of movement performance (p < 0.001). Overall, this study confirms that exercise is a powerful option to improve motor function and a promising adjuvant intervention for stem cell transplantation in the treatment of PD motor symptoms.
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.
En la investigación sobre movimiento, la experimentación animal ha proporcionado fundamentación científica para la investigación clínica, mejorando procedimientos diagnósticos y de rehabilitación. Lesiones cerebrales en roedores pueden ser usadas para modelar síntomas locomotores, sensoriales y/o cognitivos. Con el propósito de determinar la funcionalidad locomotriz y sensorial en roedores, se han propuesto varios métodos de evaluación y pronóstico clínico para identificar y evaluar adaptaciones estructurales y mecanismos de neuro-recuperación. Esto ha permitido que métodos de intervención terapéutica, como el ejercicio físico, sean utilizados para restaurar funciones sensitivo-motoras y cognitivas en roedores y humanos. La extrapolación (translación) de los resultados de investigaciones en ciencias básicas a áreas clínicas supone la continua cooperación y retroalimentación entre investigadores y profesionales de la salud, favoreciendo la formulación de intervenciones terapéuticas más eficaces basadas en resultados obtenidos de la experimentación animal. El objetivo de esta revisión es exponer las principales deficiencias motoras y los métodos empleados para determinar la dificultad motriz en la marcha en roedores con lesión cerebrovascular, para lo cual se realizó una revisión de literatura, sobre términos definidos (MeSH), en las bases de datos PsychINFO, Medline y Web of Science, entre enero de 2000 y enero de 2017. Se excluyeron artículos de carácter cualitativo o narrativo, sin revisión por pares, disertaciones, tesis o trabajos de grado y resúmenes de conferencias. Se revisan algunas manifestaciones clínicas, su efecto en la locomotricidad en roedores, algunas metodologías usadas para generar lesiones y para estudiar la función motriz, los principales métodos de medición y algunos aspectos translacionales.
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