Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous ...Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenes展开更多
Orthobiologics is a subset of regenerative medicine, which focuses on treating the musculoskeletal system. The main therapeutics utilized include platelet-rich plasma, stem cells, exosomes, and scaffolding matrices. C...Orthobiologics is a subset of regenerative medicine, which focuses on treating the musculoskeletal system. The main therapeutics utilized include platelet-rich plasma, stem cells, exosomes, and scaffolding matrices. Continuous discoveries and new innovations have led to an increase in both popularity and usage of these therapeutics by various medical and scientific communities. Despite its potential, however, the field is viewed with significant skepticism secondary to poor documentation, a lack of standardization, vague nomenclature, disorganized research protocols, and an absence of a clear understanding of the mechanisms underlying the effects of the various therapeutics. This ambiguity led to a surge in direct-to-consumer marketing by “Stem Cell Clinics”, putting patient’s health at risk and further delegitimizing the field. These shortcomings led to a recent push for standardization by both professionals and organizations alike;a move that has put Orthobiologics on the path toward becoming a guideline-driven, protocol-based, and research-backed specialty. And with these rapid changes comes the need for an updated definition of “Orthobiologics”, a crucial element of any legitimate and standardized medical field.展开更多
Activation of neuroprotective and particularly later neurorestorative mechanisms after stroke attempts to restore or compensate for lost functions.This potentially opens a wide window for restorative therapies to prom...Activation of neuroprotective and particularly later neurorestorative mechanisms after stroke attempts to restore or compensate for lost functions.This potentially opens a wide window for restorative therapies to promote brain repair and improve long-term functional recovery.Although extensively demonstrated in the preclinical setting,the efficacy of cell-based therapies in stroke patients has been modest at best,if any at all.Translational failure may be due to the ineffective survival and integration of transplanted cells in pro-death stroke microenvironments that are not conducive for the structural reconstruction of damaged brain tissue and repair-related network reorganization.Optimal systemic delivery,timing,cell product,and dose remain open as well.Fortunately,a better understanding of the brain plasticity mechanisms underlying stroke recovery has ushered in a combination approach of cell-based therapy and rehabilitation that is aimed at achieving additive,synergistic,or even maximal beneficial effects.This novel combination therapy is not only targeted at promoting exogenous and endogenous cell survival and augmenting stand-alone restorative mechanisms but also at utilizing rehabilitation to facilitate a graft–host structural and functional integration and plasticity that would effectively remodel stroke tissue and restitute lost functions.This review presents an overview of the combination of cell-based therapy and experimental rehabilitation in stroke models.It also discusses associated shortcomings as well as proposes strategies to address them and help facilitate the advancement of this combination approach.展开更多
Very little is known about the effects of transcranial magnetic stimulation and rehabilitation training on pyramidal cell dendrites and synapses of the contralateral, unaffected sensorimotor cortex in a rat model of f...Very little is known about the effects of transcranial magnetic stimulation and rehabilitation training on pyramidal cell dendrites and synapses of the contralateral, unaffected sensorimotor cortex in a rat model of focal cerebral infarct. The present study was designed to explore the mechanisms underlying improved motor function via transcranial magnetic stimulation and rehabilitation training following cerebral infarction. Results showed that rehabilitation training or transcranial magnetic stimulation alone reduced neurological impairment in rats following cerebral infarction, as well as significantly increased synaptic curvatures and post-synaptic density in the non-injured cerebral hemisphere sensorimotor cortex and narrowed the synapse cleft width. In addition, the percentage of perforated synapses increased. The combination of transcranial magnetic stimulation and rehabilitation resulted in significantly increased total dendritic length, dendritic branching points, and dendritic density in layer V pyramidal cells of the non-injured cerebral hemisphere motor cortex. These results demonstrated that transcranial magnetic stimulation and rehabilitation training altered structural parameters of pyramidal cell dendrites and synapses in the non-injured cerebral hemisphere sensorimotor cortex, thereby improving the ability to compensate for neurological functions in rats following cerebral infarction.展开更多
Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of ...Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site,orchestrate the differentiation process, and promote the integration of neural circuitry for functional rehabilitation.All these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.展开更多
Objective:The following article explores our evolving understandings of the role of regenerative technology as an effective penile rehabilitation tool in men with erectile dysfunction(ED)in the setting of prostate can...Objective:The following article explores our evolving understandings of the role of regenerative technology as an effective penile rehabilitation tool in men with erectile dysfunction(ED)in the setting of prostate cancer(PCa)treatment and PCa survivorship.Methods:This narrative clinical review paper summarizes what is currently known about various modalities of regenerative therapy in restoring spontaneous erectile function(EF)in men following PCa treatment with an emphasis on penile rehabilitation strategies.Results:Conventional medical therapy often does not reverse underlying endothelial dysfunction or promote neuro-vasculogenesis to preserve penile health in men with ED.Over the past decade,there has been considerable interest in the role of regenerative therapy to restore endothelial dysfunction and ED without future dependency on medical therapy.Regenerative therapy can be classified into cellular-based(immunomodulators,stem cells,and platelet-rich plasma),biomaterials(nerve graft transfer),and device-related technology(low-intensity shockwave).Although published literature shows early promise in the role of regenerative technology for ED,there is a paucity of high-quality clinical trials in the setting of penile rehabilitation and PCa survivorship to support their use as standard care and be adopted in clinical guidelines.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81672261(to XH),81972151(to HZ),82372568(to JL)the Natural Science Foundation of Guangdong Province,Nos.2019A1515011106(to HZ),2023A1515030080(to JL)。
文摘Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenes
文摘Orthobiologics is a subset of regenerative medicine, which focuses on treating the musculoskeletal system. The main therapeutics utilized include platelet-rich plasma, stem cells, exosomes, and scaffolding matrices. Continuous discoveries and new innovations have led to an increase in both popularity and usage of these therapeutics by various medical and scientific communities. Despite its potential, however, the field is viewed with significant skepticism secondary to poor documentation, a lack of standardization, vague nomenclature, disorganized research protocols, and an absence of a clear understanding of the mechanisms underlying the effects of the various therapeutics. This ambiguity led to a surge in direct-to-consumer marketing by “Stem Cell Clinics”, putting patient’s health at risk and further delegitimizing the field. These shortcomings led to a recent push for standardization by both professionals and organizations alike;a move that has put Orthobiologics on the path toward becoming a guideline-driven, protocol-based, and research-backed specialty. And with these rapid changes comes the need for an updated definition of “Orthobiologics”, a crucial element of any legitimate and standardized medical field.
