骨髓间充质干细胞的分化潜能及其对创伤性脑损伤治疗的研究进展

骨髓间充质干细胞(Bone Marrow Derived Mesenchymal Stem Cells,MSCs）是一种存在于骨髓中的组织干细胞,能够分泌多种造血调控因子及细胞外基质的组织干细胞,具有自我增殖和多向分化潜能,可以向中枢神经细胞分化,包括神经元细胞、星形胶质细胞和少突胶质细胞等。骨髓间充质干细胞还具有易于培养,免疫性低等特点,已被广泛应用于治疗创伤性脑损伤疾病的细胞移植研究。     

神经干细胞移植治疗Alzheimer病

阿尔茨海默病是一种中枢神经系统进行性变性疾病,为痴呆的常见原因,其较明确的病理变化是前脑胆碱能投射系统胆碱能神经元变性、细胞数量减少。神经干细胞具有自我更新和多分化潜能属性,可分化成神经元、星形胶质细胞和少突胶质细胞。神经干细胞移植后可分化成胆碱能神经元,有潜力替代AD病程中丢失的细胞,从而达到治疗疾病的目的。     

影响神经干细胞定向分化因素的研究进展

神经干细胞(NSC)具有自我更新和多分化潜能属性,可分化产生神经元、星形胶质细胞和少突胶质细胞,这使得NSC移植替代神经系统疾病中丢失的细胞成为可能.NSC在胚胎和成体中枢神经系统均存在.NSC移植在体内环境下(尤其是非神经发生区域)绝大多数分化成胶质细胞(星形胶质细胞),有可能会加重胶质瘢痕形成.在中枢神经系统疾病的NSC细胞替代治疗策略中,NSC分化成合适的细胞类型显得格外重要.现就影响NSC定向分化的因素作一综述.     

影响多发性硬化髓鞘再生的因素及其机制

多发性硬化(MS)是常见的中枢神经系统(CNS)炎性脱髓鞘性疾病,目前认为MS是一种自身免疫性疾病,是细胞免疫与体液免疫共同参与导致的以脑和脊髓白质损伤为主的疾病.由于在人类成体前脑有大量少突胶质细胞前体细胞(OPC),另外在MS脱髓鞘斑内亦存在OPC,少突胶质细胞及其前体OPC是MS中髓鞘再生的主要来源.目前越来越多的研究认为髓鞘再生是MS治疗中非常有前景的方向,但是要达到有效的、有治疗作用的髓鞘再生,首先必须了解影响髓鞘再生的各种因素,理解控制髓鞘形成和髓鞘再生的确切机制.现就近年来这方面的研究进展综述如下.     

神经干细胞体外培养定向分化为多巴胺能神经元相关因子的研究

神经干细胞(neural stem cell,NSCs)是一类具有分裂潜能和自我更新能力的母细胞,并具有分化为神经元、星形胶质细胞和少突胶质细胞的能力,存在于中枢神经系统多个部位。神经干细胞的最直接应用是利用神经干细胞的多方向分化潜能特性,进行神经干细胞的移植,以恢复宿主的中枢神经系统的正常结构和功能。由于细胞移植治疗需要相当     

神经干细胞对创伤性颅脑损伤治疗的研究进展

神经干细胞(neural stem cell,NSCs)是一类具有分裂潜能和自我更新能力的母细胞,在不同的诱导情况下可以分化成不同的神经细胞,其中包括神经元细胞、胶质细胞、少突胶质细胞等,神经干细胞在颅脑损伤的研究中有了很大的进展,但是还有很多问题亟待解决,本文主要介绍神经干细胞对外伤性颅脑损伤治疗的研究进展,探讨神经干细胞在治疗脑外伤存在的问题。     

以急性症状性癫痫发作起病的MOG抗体相关皮质脑炎2例

髓鞘少突胶质细胞糖蛋白(myelin oligodendrocyte gly-coprotein,MOG)IgG 抗体相关疾病(MOG-IgG associated disorders,MOGAD)是近年来提出的一种免疫介导的中枢神经系统炎性脱髓鞘疾病,是不同于多发性硬化(multiple sclerosis,MS)和...     

