Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a p...Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.展开更多
Extracellular matrix(ECM)influences cell differentiation through its structural and biochemical properties.In nervous system,neuronal behavior is influenced by these ECMs structures which are present in a meshwork,fib...Extracellular matrix(ECM)influences cell differentiation through its structural and biochemical properties.In nervous system,neuronal behavior is influenced by these ECMs structures which are present in a meshwork,fibrous,or tubular forms encompassing specific molecular compositions.In addition to contact guidance,ECM composition and structures also exert its effect on neuronal differentiation.This short report reviewed the native ECM structure and composition in central nervous system and peripheral nervous system,and their impact on neural regeneration and neuronal differentiation.Using topographies,stem cells have been differentiated to neurons.Further,focussing on engineered biomimicking topographies,we highlighted the role of anisotropic topographies in stem cell differentiation to neurons and its recent temporal application for efficient neuronal differentiation.展开更多
Focal ischemic stroke（FIS）results from the lack of blood flow in a particular region of the brain and accounts for about 80%of all human strokes.Although tremendous efforts have been made in translational research,t...Focal ischemic stroke（FIS）results from the lack of blood flow in a particular region of the brain and accounts for about 80%of all human strokes.Although tremendous efforts have been made in translational research,the treatment strategies are still limited.Tissue plasminogen activator is the only FDA-approved drug currently available for acute stroke treatment,展开更多
There are more than a thousand trillion specific synaptic connections in the human brain and over a million new specific connections are formed every second during the early years of life. The assembly of these stagge...There are more than a thousand trillion specific synaptic connections in the human brain and over a million new specific connections are formed every second during the early years of life. The assembly of these staggeringly complex neuronal circuits requires specific cell-surface molecular tags to endow each neuron with a unique identity code to discriminate self from non-self. The clustered protocadherin(Pcdh) genes, which encode a tremendous diversity of cell-surface assemblies, are candidates for neuronal identity tags. We describe the adaptive evolution,genomic structure, and regulation of expression of the clustered Pcdhs. We specifically focus on the emerging3-D architectural and biophysical mechanisms that generate an enormous number of diverse cell-surface Pcdhs as neural codes in the brain.展开更多
Enolase is a multifunctional enzyme primarily involved in catalyzing the conversion of 2-phosphoglycerate to phosphoenolpyruvate during glycolysis and the reverse reaction during gluconeogenesis[1-4].Though typically ...Enolase is a multifunctional enzyme primarily involved in catalyzing the conversion of 2-phosphoglycerate to phosphoenolpyruvate during glycolysis and the reverse reaction during gluconeogenesis[1-4].Though typically expressed in the cytosol,enolase has been shown to migrate to the cell surface upon inflammatory signal[3].展开更多
Ischemic stroke is a devastating disease that affects millions of patients worldwide.Unfortunately,there are no effective medications for mitigating brain injury after ischemic stroke.TRP channels are evolutionally an...Ischemic stroke is a devastating disease that affects millions of patients worldwide.Unfortunately,there are no effective medications for mitigating brain injury after ischemic stroke.TRP channels are evolutionally ancient biosensors that detect external stimuli as well as tissue or cellular injury.To date,many members of the TRP superfamily have been reported to contribute to ischemic brain injury,including the TRPC subfamily(1,3,4,5,6,7),TRPV subfamily(1,2,3,4)and TRPM subfamily(2,4,7).These TRP channels share structural similarities but have distinct channel functions and properties.Their activation during ischemic stroke can be beneficial,detrimental,or even both.In this review,we focus on discussing the interesting features of stroke-related TRP channels and summarizing the underlying cellular and molecular mechanisms responsible for their involvement in ischemic brain injury.展开更多
After hypoxia, ischemia, or inflammatory injuries to the central nervous system, the damaged cells release a large amount of adenosine triphosphate, which may cause secondary neuronal death. Autophagy is a form of cel...After hypoxia, ischemia, or inflammatory injuries to the central nervous system, the damaged cells release a large amount of adenosine triphosphate, which may cause secondary neuronal death. Autophagy is a form of cell death that also has neuroprotective effects. Cell Counting Kit assay, monodansylcadaverine staining, flow cytometry, western blotting, and real-time PCR were used to determine the effects of exogenous adenosine triphosphate treatment at different concentrations （2, 4, 6, 8, 10 mmol/L） over time （1, 2, 3, and 6 hours） on the apoptosis and autophagy of SH-SY5Y cells. High concentrations of extracellular adenosine triphosphate induced autophagy and apoptosis of SH-SYSY cells. The enhanced autophagy first appeared, and peaked at 1 hour after treatment with adenosine triphosphate. Cell apoptosis peaked at 3 hours, and persisted through 6 hours. With prolonged exposure to the adenosine triphosphate treatment, the fraction of apoptotic cells increased. These data suggest that the SH-SY5Y neural cells initiated autophagy against apoptosis within an hour of adenosine triphosphate treatment to protect themselves against injury.展开更多
基金supported by the National Key Research and Development Program of China,Nos.2017YFE0122900(to BH),2019YFA0110800(to WL),2019YFA0903802(to YW),2021YFA1101604(to LW),2018YFA0108502(to LF),and 2020YFA0804003(to JW)the National Natural Science Foundation of China,Nos.31621004(to WL,BH)and 31970821(to YW)+1 种基金CAS Project for Young Scientists in Basic Research,No.YSBR-041(to YW)Joint Funds of the National Natural Science Foundation of China,No.U21A20396(to BH)。
文摘Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.