基金European Commission under the Horizon 2020 program,Grant/Award Number:681044。
文摘Activation of neuroprotective and particularly later neurorestorative mechanisms after stroke attempts to restore or compensate for lost functions.This potentially opens a wide window for restorative therapies to promote brain repair and improve long-term functional recovery.Although extensively demonstrated in the preclinical setting,the efficacy of cell-based therapies in stroke patients has been modest at best,if any at all.Translational failure may be due to the ineffective survival and integration of transplanted cells in pro-death stroke microenvironments that are not conducive for the structural reconstruction of damaged brain tissue and repair-related network reorganization.Optimal systemic delivery,timing,cell product,and dose remain open as well.Fortunately,a better understanding of the brain plasticity mechanisms underlying stroke recovery has ushered in a combination approach of cell-based therapy and rehabilitation that is aimed at achieving additive,synergistic,or even maximal beneficial effects.This novel combination therapy is not only targeted at promoting exogenous and endogenous cell survival and augmenting stand-alone restorative mechanisms but also at utilizing rehabilitation to facilitate a graft–host structural and functional integration and plasticity that would effectively remodel stroke tissue and restitute lost functions.This review presents an overview of the combination of cell-based therapy and experimental rehabilitation in stroke models.It also discusses associated shortcomings as well as proposes strategies to address them and help facilitate the advancement of this combination approach.
基金Yantai Science and Technology Development Projects, No. 2008142-5
文摘Very little is known about the effects of transcranial magnetic stimulation and rehabilitation training on pyramidal cell dendrites and synapses of the contralateral, unaffected sensorimotor cortex in a rat model of focal cerebral infarct. The present study was designed to explore the mechanisms underlying improved motor function via transcranial magnetic stimulation and rehabilitation training following cerebral infarction. Results showed that rehabilitation training or transcranial magnetic stimulation alone reduced neurological impairment in rats following cerebral infarction, as well as significantly increased synaptic curvatures and post-synaptic density in the non-injured cerebral hemisphere sensorimotor cortex and narrowed the synapse cleft width. In addition, the percentage of perforated synapses increased. The combination of transcranial magnetic stimulation and rehabilitation resulted in significantly increased total dendritic length, dendritic branching points, and dendritic density in layer V pyramidal cells of the non-injured cerebral hemisphere motor cortex. These results demonstrated that transcranial magnetic stimulation and rehabilitation training altered structural parameters of pyramidal cell dendrites and synapses in the non-injured cerebral hemisphere sensorimotor cortex, thereby improving the ability to compensate for neurological functions in rats following cerebral infarction.
基金supported by the National Key R&D Program of China (No. 2020YFA0113600 and 2017YFA0105201)National Natural Sciences Foundation of China (81822017 and 32070955)。
文摘Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site,orchestrate the differentiation process, and promote the integration of neural circuitry for functional rehabilitation.All these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.
文摘Objective:The following article explores our evolving understandings of the role of regenerative technology as an effective penile rehabilitation tool in men with erectile dysfunction(ED)in the setting of prostate cancer(PCa)treatment and PCa survivorship.Methods:This narrative clinical review paper summarizes what is currently known about various modalities of regenerative therapy in restoring spontaneous erectile function(EF)in men following PCa treatment with an emphasis on penile rehabilitation strategies.Results:Conventional medical therapy often does not reverse underlying endothelial dysfunction or promote neuro-vasculogenesis to preserve penile health in men with ED.Over the past decade,there has been considerable interest in the role of regenerative therapy to restore endothelial dysfunction and ED without future dependency on medical therapy.Regenerative therapy can be classified into cellular-based(immunomodulators,stem cells,and platelet-rich plasma),biomaterials(nerve graft transfer),and device-related technology(low-intensity shockwave).Although published literature shows early promise in the role of regenerative technology for ED,there is a paucity of high-quality clinical trials in the setting of penile rehabilitation and PCa survivorship to support their use as standard care and be adopted in clinical guidelines.
