Lycium barbarum polysaccharides(LBPs)are the major polysaccharides extracted from L.barbarum,which is used in traditional Chinese medicine(TCM)for treating diseases.Studies have shown that LBPs have important biologic...Lycium barbarum polysaccharides(LBPs)are the major polysaccharides extracted from L.barbarum,which is used in traditional Chinese medicine(TCM)for treating diseases.Studies have shown that LBPs have important biological activities,such as antioxidation,anti-aging,neuroprotection,immune regulation.LBPs inhibit oxidative stress,improve neurodegeneration and stroke-induced neural injury,increase proliferation and differentiation of neural stem cell,and promote neural regeneration.Here we have reviewed latest advances in the biomedical activities of LBPs and improved methods for the isolation,extraction,and purification of LBPs.Then,new discoveries to decrease oxidative stress and cellular apoptosis,inhibit aging progress,and improve neural repair in neurodegeneration and ischemic brain injury have been discussed in detail through in vitro cell culture and in vivo animal studies.Importantly,the molecular mechanisms of LBPs in playing neuroprotective roles are further explored.Lastly,we discuss the perspective of LBPs as biomedical compounds in TCM and modern medicine and provide the experimental and theoretical evidence to use LBPs for the treatment of aging-related neurological diseases and stroke-induced neural injuries.展开更多
Adopted by the 2nd IANR Annual Conference General Assembly,Beijing,China,April 2009 and amended by the:8th IANR Annual Conference General Assembly,Tehran,Iran,April 201514th IANR Annual Conference,Xi'an,China,Marc...Adopted by the 2nd IANR Annual Conference General Assembly,Beijing,China,April 2009 and amended by the:8th IANR Annual Conference General Assembly,Tehran,Iran,April 201514th IANR Annual Conference,Xi'an,China,March 20231.With the rapid advancement of basic and clinical research in neurorestoration,Neurorestoratology has become a distinct medical discipline based on both the neurorestorative potential findings and neurorestorable theory of the central nervous system(CNS).Several relevant academic organizations,institutions,clinical centers and departments have been established worldwide,and many guidelines and expert consensus documents have been released for the purpose of promoting CNS restoration.The International Association of Neurorestoratology(IANR)is one of the most important academic platforms for this discipline.展开更多
Induced pluripotent stem cells(iPSCs)have become the leading research object in the clinical application of restorative medicine.They are easily generated from diverse cell sources and functionally indistinguishable f...Induced pluripotent stem cells(iPSCs)have become the leading research object in the clinical application of restorative medicine.They are easily generated from diverse cell sources and functionally indistinguishable from embryonic stem cells without the accompanying ethical issues.To date,the use of iPSC-derived neural stem cells and their progeny in the treatment of neurodegenerative and injurious diseases has achieved good results,with great potential in cell drug development.However,because of some unique biological properties and differences from traditional drug production processes,cell drug research and development has many problems that can hinder clinical applications.Given this situation,the Chinese Association of Neurorestoratology(Preparatory)and China Committee of the International Association of Neurorestoratology have organized relevant professional experts to formulate the standard presented here.Overall,the aim was to promote the clinical application of neural stem cells(NSCs)and their further derived neural cells from iPSC sources and promote cell drugs’production and development.This standard refers to the latest research results,quality evaluation criteria for traditional medicines,and the regulatory framework for cellular treatments.The standard considers general biological properties of cells,including cell morphology,cell cycle,karyotype,and cell viability.The specific biological properties of NSCs,such as cell surface markers and differentiation ability,general drug standards,such as aseptic testing,endotoxins,human virus detection,and cell-related drug standards,such as telomerase activity and tumorigenicity,are also considered.This standard will serve as a reference for physicians and scientists who focus on clinical nervous cell applications and studies related to iPSCs.展开更多
