RESUMEN
BACKGROUND: Although administration of various stem cells has shown promise in stroke models, neural stem cells (NSCs) derived from human induced pluripotent stem cells (iPSCs) have advantages over other cell types. We studied whether these cells could survive, differentiate, and improve stroke recovery in an ischemic stroke model. METHODS: Human iPSCs were induced in vitro to an early NSC stage. One week after focal cerebral ischemia, 20 rats received cells or vehicle by intracerebral injection. Graft cell fate, infarct volume, and behavioral deficits were assessed. RESULTS: Graft cells were found in 8 of the transplanted rats (80%), with estimated mean graft cell numbers nearly double the amount transplanted 1 month later. Graft cells also expressed markers of NSCs in 5 rats (63%), neurons in all 8 rats (100%), rare astrocytes in 4 rats (50%), and signs of proliferation in 4 rats (50%), but no tumor formation was observed. Stroke volume and behavioral recovery were similar between the groups. CONCLUSIONS: To our knowledge, this is the first report of transplantation of NSCs derived from human iPSCs in a stroke model. Human iPSC-derived NSCs survived in the postischemic rat brain and appeared to differentiate, primarily into neurons. This cell transplantation approach for stroke appears to be feasible, but further optimization is needed.
Asunto(s)
Encéfalo/cirugía , Diferenciación Celular , Células Madre Pluripotentes Inducidas/trasplante , Infarto de la Arteria Cerebral Media/cirugía , Regeneración Nerviosa , Células-Madre Neurales/trasplante , Animales , Conducta Animal , Encéfalo/patología , Encéfalo/fisiopatología , Línea Celular , Proliferación Celular , Supervivencia Celular , Modelos Animales de Enfermedad , Humanos , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/fisiopatología , Masculino , Actividad Motora , Ratas , Ratas Wistar , Recuperación de la Función , Factores de TiempoRESUMEN
Behçet disease (BD) is a chronic relapsing autoimmune disease. Involvement of the nervous system occurs in 5-50% and is referred to as Neuro-Behçet's (NBD). The clinical diagnosis of NBD can be challenging, particularly when the history is atypical and the systemic manifestations of the disorder are absent or scant. We report a young Caucasian man who presented with a non-specific systemic illness evolving rapidly to a basilar meningitis with a neutrophilic pleocytosis. Shortly afterwards, he developed a cervical myelopathy and ultimately a longitudinally extensive transverse myelitis and brainstem involvement with an active uveitis. There was no history of recurrent oral aphthous ulcers or genital ulcers, other skin lesions, or thrombophlebitis. The diagnosis was supported by the clinical, radiographic and laboratory findings including heterozygosity for the HLA-B51 allele on genetic testing. NBD must be included in the differential diagnosis of longitudinally extensive transverse myelitis, especially when it is associated with uveitis.