基金supported by the Natural Sciences and Engineering Research Council of Canada(NSERC) Discovery(NSERC 2016040 to DJ,SM and EKFY)+4 种基金University of Waterloo start up fund(to DJ,SM and EKFY) for their generous fundingNSERC Undergraduate Student Research Awards(USRAto SM and EKFY)Collaborative Research and Training Experience(CREATE,401207296to SM and EKFY) for their generous partial funding
文摘Extracellular matrix(ECM)influences cell differentiation through its structural and biochemical properties.In nervous system,neuronal behavior is influenced by these ECMs structures which are present in a meshwork,fibrous,or tubular forms encompassing specific molecular compositions.In addition to contact guidance,ECM composition and structures also exert its effect on neuronal differentiation.This short report reviewed the native ECM structure and composition in central nervous system and peripheral nervous system,and their impact on neural regeneration and neuronal differentiation.Using topographies,stem cells have been differentiated to neurons.Further,focussing on engineered biomimicking topographies,we highlighted the role of anisotropic topographies in stem cell differentiation to neurons and its recent temporal application for efficient neuronal differentiation.
基金supported by NIH NS069726 and NS094539America Heart Association 13GRANT17020004(to SD)
文摘Focal ischemic stroke（FIS）results from the lack of blood flow in a particular region of the brain and accounts for about 80%of all human strokes.Although tremendous efforts have been made in translational research,the treatment strategies are still limited.Tissue plasminogen activator is the only FDA-approved drug currently available for acute stroke treatment,
基金supported by Grants from the National Natural Science Foundation of China(31630039 and 31700666)the Ministry of Science and Technology of China(2017YFA0504203 and 2018YFC1004504)the Science and Technology Commission of Shanghai Municipality(19JC1412500)。
文摘There are more than a thousand trillion specific synaptic connections in the human brain and over a million new specific connections are formed every second during the early years of life. The assembly of these staggeringly complex neuronal circuits requires specific cell-surface molecular tags to endow each neuron with a unique identity code to discriminate self from non-self. The clustered protocadherin(Pcdh) genes, which encode a tremendous diversity of cell-surface assemblies, are candidates for neuronal identity tags. We describe the adaptive evolution,genomic structure, and regulation of expression of the clustered Pcdhs. We specifically focus on the emerging3-D architectural and biophysical mechanisms that generate an enormous number of diverse cell-surface Pcdhs as neural codes in the brain.
文摘Enolase is a multifunctional enzyme primarily involved in catalyzing the conversion of 2-phosphoglycerate to phosphoenolpyruvate during glycolysis and the reverse reaction during gluconeogenesis[1-4].Though typically expressed in the cytosol,enolase has been shown to migrate to the cell surface upon inflammatory signal[3].
基金partially supported by the National Institute of Health(R01-HL143750 and R01NS131661)American Heart Association(19TPA34890022)to LYthe Connecticut Institute for the Brain and Cognitive Sciences Seed Grant(402194)to PZ.
文摘Ischemic stroke is a devastating disease that affects millions of patients worldwide.Unfortunately,there are no effective medications for mitigating brain injury after ischemic stroke.TRP channels are evolutionally ancient biosensors that detect external stimuli as well as tissue or cellular injury.To date,many members of the TRP superfamily have been reported to contribute to ischemic brain injury,including the TRPC subfamily(1,3,4,5,6,7),TRPV subfamily(1,2,3,4)and TRPM subfamily(2,4,7).These TRP channels share structural similarities but have distinct channel functions and properties.Their activation during ischemic stroke can be beneficial,detrimental,or even both.In this review,we focus on discussing the interesting features of stroke-related TRP channels and summarizing the underlying cellular and molecular mechanisms responsible for their involvement in ischemic brain injury.
基金supported by the National Natural Science Foundation of China,No.81371346,81271376
文摘After hypoxia, ischemia, or inflammatory injuries to the central nervous system, the damaged cells release a large amount of adenosine triphosphate, which may cause secondary neuronal death. Autophagy is a form of cell death that also has neuroprotective effects. Cell Counting Kit assay, monodansylcadaverine staining, flow cytometry, western blotting, and real-time PCR were used to determine the effects of exogenous adenosine triphosphate treatment at different concentrations （2, 4, 6, 8, 10 mmol/L） over time （1, 2, 3, and 6 hours） on the apoptosis and autophagy of SH-SY5Y cells. High concentrations of extracellular adenosine triphosphate induced autophagy and apoptosis of SH-SYSY cells. The enhanced autophagy first appeared, and peaked at 1 hour after treatment with adenosine triphosphate. Cell apoptosis peaked at 3 hours, and persisted through 6 hours. With prolonged exposure to the adenosine triphosphate treatment, the fraction of apoptotic cells increased. These data suggest that the SH-SY5Y neural cells initiated autophagy against apoptosis within an hour of adenosine triphosphate treatment to protect themselves against injury.