Progressive neurodegenerative diseases(NDs)that lack effective disease-modifying treatments,including Alzheimer's disease(AD),Parkinson's disease(PD),amyotrophic lateral sclerosis(ALS),and Huntington's dis...Progressive neurodegenerative diseases(NDs)that lack effective disease-modifying treatments,including Alzheimer's disease(AD),Parkinson's disease(PD),amyotrophic lateral sclerosis(ALS),and Huntington's disease(HD),represent significant global health challenges.In recent years,key research findings have included the role of neuroinflammation driven by microglia and astrocytes,the impact of genetic mutations,and the importance of autophagy and mitochondrial quality control in maintaining neuronal health.In this review,we summarize recent advancements of the pathogenesis of NDs,the cellular and animal models that have provided valuable insights into disease mechanisms,and the development of blood-based biomarkers for early diagnosis and monitoring of disease progression.We also highlight emerging neurorestorative therapeutic strategies involving stem cell therapy,antisense oligonucleotides,and induced pluripotent stem cells.Additionally,we cover recent clinical trials of promising drugs,such as lecanemab and donanemab for AD,and tavapadon for PD.Finally,we propose future research directions,emphasizing the need for combination therapies that target multiple pathways,the development of more precise animal models,and the integration of nanotechnology for improved drug delivery across the blood–brain barrier.展开更多
There was much progress in the field of Neurorestoratology in the year of 2022.It included highlighting advances in understanding the pathogenesis of neurological diseases,neurorestorative mechanisms,and clinical trea...There was much progress in the field of Neurorestoratology in the year of 2022.It included highlighting advances in understanding the pathogenesis of neurological diseases,neurorestorative mechanisms,and clinical treatments as compiled in the 2022 yearbook of Neurorestoratology.There is still controversy about whether amyloid b-protein and tau protein deposition are the reasons for or the results of Alzheimer's disease(AD)pathology.The fabricated images in important key articles that speculated on the reasons for AD pathogenesis were found.Cholinergic deficiency and decrease or loss in strength of glutamatergic synapse,limited or failing bidirectional cholinergic upregulation in early cognitive impairment,or progressive posterior-to-anterior cortical cholinergic denervation could result in the appearance of AD.Exploration of neurorestorative mechanisms were found in more detail ways in neuromodulation,immunomodulation,neurogenesis,neural network or circuitry reconstruction,neuroprotection,nervous structural repair,and neuroplasticity.Several kinds of cell therapies for neurological diseases showed neurorestorative effects in open-label and/or non-randomized clinical studies or trials.However,mesenchymal stromal cells and mononuclear cells did not demonstrate neurorestorative effects or improve the quality of life for patients with neurodegenerative diseases or neurotrauma including stroke,spinal cord injury(SCI),and amyotrophic lateral sclerosis in randomized,double-blind,placebo-controlled clinical trials(RDPCTs).Clinical treatments through neurostimulation/neuromodulation and the brainecomputer/machine interface yielded positive results in AD,Parkinson's disease,stroke,SCI,cerebral palsy,and other diseases in RDPCTs.Neurorestorative surgery,pharmaceutical neurorestorative therapy and other interventions have demonstrated neurorestorative effects for various considered incurable neurological diseases in RDPCTs.Thus,this year,additional guidelines,assessment scales,and standards were set up or revised.These included guidelines of clinical neurorestorative treatments for brain trauma(2022 China version),clinical cell therapy guidelines for neurorestoration(IANR/CANR 2022),SCI or dysfunction quality of life rating scale(SCIDQLRS)(IANR 2022 version).Neurorestorative effects of varying therapeutic strategies with higher standards of evidence-based medicine are now benefiting patients with currently incurable neurological diseases.Hopefully some of them may become routine therapeutic interventions for patients with these diseases in the near future.展开更多
In order to promote the clinical use of neural progenitor or precursor cells for treating neurological diseases and damage, we need to standardize culture procedures for these cells. The Chinese Association of Neurore...In order to promote the clinical use of neural progenitor or precursor cells for treating neurological diseases and damage, we need to standardize culture procedures for these cells. The Chinese Association of Neurorestoratology put forward these standards for training operators, standardized use and management of materials and equipment, standardized isolation and culture for neural progenitor/precursor cells, and the standardized management in preservation, transport, and related safe operation procedures of the neural progenitors. These cultures and quality control standards also include the Good Manufacturing Practice environment, routine maintenance as well as the monitoring and reporting of the clinical‐grade neural progenitor cells. The aim of these standards is to improve the therapeutic efficacy and minimize the possible side effects from lake of quality control.展开更多
