成髓鞘细胞研究和应用进展课件

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1、安逸生活 pk 艰苦卓绝创业高原如此艰苦的环境：勇于担当，发挥引领作用高原如此艰苦的环境：勇于担当，发挥引领作用以苦为乐，人生需要有一股精神以苦为乐，人生需要有一股精神2016.10.11. 中英脱髓鞘伦敦会议中英脱髓鞘伦敦会议1.1.一一些些基基本本概概念念与与影影像像学学检检查查2.2.儿儿童童脱脱髓髓鞘鞘疾疾病病临临床床分分类类3.3.成成髓髓鞘鞘细细胞胞分分类类4.4.神神经经修修复复的的路路径径5.5.各各种种细细胞胞近近期期研研究究一一览览02040608010012013579 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39Year 19

2、77 2016 40年年 demyelination remyelination Pubmed文献量趋势图文献量趋势图体体成成分分中中脂脂类类占占70%, 蛋蛋白白质质占占30%构构成成髓髓鞘鞘蛋蛋白白质质主主要要两两种种成成分：分：蛋蛋白白脂脂蛋蛋白白( PLP)和和髓髓鞘鞘碱碱性性蛋蛋白白(MBP) 髓鞘相关糖蛋白(MAG) 髓鞘少突胶质细胞糖蛋白(MOG) Wolfram 蛋白脂 DM 准大小蛋白 其他微量蛋白绝绝缘缘，避免干扰 相邻轴突之间 轴突与其他结构之间加快动作电位传递：“跳跳跃跃式式传传导导”机制引导受损轴突：再再生生cells (Schwann cellsand oligod

3、endrocytes) co-operate with the axon in the formation and maintenance of myelin sheaths.中枢神经系统中枢神经系统(CNS)(CNS)有髓神经纤维有髓神经纤维与周围与周围(PNS)(PNS)相似结构相似结构u有髓鞘和郎飞结u髓鞘外无基膜（神经膜）u相邻神经纤维有时融合（箭头）要集中在：出生后18个月内（1.5年）1岁岁半半接近成人oligodendrocyte少突胶质细胞：大大多多数数细细胞胞5-10年年成成熟，熟，存存活活50年。年。每每年年减减少少1-300 OLS The final stage of

4、oligodendrocyte development is myelination. Unlike the peripheral nervous system where there is a strict size-dependent bias for myelination (only axons 1 um diameter enjoy the privilege), in the CNS axons as small as 300 nm are sometimes myelinated. Nevertheless, CNS myelination is also influenced

5、by axonal size. Surprisingly, cultured oligodendrocytes will begin myelinating even synthetic axon-like tubes lacking the usual neuron-glia signaling cues. In this type of blind myelination, only tubes with a diameter of 400 nm were myelinated, suggesting this mode of myelination may be particularly

6、 important for larger axons. Moreover, once differentiating, it appears that oligodendrocytes only have a very narrow window of opportunity to select which adjacent axons to myelinate (5 h in the developing zebrafish and 12 h in myelinating cultures of rodent derived cells), irrespective of the tota

7、l number of sheaths being made. This implies that the signaling pathways mediating this process are likely to be relatively robust. Although in vitro studies have implicated several key pathways, to date no one single molecule has been shown to be indispensable for myelination of CNS axons in vivo,

8、highlighting the great degree of redundancy in the control of this vital process. Despite this, recent in vivo studies have revealed a great deal about how these various signaling pathways converge to control the extent or timing of myelination, if not overall myelination per se.髓鞘脱失（脱髓鞘）一种very常见的临床

9、神经病理变化多指数多指数T2/磁化转移磁化转移MRIprovides an important step for understanding typical myelin development as well as providing the ability to identify when and where white matter abnormalities occur in neurodevelopmental disorders.myelin water volume fraction (MVF)髓磷脂体积分数髓磷脂体积分数myelin water fraction (MWF)髓磷