细胞凋亡在多发性硬化中的作用及其机制

多发性硬化(MS)是一种以中枢神经系统脱髓鞘病变为特征的自身免疫性疾病。在MS及其动物模型—实验性自身免疫性脑脊髓炎,细胞凋亡参与了自身反应性T细胞的清除和脑细胞(少突胶质细胞、巨噬细胞、小胶质细胞等)的损伤、修复,其机制可能是通过Fas/FasL系统、内源性皮质醇等途径。对凋亡过程的干预有可能成为一种治疗MS的新策略。     

神经干细胞增殖和分化相关信号通路的研究进展

神经干细胞（neuralstemcells,NSCs）是一类来源于中枢神经系统的干细胞,具有自我更新能力及分化为神经元、星形胶质细胞和少突胶质细胞的潜能,为中枢神经系统损伤和退行性疾病的治疗提供了新的治疗选择。但如何让NSCs在复杂的信号网络调控中实现有序的增殖、分化,修复受损的神经组织,目前研究还未完全清楚。本文对涉及NSCs增殖和分化相关信号通路的最新进展做一综述。     

4℃低温保存对神经干细胞活性的影响

神经干细胞（neuralstemcells,NSCs）是一群来源于神经组织的细胞,具有连续增殖、定向分化、迁移并与宿主细胞形成功能联系的特性。NSCs在适当条件下可分化成神经元、少突胶质细胞和星型胶质细胞。NSCs的发现标志着神经科学领域的重大突破,在治疗神经系统损伤以及多种神经系统疾病方面具有广阔的临床应用前景。     

Neural stem cell‐based treatment for neurodegenerative diseases

Human neurodegenrative diseases such as Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are caused by a loss of neurons and glia in the brain or spinal cord. Neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and stem cell‐based cell therapies for neurodegenerative diseases have been developed. A recent advance in generatioin of a new class of pluripotent stem cells, induced pluripotent stem cells (iPSCs), derived from patients' own skin fibroblasts, opens doors for a totally new field of personalized medicine. Transplantation of NSCs, neurons or glia generated from stem cells in animal models of neurodegenrative diseases, including PD, HD, ALS and AD, demonstrates clinical improvement and also life extension of these animals. Additional therapeutic benefits in these animals can be provided by stem cell‐mediated gene transfer of therapeutic genes such as neurotrophic factors and enzymes. Although further research is still needed, cell and gene therapy based on stem cells, particularly using neurons and glia derived from iPSCs, ESCs or NSCs, will become a routine treatment for patients suffering from neurodegenerative diseases and also stroke and spinal cord injury.     

Stem cell challenges in the treatment of neurodegenerative disease

Neurodegenerative diseases result from the gradual and progressive loss of neural cells and lead to nervous system dysfunction. The rapidly advancing stem cell field is providing attractive alternative options for fighting these diseases. Results have provided proof of principle that cell replacement can work in humans with Parkinson's disease (PD). However, three clinical studies of cell transplantation were published that found no net benefit, while patients in two of the studies developed dyskinesias that persisted despite reductions in treatment. Induced pluripotent stem cells (iPSC) have major potential advantages because patient-specific neuroblasts are suitable for transplantation, avoid immune reactions, and can be produced without the use of human ES cells (hESC). Although iPSCs have not been successfully used in clinical trials for PD, patients with amyotrophic lateral sclerosis (ALS) were treated with autologous stem cells and, though they had some degree of decline one year after treatment, they were still improved compared with the preoperative period or without any drug therapy. In addition, neural stem cells (NSCs), via brain-derived neurotrophic factor (BDNF), have been shown to ameliorate complex behavioral deficits associated with widespread Alzheimer's disease (AD) pathology in a transgenic mouse model of AD. So far, the FDA lists 18 clinical trials treating multiple sclerosis (MS), but most are in preliminary stages. This article serves as an overview of recent studies in stem cell and regenerative approaches to the above chronic neurodegenerative disorders. There are still many obstacles to the use of stem cells as a cure for neurodegenerative disease, especially because we still don't fully understand the true mechanisms of these diseases. However, there is hope in the potential of stem cells to help us learn and understand a great deal more about the mechanisms underlying these devastating neurodegenerative diseases.     

Cell Therapy for Multiple Sclerosis

The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.     