Time is infinite movement in constant motion.We are glad to see that Neurorestoratology,a new discipline,has grown into a rich field involving many global researchers in recent years.In this 2019 yearbook of Neurorest...Time is infinite movement in constant motion.We are glad to see that Neurorestoratology,a new discipline,has grown into a rich field involving many global researchers in recent years.In this 2019 yearbook of Neurorestoratology,we introduce the most recent advances and achievements in this field,including findings on the pathogenesis of neurological diseases,neurorestorative mechanisms,and clinical therapeutic achievements globally.Many patients have benefited from treatments involving cell therapies,neurostimulation/neuromodulation,brain–computer interface,neurorestorative surgery or pharmacy,and many others.Clinical physicians can refer to this yearbook with the latest knowledge and apply it to clinical practice.展开更多
Cell therapy has been shown to be a crucial clinical therapeutic option for central nervous system diseases or damage.Promoting standardization of clinical cell therapy procedures is essential for professional associa...Cell therapy has been shown to be a crucial clinical therapeutic option for central nervous system diseases or damage.Promoting standardization of clinical cell therapy procedures is essential for professional associations devoted to cell therapy.The International Association of Neurorestoratology(IANR)and the Chinese Association of Neurorestoratology(CANR;Preparatory)collaborated to release Clinical Cell Therapy Guidelines for Neurorestoration(IANR/CANR 2017)in 2018.Due to recent advances and achievements in clinical cell therapy worldwide in recent years,IANR and CANR have renewed and updated the guidelines.Except for the requirements of equipment,personnel,and ethics,these revised guidelines include cell type nomenclature,cell quality control,cell types in clinical application,minimal suggested cellular doses,patient-informed consent,indications and contraindications for undergoing cell therapy,documentation of procedure and therapy,safety evaluation,efficacy evaluation,the policy of repeated treatments,do not charge patients for unproven therapies,basic principles of cell therapy,and publishing responsibility.IANR/CANR recommends that all clinical practitioners follow these cellular therapy guidelines.These guidelines provide references of better cell types,doses,routes,and therapeutic timing windows in different diseases.展开更多
Parkinson’s disease(PD)is one of the most common neurodegenerative disorders of aging,characterized by the degeneration of dopamine neurons(DA neurons)in the substantial nigra,leading to the advent of both motor symp...Parkinson’s disease(PD)is one of the most common neurodegenerative disorders of aging,characterized by the degeneration of dopamine neurons(DA neurons)in the substantial nigra,leading to the advent of both motor symptoms and non-motor symptoms.Current treatments include electrical stimulation of the affected brain areas and dopamine replacement therapy.Even though both categories are effective in treating PD patients,the disease progression cannot be stopped.The research advance into cell therapies provides exciting potential for the treatment of PD.Current cell sources include neural stem cells(NSCs)from fetal brain tissues,human embryonic stem cells(hESCs),induced pluripotent stem cells(iPSCs)and directly induced dopamine neurons(iDA neurons).Here,we evaluate the research progress in different cell sources with a focus on using iPSCs as a valuable source and propose key challenges for developing cells suitable for large-scale clinical applications in the treatment of PD.展开更多
Alzheimer’s disease(AD)is the most prevalent age-related neurodegenerative disease which is mainly caused by aggregated protein plaques in degenerating neurons of the brain.These aggregated protein plaques are mainly...Alzheimer’s disease(AD)is the most prevalent age-related neurodegenerative disease which is mainly caused by aggregated protein plaques in degenerating neurons of the brain.These aggregated protein plaques are mainly consisting of amyloidβ(Aβ)fibrils and neurofibrillary tangles(NFTs)of phosphorylated tau protein.Even though the transgenic murine models can recapitulate some of the AD phenotypes,they are not the human cell models of AD.Recent breakthrough in somatic cell reprogramming made it available to use induced pluripotent stem cells(i PSCs)for patientspecific disease modeling and autologous transplantation therapy.Human i PSCs provide alternative ways to obtain specific human brain cells of AD patients to study the molecular mechanisms and therapeutic approaches for familial and sporadic forms of AD.After differentiation into neuronal cells,i PSCs have enabled the investigation of the complex aetiology and timescale over which AD develops in human brain.Here,we first go over the pathological process of and transgenic models of AD.Then we discuss the application of i PSC for disease model and cell transplantation.At last the challenges and future applications of i PSCs for AD will be summarized to propose cell-based approaches for the treatment of this devastating disorder.展开更多