10、脂水分围性和中枢性u周周围围性性脱脱髓髓鞘鞘病：病：多以双下肢或四肢瘫痪为首发u中中枢枢性性脱脱髓髓鞘鞘病：病：以视力障碍、肢体无力、发热、抽搐、头痛等为首发on can occurin the damaged central nervous system (CNS)的存活纤维发生脱脱髓髓鞘鞘尽管有些轴突保持着解剖上的完整，但已无生理功能损伤部位远端的轴突出现华华勒勒变变性性Franklin RJ, et al.1997njury is accompanied by chronicprogressive demyelinationl oligodendrocyte progenitor cel

11、l proliferationl generation of new oligodendrocytesl formation of thinner myelinDomingues et al.2016.Domingues et al.2016.l First research on transplantation of myelin-forming cells into the demyelinated spinal cord l The cells survive, migrate, and find axons that need myelin insulation, and remyel

12、inate them l thereby restoring ability to conduct impulsesStephen Waxman and Jeffery KocsisOlfactory ensheathing cell (OEC) 嗅鞘细胞嗅鞘细胞Remyelination雪雪旺旺细细胞胞雪雪旺旺细细胞胞雪雪旺旺细细胞胞卒卒中中Oligodendrocyte少突胶质细胞少突胶质细胞Oligodendrocyte precursor cells (OPCs), a subpopulation that accounts for 5 to 8% of cells within th

13、e central nervous system, are potential sources of oligodendrocyte replacement after SCI. OPCs react rapidly to injuries, proliferate at a high rate, and can differentiate into myelinating oligodendrocytes. However, posttraumatic endogenous remyelination is rarely complete.011) Neural stem cell (NSC

14、) 神经干细胞神经干细胞Adipose mesenchymal stem cell脂肪来源间充质干细胞脂肪来源间充质干细胞ility of Human Adipose-Derived Stem Cells to Alleviate Symptoms in the Experimental Autoimmune Encephalomyelitis Mouse Modelonors failedto ameliorate the neurodegeneration associated with EAE, and mice treated with older donor cells had in

15、creased CNS inflammation, demyelination, splenocyte proliferation in vitro compared with the mice receiving cells from younger donors.STEM CELLS TRANSLATIONALMEDICINE 2013;2:797n of human adipose-derived stem cells enhances remyelination in lysolecithin-induced focal demyelination of rat spinal cord

16、. Mol Biotechnol. 2014 .DSCs) into a lysophosphatidylcholine (lysolecithin) model of multiple sclerosis (MS) and determined the efficiency of these cells in remyelination process. Forty adult rats were randomly divided into control, lysolecithin, vehicle, and transplantation groups, and focal demyel

17、ination was induced by lysolecithin injection into spinal cord. To assess motor performance, all rats were examined weekly with a standard EAE scoring scale. Four weeks after cell transplantation, to assess the extent of demyelination and remyelination, Luxol Fast Blue staining was used. In addition

18、, immunohistochemistry technique was used for assessment of the presence of oligodendrocyte phenotype cells in damaged spinal cord. hADSCs had ability to differentiate into oligodendrocyte phenotype cells and improved remyelination process. Moreover, the evaluation of rat motor functions showed that

19、 animals which were treated with hADSC compared to other groups had significant improvement. hADSCs transplantation for cell-based therapies may play a proper cell source in the treatment of neurodegenerative diseases such as MS.Cord blood derived cell脐带血细胞脐带血细胞Skin derived precursor cell皮肤干细胞皮肤干细胞2015Embryonic stem (ES) cell胚胎干细胞胚胎干细胞Bone marrow-derived MSC骨髓基质细胞骨髓基质细胞(BM-MSC)Umbilical cord-derived mesenchymal stromal cell脐带来源间充质基质细胞脐带来源间充质基质细胞 iPS cell多能诱导干细胞多能诱导干细胞 Schwann cell雪旺细胞雪旺细胞therapyOmmya囊）全麻下显微镜下脊髓内移植局麻下CT引导脊髓内移植局部蛛网膜下腔移植（小脑延髓池）腰椎穿刺静脉移植动脉介入经鼻粘膜思考题思考题