Excessive noise, ototoxic drugs, infections, autoimmune diseases, and aging can cause loss of spiral ganglion neurons, leading to permanent sensorineural hearing loss in mammals. Stem cells have been confirmed to be a...Excessive noise, ototoxic drugs, infections, autoimmune diseases, and aging can cause loss of spiral ganglion neurons, leading to permanent sensorineural hearing loss in mammals. Stem cells have been confirmed to be able to differentiate into spiral ganglion neurons. Little has been reported on adipose tissue-derived stem cells（ADSCs） for repair of injured spiral ganglion neurons. In this study, we hypothesized that transplantation of neural induced-human ADSCs（NI-h ADSCs） can repair the injured spiral ganglion neurons in guinea pigs with neomycin-induced sensorineural hearing loss. NI-h ADSCs were induced with culture medium containing basic fibroblast growth factor and forskolin and then injected to the injured cochleae. Guinea pigs that received injection of Hanks＇ balanced salt solution into the cochleae were used as controls. Hematoxylin-eosin staining showed that at 8 weeks after cell transplantation, the number of surviving spiral ganglion neurons in the cell transplantation group was significantly increased than that in the control group. Also at 8 weeks after cell transplantation, immunohistochemical staining showed that a greater number of NI-h ADSCs in the spiral ganglions were detected in the cell transplantation group than in the control group, and these NI-h ADSCs expressed neuronal markers neurofilament protein and microtubule-associated protein 2. Within 8 weeks after cell transplantation, the guinea pigs in the cell transplantation group had a gradually decreased auditory brainstem response threshold, while those in the control group had almost no response to 80 d B of clicks or pure tone burst. These findings suggest that a large amount of NI-h ADSCs migrated to the spiral ganglions, survived for a period of time, repaired the injured spiral ganglion cells, and thereby contributed to the recovery of sensorineural hearing loss in guinea pigs.展开更多
Background and early studies： Endogenous tri-potential neural stem cells （NSCs） exist in the adult mammalian central nervous system （CNS）. In the spinal cord, NSCs distribute throughout the entire cord, but exist...Background and early studies： Endogenous tri-potential neural stem cells （NSCs） exist in the adult mammalian central nervous system （CNS）. In the spinal cord, NSCs distribute throughout the entire cord, but exist predominately in white matter tracts. The phenotypic fate of these cells in white matter is glial, largely oligodendrocyte, but not neuronal.展开更多
Objective The microglias is the representative of immune cells in the brain. It plays dual roles of both repairing and damaging in injured nervous system, and works as an inevitable component of the circumstance of in...Objective The microglias is the representative of immune cells in the brain. It plays dual roles of both repairing and damaging in injured nervous system, and works as an inevitable component of the circumstance of injured neurons. This study was aiming at the effects of the microglias on the biological activities of mesenchymal stem cells （MSCs） in the circumstance of injured neurons. Methods MSCs were obtained by primary culture. We adopted PC12 cells （PC12） and BV2 cells （BV2） to substitute for neurons and microglias, respectively. PC12 were injured by aged Aβ1-40 and the supernatant of the injured PC12 was used to set up the circumstance of injured neurons. Transwells were used for co-culture of BV2 and MSCs, which allowed the independent detection of cells after co-culture. Immunofluorescence was used to identify MSCs and neuron-differentiating cells with CD44 and neuron specific enolase （NSE） staining, respectively. MTT assay was adopted to measure the proliferation. Results In the circumstance of both BV2 presence and injured PC 12 supernatant incubation, either the proliferation or the differentiation of MSCs reached the highest, which seemed to be contradictory, but we gave our explanations. With the BV2 co-culture, the proliferation of MSCs tend to be higher, but the neuron-differentiating MSCs were similar to those incubated without BV2 co-culture either in normal or injured in PC12 supernatant. With the incubation of injured PC12 supernatant, the neuron-differentiating cells were significantly higher than that of control （P 〈 0.05）. Conclusion In the circumstance of injured neurons, microlgias tend to promote the MSCs proliferation. Although not helpful in neuron-differentiating, microglias did not exert any negative effect either.展开更多
Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as ...Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as well as embryonic stem cells and induced plu- ripotent stem cells. In particular, transplants of neural progenitor cells （NPCs） have been shown to limit secondary injury and scar formation and create a permissive environment in the injured spinal cord through the provision of neurotrophic molecules and growth supporting matrices that promote growth of injured host axons. Importantly, transplants of NPC are unique in their poten- tial to replace lost neural cells - including neurons, astrocytes,展开更多