Objective: Parkinson's disease(PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine(DA) neurons in the substantia nigra in the midbrain. Experimental and cli...Objective: Parkinson's disease(PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine(DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells(NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods: NSCs were isolated from 14‐week‐old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers: βⅢ‐tubulin and microtubule‐associated protein 2(neurons), tyrosine hydroxylase(DA neurons), and glial fibrillary acidic protein(glial cells). After a 6‐hydroxydopamine(6‐OHDA)‐lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6‐OHDA‐lesioned PD rats. Results: The motor behaviors of the PD rats were assessed by the number of apomorphine‐induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine‐induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions: Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.展开更多
文摘Lycium barbarum polysaccharides(LBPs)are the major polysaccharides extracted from L.barbarum,which is used in traditional Chinese medicine(TCM)for treating diseases.Studies have shown that LBPs have important biological activities,such as antioxidation,anti-aging,neuroprotection,immune regulation.LBPs inhibit oxidative stress,improve neurodegeneration and stroke-induced neural injury,increase proliferation and differentiation of neural stem cell,and promote neural regeneration.Here we have reviewed latest advances in the biomedical activities of LBPs and improved methods for the isolation,extraction,and purification of LBPs.Then,new discoveries to decrease oxidative stress and cellular apoptosis,inhibit aging progress,and improve neural repair in neurodegeneration and ischemic brain injury have been discussed in detail through in vitro cell culture and in vivo animal studies.Importantly,the molecular mechanisms of LBPs in playing neuroprotective roles are further explored.Lastly,we discuss the perspective of LBPs as biomedical compounds in TCM and modern medicine and provide the experimental and theoretical evidence to use LBPs for the treatment of aging-related neurological diseases and stroke-induced neural injuries.
文摘Adopted by the 2nd IANR Annual Conference General Assembly,Beijing,China,April 2009 and amended by the:8th IANR Annual Conference General Assembly,Tehran,Iran,April 201514th IANR Annual Conference,Xi'an,China,March 20231.With the rapid advancement of basic and clinical research in neurorestoration,Neurorestoratology has become a distinct medical discipline based on both the neurorestorative potential findings and neurorestorable theory of the central nervous system(CNS).Several relevant academic organizations,institutions,clinical centers and departments have been established worldwide,and many guidelines and expert consensus documents have been released for the purpose of promoting CNS restoration.The International Association of Neurorestoratology(IANR)is one of the most important academic platforms for this discipline.
文摘Induced pluripotent stem cells(iPSCs)have become the leading research object in the clinical application of restorative medicine.They are easily generated from diverse cell sources and functionally indistinguishable from embryonic stem cells without the accompanying ethical issues.To date,the use of iPSC-derived neural stem cells and their progeny in the treatment of neurodegenerative and injurious diseases has achieved good results,with great potential in cell drug development.However,because of some unique biological properties and differences from traditional drug production processes,cell drug research and development has many problems that can hinder clinical applications.Given this situation,the Chinese Association of Neurorestoratology(Preparatory)and China Committee of the International Association of Neurorestoratology have organized relevant professional experts to formulate the standard presented here.Overall,the aim was to promote the clinical application of neural stem cells(NSCs)and their further derived neural cells from iPSC sources and promote cell drugs’production and development.This standard refers to the latest research results,quality evaluation criteria for traditional medicines,and the regulatory framework for cellular treatments.The standard considers general biological properties of cells,including cell morphology,cell cycle,karyotype,and cell viability.The specific biological properties of NSCs,such as cell surface markers and differentiation ability,general drug standards,such as aseptic testing,endotoxins,human virus detection,and cell-related drug standards,such as telomerase activity and tumorigenicity,are also considered.This standard will serve as a reference for physicians and scientists who focus on clinical nervous cell applications and studies related to iPSCs.
基金Project of Hubei Key Laboratory of Cognitive and Affective Disorders(HBCAD2024-13).