Stem cell therapy for Parkinson's disease: safety and modeling

For decades,clinicians have developed medications and therapies to alleviate the symptoms of Parkinson’s disease,but no treatment currently can slow or even stop the progression of this localized neurodegeneration.Fortunately,sparked by the genetic revolution,stem cell reprogramming research and the advancing capabilities of personalization in medicine enable forward-thinking to unprecedented patient-specific modeling and cell therapies for Parkinson’s disease using induced pluripotent stem cells(iPSCs).In addition to modeling Parkinson’s disease more accurately than chemically-induced animal models,patient-specific stem cell lines can be created,elucidating the effects of genetic susceptibility and sub-populations’differing responses to in vitro treatments.Sourcing cell therapy with iPSC lines provides ethical advantages because these stem cell lines do not require the sacrifice of human zygotes and genetically-specific drug trails can be tested in vitro without lasting damage to patients.In hopes of finally slowing the progression of Parkinson’s disease or re-establishing function,iPSC lines can ultimately be corrected with gene therapy and used as cell sources for neural transplantation for Parkinson’s disease.With relatively localized neural degeneration,similar to spinal column injury,Parkinson’s disease presents a better candidacy for cell therapy when compared to other diffuse degeneration found in Alzheimer’s or Huntington’s Disease.Neurosurgical implantation of pluripotent cells poses the risk of an innate immune response and tumorigenesis.Precautions,therefore,must be taken to ensure cell line quality before transplantation.While cell quality can be quantified using a number of assays,a yielding a high percentage of therapeutically relevant dopaminergic neurons,minimal de novo genetic mutations,and standard chromosomal structure is of the utmost importance.Current techniques focus on iPSCs because they can be matched with donors using human leukocyte antigens,thereby reducing the severity and risk of immune rejection.In August of 2018,researchers in Kyoto,Japan embarked on the first human clinical trial using iPSC cell therapy transplantation for patients with moderate Parkinson’s disease.Transplantation of many cell sources has already proven to reduce Parkinson’s disease symptoms in mouse and primate models.Here we discuss the history and implications for cell therapy for Parkinson’s disease,as well as the necessary safety standards needed for using iPSC transplantation to slow or halt the progression of Parkinson’s disease.     

Application of behavioral therapies in adult and adolescent patients with chronic migraine

Spinal cord injury (SCI) is induced by a variety of damages such as trauma, ischemia, and iatrogenic injury, resulting in sense and motion dysfunction. Despite the improvements in medical and surgical care, current treatment methods for SCI demonstrate poor and delayed efficiency, leading to different degree of permanent loss of neural function and disability in the patients. Rapid advances in stem-cells research suggest that stem cells may be applied in SCI therapy. Indeed, SCI is a major field in which stem-cell therapy has been proposed and practised, and most recently the clinical trials of stem-cell therapy were initiated, which aroused a number of clinical concerns. In this review, we summarize current status of SCI repair, then introduce the sources and biological characteristics of induced pluripotent stem cells (iPSCs), and discuss the differentiation potential of iPSCs and the perspective of the application of iPSCs in SCI therapy.     

Self-Organized Cerebellar Tissue from Human Pluripotent Stem Cells and Disease Modeling with Patient-Derived iPSCs

Recent advances in the techniques that differentiate induced pluripotent stem cells (iPSCs) into specific types of cells enabled us to establish in vitro cell-based models as a platform for drug discovery. iPSC-derived disease models are advantageous to generation of a large number of cells required for high-throughput screening. Furthermore, disease-relevant cells differentiated from patient-derived iPSCs are expected to recapitulate the disorder-specific pathogenesis and physiology in vitro. Such disease-relevant cells will be useful for developing effective therapies. We demonstrated that cerebellar tissues are generated from human PSCs (hPSCs) in 3D culture systems that recapitulate the in vivo microenvironments associated with the isthmic organizer. Recently, we have succeeded in generation of spinocerebellar ataxia (SCA) patient-derived Purkinje cells by combining the iPSC technology and the self-organizing stem cell 3D culture technology. We demonstrated that SCA6-derived Purkinje cells exhibit vulnerability to triiodothyronine depletion, which is suppressed by treatment with thyrotropin-releasing hormone and Riluzole. We further discuss applications of patient-specific iPSCs to intractable cerebellar disease.     

诱导型多能干细胞在神经变性疾病中的作用

诱导型多能干细胞技术是一种通过新的体细胞重编程,将组织细胞转化为可多向分化的细胞即干细胞的技术。目前已将4种转录因子导入人体皮肤纤维母细胞,并首次成功诱导出诱导型多能干细胞。此项技术不但可以建立神经系统疾病动物模型,用于发病机制和致病基因的研究,而且可以开展移植研究,验证疗效及筛选药物。