Stem cell treatments,and in particular,stem cell transplants have been identified as potential therapeutic strategies for a range of neurodegenerative and acquired conditions of the central nervous system（CNS）.Stem ...Stem cell treatments,and in particular,stem cell transplants have been identified as potential therapeutic strategies for a range of neurodegenerative and acquired conditions of the central nervous system（CNS）.Stem cell transplants are seen as a way of replacing lost neurons,or providing a cellular environment that is more permissible for axon and cell regeneration.展开更多
Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in...Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in a rat model of spinal cord injury and explored potential mechanisms for this effect. Spinal cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra level. One group of injured rats received deferoxamine, a second injured group received saline, and a third group was sham operated. Both 2 days and 2 weeks after spinal cord injury, total iron ion levels and protein expression levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β and the pro-apoptotic protein caspase-3 in the spinal cords of the injured deferoxamine-treated rats were significantly lower than those in the injured saline-treated group. The percentage of the area positive for glial fibrillary acidic protein immunoreactivity and the number of terminal deoxynucleotidyl transferase d UTP nick end labeling-positive cells were also significantly decreased both 2 days and 2 weeks post injury, while the number of Neu N-positive cells and the percentage of the area positive for the oligodendrocyte marker CNPase were increased in the injured deferoxamine-treated rats. At 14–56 days post injury, hind limb motor function in the deferoxamine-treated rats was superior to that in the saline-treated rats. These results suggest that deferoxamine decreases total iron ion, tumor necrosis factor-α, interleukin-1β, and caspase-3 expression levels after spinal cord injury and inhibits apoptosis and glial scar formation to promote motor function recovery.展开更多
Monosialotetrahexosylganglioside（GM1）is a type of glycosphingolipid containing sialic acid that is closely related to cell-cell recognition,adhesion and signal conduction.GM1is mainly composed of ceramide and oligos...Monosialotetrahexosylganglioside（GM1）is a type of glycosphingolipid containing sialic acid that is closely related to cell-cell recognition,adhesion and signal conduction.GM1is mainly composed of ceramide and oligosaccharide chains,and it is the only ganglioside that can permeate the bloodbrain barrier.展开更多
Transcranial magnetic stimulation-a tool used in humans：Transcranial magnetic stimulation（TMS）is a non-invasive widespread clinical tool used to stimulate cortical areas in human subjects.This technique utilizes a ...Transcranial magnetic stimulation-a tool used in humans：Transcranial magnetic stimulation（TMS）is a non-invasive widespread clinical tool used to stimulate cortical areas in human subjects.This technique utilizes a brief,highly intense magnetic field applied to cortical areas,which locally depolarized interneurons（Weber and Eisen,2002）.展开更多
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by Ministry of Education,Science and Technology,No.2010-0025501a grant from Chonnam National University Hospital Biomedical Research Institute,No.CRI11048-1a grant from the Chonnam National University,No.2012-2894
文摘Excessive noise, ototoxic drugs, infections, autoimmune diseases, and aging can cause loss of spiral ganglion neurons, leading to permanent sensorineural hearing loss in mammals. Stem cells have been confirmed to be able to differentiate into spiral ganglion neurons. Little has been reported on adipose tissue-derived stem cells（ADSCs） for repair of injured spiral ganglion neurons. In this study, we hypothesized that transplantation of neural induced-human ADSCs（NI-h ADSCs） can repair the injured spiral ganglion neurons in guinea pigs with neomycin-induced sensorineural hearing loss. NI-h ADSCs were induced with culture medium containing basic fibroblast growth factor and forskolin and then injected to the injured cochleae. Guinea pigs that received injection of Hanks＇ balanced salt solution into the cochleae were used as controls. Hematoxylin-eosin staining showed that at 8 weeks after cell transplantation, the number of surviving spiral ganglion neurons in the cell transplantation group was significantly increased than that in the control group. Also at 8 weeks after cell transplantation, immunohistochemical staining showed that a greater number of NI-h ADSCs in the spiral ganglions were detected in the cell transplantation group than in the control group, and these NI-h ADSCs expressed neuronal markers neurofilament protein and microtubule-associated protein 2. Within 8 weeks after cell transplantation, the guinea pigs in the cell transplantation group had a gradually decreased auditory brainstem response threshold, while those in the control group had almost no response to 80 d B of clicks or pure tone burst. These findings suggest that a large amount of NI-h ADSCs migrated to the spiral ganglions, survived for a period of time, repaired the injured spiral ganglion cells, and thereby contributed to the recovery of sensorineural hearing loss in guinea pigs.
文摘Background and early studies： Endogenous tri-potential neural stem cells （NSCs） exist in the adult mammalian central nervous system （CNS）. In the spinal cord, NSCs distribute throughout the entire cord, but exist predominately in white matter tracts. The phenotypic fate of these cells in white matter is glial, largely oligodendrocyte, but not neuronal.