文摘Progressive neurodegenerative diseases(NDs)that lack effective disease-modifying treatments,including Alzheimer's disease(AD),Parkinson's disease(PD),amyotrophic lateral sclerosis(ALS),and Huntington's disease(HD),represent significant global health challenges.In recent years,key research findings have included the role of neuroinflammation driven by microglia and astrocytes,the impact of genetic mutations,and the importance of autophagy and mitochondrial quality control in maintaining neuronal health.In this review,we summarize recent advancements of the pathogenesis of NDs,the cellular and animal models that have provided valuable insights into disease mechanisms,and the development of blood-based biomarkers for early diagnosis and monitoring of disease progression.We also highlight emerging neurorestorative therapeutic strategies involving stem cell therapy,antisense oligonucleotides,and induced pluripotent stem cells.Additionally,we cover recent clinical trials of promising drugs,such as lecanemab and donanemab for AD,and tavapadon for PD.Finally,we propose future research directions,emphasizing the need for combination therapies that target multiple pathways,the development of more precise animal models,and the integration of nanotechnology for improved drug delivery across the blood–brain barrier.
文摘There was much progress in the field of Neurorestoratology in the year of 2022.It included highlighting advances in understanding the pathogenesis of neurological diseases,neurorestorative mechanisms,and clinical treatments as compiled in the 2022 yearbook of Neurorestoratology.There is still controversy about whether amyloid b-protein and tau protein deposition are the reasons for or the results of Alzheimer's disease(AD)pathology.The fabricated images in important key articles that speculated on the reasons for AD pathogenesis were found.Cholinergic deficiency and decrease or loss in strength of glutamatergic synapse,limited or failing bidirectional cholinergic upregulation in early cognitive impairment,or progressive posterior-to-anterior cortical cholinergic denervation could result in the appearance of AD.Exploration of neurorestorative mechanisms were found in more detail ways in neuromodulation,immunomodulation,neurogenesis,neural network or circuitry reconstruction,neuroprotection,nervous structural repair,and neuroplasticity.Several kinds of cell therapies for neurological diseases showed neurorestorative effects in open-label and/or non-randomized clinical studies or trials.However,mesenchymal stromal cells and mononuclear cells did not demonstrate neurorestorative effects or improve the quality of life for patients with neurodegenerative diseases or neurotrauma including stroke,spinal cord injury(SCI),and amyotrophic lateral sclerosis in randomized,double-blind,placebo-controlled clinical trials(RDPCTs).Clinical treatments through neurostimulation/neuromodulation and the brainecomputer/machine interface yielded positive results in AD,Parkinson's disease,stroke,SCI,cerebral palsy,and other diseases in RDPCTs.Neurorestorative surgery,pharmaceutical neurorestorative therapy and other interventions have demonstrated neurorestorative effects for various considered incurable neurological diseases in RDPCTs.Thus,this year,additional guidelines,assessment scales,and standards were set up or revised.These included guidelines of clinical neurorestorative treatments for brain trauma(2022 China version),clinical cell therapy guidelines for neurorestoration(IANR/CANR 2022),SCI or dysfunction quality of life rating scale(SCIDQLRS)(IANR 2022 version).Neurorestorative effects of varying therapeutic strategies with higher standards of evidence-based medicine are now benefiting patients with currently incurable neurological diseases.Hopefully some of them may become routine therapeutic interventions for patients with these diseases in the near future.
文摘In order to promote the clinical use of neural progenitor or precursor cells for treating neurological diseases and damage, we need to standardize culture procedures for these cells. The Chinese Association of Neurorestoratology put forward these standards for training operators, standardized use and management of materials and equipment, standardized isolation and culture for neural progenitor/precursor cells, and the standardized management in preservation, transport, and related safe operation procedures of the neural progenitors. These cultures and quality control standards also include the Good Manufacturing Practice environment, routine maintenance as well as the monitoring and reporting of the clinical‐grade neural progenitor cells. The aim of these standards is to improve the therapeutic efficacy and minimize the possible side effects from lake of quality control.
文摘Time is infinite movement in constant motion.We are glad to see that Neurorestoratology,a new discipline,has grown into a rich field involving many global researchers in recent years.In this 2019 yearbook of Neurorestoratology,we introduce the most recent advances and achievements in this field,including findings on the pathogenesis of neurological diseases,neurorestorative mechanisms,and clinical therapeutic achievements globally.Many patients have benefited from treatments involving cell therapies,neurostimulation/neuromodulation,brain–computer interface,neurorestorative surgery or pharmacy,and many others.Clinical physicians can refer to this yearbook with the latest knowledge and apply it to clinical practice.
