RESUMEN
Age-related macular degeneration (AMD) is the leading cause of adult blindness in developed countries and is characterized by progressive degeneration of the macula, the central region of the retina. A human induced pluripotent stem cell (hiPSC) line was derived from peripheral blood mononuclear cells (PBMCs) from a patient with a clinical diagnosis of dry AMD carrying the CFH Y402H polymorphism. Sendai virus was using for reprogramming and the pluripotent and differentiation capacity of the cells were assessed by immunocytochemistry and RT-PCR.
Asunto(s)
Técnicas de Reprogramación Celular , Células Madre Pluripotentes Inducidas , Degeneración Macular , Polimorfismo Genético , Anciano de 80 o más Años , Línea Celular , Factor H de Complemento/genética , Factor H de Complemento/metabolismo , Femenino , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Degeneración Macular/genética , Degeneración Macular/metabolismo , Degeneración Macular/patologíaRESUMEN
Stem cells (SCs) represent a new therapeutic approach for spinal cord injury (SCI) by enabling improved sensory and motor functions in animal models. The main goal of SC-based therapy for SCI is the replacement of neurons and glial cells that undergo cell death soon after injury. Stem cells are able to promote remyelination via oligodendroglia cell replacement to produce trophic factors enhancing neurite outgrowth, axonal elongation, and fiber density and to activate resident or transplanted progenitor cells across the lesion cavity. While several SC transplantation strategies have shown promising yet partial efficacy, mechanistic proof is generally lacking and is arguably the largest impediment toward faster progress and clinical application. The main challenge ahead is to spur on cooperation between clinicians, researchers, and patients in order to define and optimize the mechanisms of SC function and to establish the ideal source/s of SCs that produce efficient and also safe therapeutic approaches.
Asunto(s)
Traumatismos de la Médula Espinal/terapia , Trasplante de Células Madre , Células Madre/citología , Animales , Humanos , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/fisiopatologíaRESUMEN
Spinal cord injury (SCI) results in neural loss and consequently motor and sensory impairment below the injury. There are currently no effective therapies for the treatment of traumatic SCI in humans. Different kinds of cells including embryonic, fetal, and adult stem cells have been transplanted into animal models of SCI resulting in sensorimotor benefits. Transplantation of human embryonic stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neural cells is nowadays a promising therapy for SCI. This review updates the recent progress in preclinical studies and discusses the advantages and flaws of various neural cell types derived from hESCs and hiPSCs. Before introducing the stem cell replacement strategies in clinical practice, this complex field needs to advance significantly in understanding the lesion itself, the animal model adequacy, and improve cell replacement source. This knowledge will contribute to the successful translation from animals to humans and lead to established guidelines for rigorous safety screening in order to be implemented in clinical practice.
Asunto(s)
Células Madre Embrionarias/trasplante , Células Madre Pluripotentes/trasplante , Traumatismos de la Médula Espinal/cirugía , Animales , Células Madre Embrionarias/metabolismo , Células Madre Embrionarias/patología , Humanos , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/patología , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patologíaRESUMEN
Human embryonic stem cells (hESC) hold great promise for the treatment of patients with many neurodegenerative diseases particularly those arising from cell loss or neural dysfunction including spinal cord injury. This study evaluates the therapeutic effects of transplanted hESC-derived oligodendrocyte progenitors (OPC) and/or motoneuron progenitors (MP) on axonal remyelination and functional recovery of adult rats after complete spinal cord transection. OPC and/or MP were grafted into the site of injury in the acute phase. Based on Basso-Beattie-Bresnahan scores recovery of locomotor function was significantly enhanced in rats treated with OPC and/or MP when compared with control animals. When transplanted into the spinal cord immediately after complete transection, OPC and MP survived, migrated, and differentiated into mature oligodendrocytes and neurons showing in vivo electrophysiological activity. Taken together, these results indicate that OPC and MP derived from hESC could be a useful therapeutic strategy to repair injured spinal cord.
Asunto(s)
Células Madre Embrionarias/trasplante , Actividad Motora , Neuronas Motoras/trasplante , Regeneración Nerviosa , Oligodendroglía/trasplante , Traumatismos de la Médula Espinal/cirugía , Animales , Diferenciación Celular , Movimiento Celular , Supervivencia Celular , Células Cultivadas , Modelos Animales de Enfermedad , Células Madre Embrionarias/metabolismo , Potenciales Evocados Motores , Regulación de la Expresión Génica , Proteínas Fluorescentes Verdes/biosíntesis , Proteínas Fluorescentes Verdes/genética , Humanos , Neuronas Motoras/metabolismo , Regeneración Nerviosa/genética , Oligodendroglía/metabolismo , Ratas , Recuperación de la Función , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Traumatismos de la Médula Espinal/fisiopatología , Factores de Tiempo , TransfecciónRESUMEN
The cerebellum has critical roles in motor and sensory learning and motor coordination. Many cerebellum-related disorders indicate cell therapy as a possible treatment of neural loss. Here we show that application of inductive signals involved in early patterning of the cerebellar region followed by application of different factors directs human embryonic stem cell differentiation into cerebellar-like cells such as granule neurons, Purkinje cells, interneuron, and glial cells. Neurons derived using our protocol showed a T-shaped polarity phenotype and express similar markers to the developed human cerebellum. Electrophysiological measurements confirmed functional electrical properties compatible with these cells. In vivo implantation of differentiated human embryonic stem cells transfected with MATH1-GFP construct into neonatal mice resulted in cell migration across the molecular and the Purkinje cell layers and settlement in the internal molecular layers. Our findings demonstrate that the universal mechanisms involved in the development of cerebellum can be efficiently recapitulated in vitro, which enables the design of new strategies for cell replacement therapy, to study early human development and pathogenesis of neurodegenerative diseases.