文摘Objective The microglias is the representative of immune cells in the brain. It plays dual roles of both repairing and damaging in injured nervous system, and works as an inevitable component of the circumstance of injured neurons. This study was aiming at the effects of the microglias on the biological activities of mesenchymal stem cells （MSCs） in the circumstance of injured neurons. Methods MSCs were obtained by primary culture. We adopted PC12 cells （PC12） and BV2 cells （BV2） to substitute for neurons and microglias, respectively. PC12 were injured by aged Aβ1-40 and the supernatant of the injured PC12 was used to set up the circumstance of injured neurons. Transwells were used for co-culture of BV2 and MSCs, which allowed the independent detection of cells after co-culture. Immunofluorescence was used to identify MSCs and neuron-differentiating cells with CD44 and neuron specific enolase （NSE） staining, respectively. MTT assay was adopted to measure the proliferation. Results In the circumstance of both BV2 presence and injured PC 12 supernatant incubation, either the proliferation or the differentiation of MSCs reached the highest, which seemed to be contradictory, but we gave our explanations. With the BV2 co-culture, the proliferation of MSCs tend to be higher, but the neuron-differentiating MSCs were similar to those incubated without BV2 co-culture either in normal or injured in PC12 supernatant. With the incubation of injured PC12 supernatant, the neuron-differentiating cells were significantly higher than that of control （P 〈 0.05）. Conclusion In the circumstance of injured neurons, microlgias tend to promote the MSCs proliferation. Although not helpful in neuron-differentiating, microglias did not exert any negative effect either.
基金NIH PO1 NS055976,Craig H.Neilsen Foundation,and Shriner’s Hospital for Children
文摘Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as well as embryonic stem cells and induced plu- ripotent stem cells. In particular, transplants of neural progenitor cells （NPCs） have been shown to limit secondary injury and scar formation and create a permissive environment in the injured spinal cord through the provision of neurotrophic molecules and growth supporting matrices that promote growth of injured host axons. Importantly, transplants of NPC are unique in their poten- tial to replace lost neural cells - including neurons, astrocytes,
基金supported by University of Technology,Sydney Early Career Research Grant to CAG
文摘Stem cell treatments,and in particular,stem cell transplants have been identified as potential therapeutic strategies for a range of neurodegenerative and acquired conditions of the central nervous system（CNS）.Stem cell transplants are seen as a way of replacing lost neurons,or providing a cellular environment that is more permissible for axon and cell regeneration.
基金supported by the National Natural Science Foundation of China,No.81672171,81330042the International Cooperation Program of National Natural Science Foundation of China,No.81620108018+2 种基金a grant from the Ministry of Science and Technology of China,No.2014DFR31210a grant from the Tianjin Science and Technology Committee of China,No.13RCGFSY19000,14ZCZDSY00044the Youth Foundation of Tianjin Medical University General Hospital of China,No.ZYYFY2015008
文摘Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in a rat model of spinal cord injury and explored potential mechanisms for this effect. Spinal cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra level. One group of injured rats received deferoxamine, a second injured group received saline, and a third group was sham operated. Both 2 days and 2 weeks after spinal cord injury, total iron ion levels and protein expression levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β and the pro-apoptotic protein caspase-3 in the spinal cords of the injured deferoxamine-treated rats were significantly lower than those in the injured saline-treated group. The percentage of the area positive for glial fibrillary acidic protein immunoreactivity and the number of terminal deoxynucleotidyl transferase d UTP nick end labeling-positive cells were also significantly decreased both 2 days and 2 weeks post injury, while the number of Neu N-positive cells and the percentage of the area positive for the oligodendrocyte marker CNPase were increased in the injured deferoxamine-treated rats. At 14–56 days post injury, hind limb motor function in the deferoxamine-treated rats was superior to that in the saline-treated rats. These results suggest that deferoxamine decreases total iron ion, tumor necrosis factor-α, interleukin-1β, and caspase-3 expression levels after spinal cord injury and inhibits apoptosis and glial scar formation to promote motor function recovery.
基金supported by the National Natural Science Foundation of China(General Program),No.81373095
文摘Monosialotetrahexosylganglioside（GM1）is a type of glycosphingolipid containing sialic acid that is closely related to cell-cell recognition,adhesion and signal conduction.GM1is mainly composed of ceramide and oligosaccharide chains,and it is the only ganglioside that can permeate the bloodbrain barrier.
文摘Transcranial magnetic stimulation-a tool used in humans：Transcranial magnetic stimulation（TMS）is a non-invasive widespread clinical tool used to stimulate cortical areas in human subjects.This technique utilizes a brief,highly intense magnetic field applied to cortical areas,which locally depolarized interneurons（Weber and Eisen,2002）.