基金On behalf of International Association of Neurorestoratology(IANR)and Chinese Association of Neurorestoratology(CANR,Preparatory)。
文摘Cell therapy has been shown to be a crucial clinical therapeutic option for central nervous system diseases or damage.Promoting standardization of clinical cell therapy procedures is essential for professional associations devoted to cell therapy.The International Association of Neurorestoratology(IANR)and the Chinese Association of Neurorestoratology(CANR;Preparatory)collaborated to release Clinical Cell Therapy Guidelines for Neurorestoration(IANR/CANR 2017)in 2018.Due to recent advances and achievements in clinical cell therapy worldwide in recent years,IANR and CANR have renewed and updated the guidelines.Except for the requirements of equipment,personnel,and ethics,these revised guidelines include cell type nomenclature,cell quality control,cell types in clinical application,minimal suggested cellular doses,patient-informed consent,indications and contraindications for undergoing cell therapy,documentation of procedure and therapy,safety evaluation,efficacy evaluation,the policy of repeated treatments,do not charge patients for unproven therapies,basic principles of cell therapy,and publishing responsibility.IANR/CANR recommends that all clinical practitioners follow these cellular therapy guidelines.These guidelines provide references of better cell types,doses,routes,and therapeutic timing windows in different diseases.
基金by National Natural Science Foundation of China(NSFC 81271251)The Science and Technology Developmental Fund of Shandong Province,China(2012GGA15049).
文摘Parkinson’s disease(PD)is one of the most common neurodegenerative disorders of aging,characterized by the degeneration of dopamine neurons(DA neurons)in the substantial nigra,leading to the advent of both motor symptoms and non-motor symptoms.Current treatments include electrical stimulation of the affected brain areas and dopamine replacement therapy.Even though both categories are effective in treating PD patients,the disease progression cannot be stopped.The research advance into cell therapies provides exciting potential for the treatment of PD.Current cell sources include neural stem cells(NSCs)from fetal brain tissues,human embryonic stem cells(hESCs),induced pluripotent stem cells(iPSCs)and directly induced dopamine neurons(iDA neurons).Here,we evaluate the research progress in different cell sources with a focus on using iPSCs as a valuable source and propose key challenges for developing cells suitable for large-scale clinical applications in the treatment of PD.
基金supported by National Natural Science Foundation of China(NSFC 81571241)Research Start Fund of Shandong University of Traditional Chinese Medicine(2018-220259).
文摘Alzheimer’s disease(AD)is the most prevalent age-related neurodegenerative disease which is mainly caused by aggregated protein plaques in degenerating neurons of the brain.These aggregated protein plaques are mainly consisting of amyloidβ(Aβ)fibrils and neurofibrillary tangles(NFTs)of phosphorylated tau protein.Even though the transgenic murine models can recapitulate some of the AD phenotypes,they are not the human cell models of AD.Recent breakthrough in somatic cell reprogramming made it available to use induced pluripotent stem cells(i PSCs)for patientspecific disease modeling and autologous transplantation therapy.Human i PSCs provide alternative ways to obtain specific human brain cells of AD patients to study the molecular mechanisms and therapeutic approaches for familial and sporadic forms of AD.After differentiation into neuronal cells,i PSCs have enabled the investigation of the complex aetiology and timescale over which AD develops in human brain.Here,we first go over the pathological process of and transgenic models of AD.Then we discuss the application of i PSC for disease model and cell transplantation.At last the challenges and future applications of i PSCs for AD will be summarized to propose cell-based approaches for the treatment of this devastating disorder.
基金supported by the National Natural Science Foundation of China (NSFC, No. 81271251)
文摘Objective: Parkinson's disease(PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine(DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells(NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods: NSCs were isolated from 14‐week‐old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers: βⅢ‐tubulin and microtubule‐associated protein 2(neurons), tyrosine hydroxylase(DA neurons), and glial fibrillary acidic protein(glial cells). After a 6‐hydroxydopamine(6‐OHDA)‐lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6‐OHDA‐lesioned PD rats. Results: The motor behaviors of the PD rats were assessed by the number of apomorphine‐induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine‐induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions: Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.
