This work examines whether microglia-conditioned medium (MCM) is beneficial in stressed spinal cord cells or tissues. MCM was separated into two fractions by 50 kDa molecular cut-off centrifugation. MCM not only promo...This work examines whether microglia-conditioned medium (MCM) is beneficial in stressed spinal cord cells or tissues. MCM was separated into two fractions by 50 kDa molecular cut-off centrifugation. MCM not only promoted survival of neuronal and oligodendroglial cells but effectively reduced LPS stimulation in spinal cord cultures. We further utilized the NYU weight-drop device to induce contusive spinal cord injury (SCI) in rats. Immediately after dropping the impactor from a height of 25 mm onto thoracic spinal segment, MCM was intrathecally administered. At 6 weeks post-injury, SCI rats receiving MCM > 50 kDa treatment showed significant hind-limb improvement over MCM 50 kDa, of microglia was neuroprotective against spinal cord injury.展开更多
Background:Spinocerebellar ataxia type 1(SCA1)is an autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in ATXN1 gene resulting in an expansion of polyglutamine repeats in the ATXN1 pr...Background:Spinocerebellar ataxia type 1(SCA1)is an autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in ATXN1 gene resulting in an expansion of polyglutamine repeats in the ATXN1 protein.Unfortunately,there has yet been any effective treatment so far for SCA1.This study investigated the feasibility of transplanting human umbilical mesenchymal stem cells(HUMSCs)into transgenic SCA1 mice containing an expanded uninterrupted allele with 82 repeats in the ATXN1-coding region.Methods:106 human umbilical mesenchymal stem cells were transplanted into the cerebella at 1 month of age.Results:HUMSCs displayed significant ameliorating effects in SCA1 mice in terms of motor behaviors in balance beam test and open field test as compared with the untransplanted SCA1 mice.HUMSCs transplantation effectively reduced the cerebellar atrophy,salvaged Purkinje cell death,and alleviated molecular layer shrinkage.Electrophysiological studies showed higher amplitudes of compound motor action potentials as indicated by increasing neuronal-muscular response strength to stimuli after stem cell transplantation.At 5 months after transplantation,HUMSCs scattering in the mice cerebella remained viable and secreted cytokines without differentiating into neuronal or glia cells.Conclusions:Our findings provide hope for a new therapeutic direction for the treatment of SCA1.展开更多
文摘This work examines whether microglia-conditioned medium (MCM) is beneficial in stressed spinal cord cells or tissues. MCM was separated into two fractions by 50 kDa molecular cut-off centrifugation. MCM not only promoted survival of neuronal and oligodendroglial cells but effectively reduced LPS stimulation in spinal cord cultures. We further utilized the NYU weight-drop device to induce contusive spinal cord injury (SCI) in rats. Immediately after dropping the impactor from a height of 25 mm onto thoracic spinal segment, MCM was intrathecally administered. At 6 weeks post-injury, SCI rats receiving MCM > 50 kDa treatment showed significant hind-limb improvement over MCM 50 kDa, of microglia was neuroprotective against spinal cord injury.
基金This work was supported by grants from the Ministry of Science and Technology,Taiwan(MOST 103-2314-B-075-032-MY2,MOST 103-2314-B-010-049-MY3,MOST 104-2320-B-010-013,MOST 107-2321-B-010-003 and MOST 107-2314-B-010-017)Taipei Veterans General Hospital(V103C-098 and V104C-035)+1 种基金the Yin Yen-Liang Foundation Development and Construction Plan of the School of Medicine,National Yang-Ming University(107F-M01)the Higher Education Sprout Project by the Ministry of Education(MOE)in Taiwan,as well as the research funds from the Taiwan Ataxia Association and the Hsu Tsung Pei Medical Research Fund.
文摘Background:Spinocerebellar ataxia type 1(SCA1)is an autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in ATXN1 gene resulting in an expansion of polyglutamine repeats in the ATXN1 protein.Unfortunately,there has yet been any effective treatment so far for SCA1.This study investigated the feasibility of transplanting human umbilical mesenchymal stem cells(HUMSCs)into transgenic SCA1 mice containing an expanded uninterrupted allele with 82 repeats in the ATXN1-coding region.Methods:106 human umbilical mesenchymal stem cells were transplanted into the cerebella at 1 month of age.Results:HUMSCs displayed significant ameliorating effects in SCA1 mice in terms of motor behaviors in balance beam test and open field test as compared with the untransplanted SCA1 mice.HUMSCs transplantation effectively reduced the cerebellar atrophy,salvaged Purkinje cell death,and alleviated molecular layer shrinkage.Electrophysiological studies showed higher amplitudes of compound motor action potentials as indicated by increasing neuronal-muscular response strength to stimuli after stem cell transplantation.At 5 months after transplantation,HUMSCs scattering in the mice cerebella remained viable and secreted cytokines without differentiating into neuronal or glia cells.Conclusions:Our findings provide hope for a new therapeutic direction for the treatment of SCA1.
