《神经退行性疾病干细胞移植治疗：目前研究现状与未来展望_ppt课件》由会员分享，可在线阅读，更多相关《神经退行性疾病干细胞移植治疗：目前研究现状与未来展望_ppt课件（39页珍藏版）》请在金锄头文库上搜索。
1、韩发彬，MD，PhD 泰山医学院聊城临床学院 干细胞与再生医学实验室 2015，10，31,神经退行性疾病干细胞移植治疗：目前研究现状与未来展望,Stem Cell Sources for Treatmentof Neurological Diseases (AD, PD, ALS, MS, Stroke, SCI),Fabin Han, et al, Journal of Neurorestoratology 2015:3 112,胎儿神经干细胞治疗帕金森氏病临床研究发展历程,Evans JR, Mason SL, Barker RA. Prog Brain Res. 2012;200:16
2、9-98,Lindvall O, et al，Nat Med. 2008 May;14(5):501-3,TH,Synuclein,Overlay,Transplanted fetal mesencephalic dopaminergic neurons (11-16 years) developed alpha-synuclein-positive Lewy bodies in grafted neurons,Synuclein-Host,Ubiquintin-Host,Synuclein-Grafted Neurons,Ubiquintin-Grafted Neurons,Grafted
3、nigral neurons were found to have Lewy body-like inclusions14 years after transplantation into the striatum of an individual with PD,Olanow CW. et al Nat Med. 2008May;14(5):504-6.,Transplanted dopamine neurons in people with PD do not contain Lewy bodies,Mendez, Isacson et al, , NATURE MEDICINE VOLU
4、ME 14 (5):507-509, 2008,Improved Cell Therapy Protocol for Parkinsons Disease Based on Differentiation Efficiency and Safety of hESC-, Hipsc and Non-Human Primate iPSC-Derived DA Neurons,Isacson et al, , Stem Cells. 2013 ;31(8):1548-62.,Dopamine release from transplanted neural stem cells in Parkins
5、onian rat striatum in vivo.,Zhou z, et al, Proc Natl Acad Sci U S A.2014 Nov 4;111(44):15804-9,iPSC-Derived Dopamine Neurons function after Transplantation in a Non-Human Primate Model of Parkinsons Disease,Cell Stem Cell. 2015 Mar 5;16(3):269-74. Ole Isacson et al，Harvard Stem Cell Institute,Stem c
6、ell-based Clinical Trials for (ALS),Nuralstem, In c . the first Phase I clinical trial for a stem cell-based treatment of ALS. Initiated in 2010 and completed in 2013, involved the transplan-tation of human spinal cord-derived NSCs into the spinal cord of 15 late to mid-stage ALS patients,Glass, Fel
7、dman, E.L., 2012. Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: results of a phase I trial in 12 patients. Stem Cells 30 (6), 1144 1151.Riley, J., Feldman, E.L., 2014. “Intraspinal stem cell transplantation in ALS: a phase I trial, cervical microin
8、jection and final surgical safety outcomes”. Neurosurgery 74 (1), 77 87,RESULTS: Unilateral cervical (group D, n = 3) and cervical plus thoracolumbar (group E, n = 3) microinjections to the ventral horn have been completed in ambulatory patients. One patient developed a postoperative kyphotic deform
9、ity prompting completion of a laminoplasty in subsequent patients. Another required reoperation for wound dehiscence and infection. The solitary patient with bulbar amyotrophic lateral sclerosis required perioperative reintubation. CONCLUSION: Delivery of a cellular payload to the cervical or thorac
10、olumbar spinal cord was well tolerated by the spinal cord in this vulnerable population. This encouraging finding supports consideration of this delivery approach for neurodegenerative, oncologic, and traumatic spinal cord afflictions.,Intraspinal stem cell transplantation in ALS: a phase I trial, 2
11、014,iPS Cells Were Generated from PD patients and Normal Controls,6-OHDA-induced Rat PD Model,Human iPS cells Integrated to the Host Brain of 6-OHDA-induced Rat PD Model,Han F, Wang W, Chen C, Duan J, et al Cytotherapy 2015,分化的胎脑神经干细胞移植治疗PD,建立大鼠SCI损伤模型,A. 暴露和部分横切脊髓外科手术。 B. T7 横断损伤产生后肢瘫痪。 C. 无脊髓损伤的正常
12、大鼠。,RT-PCR to Detect the MicroRNA Expression in Rat SCI Model,Real-Time RT-PCR to Detect the MicroRNA Expression in SCI,干细胞移植修复脊髓神经损伤,移植神经干细胞分化的神经轴索与宿主脊髓神经细胞及其树突形成突触连接,Lu P et al，Cell. 2012 September 14; 150(6): 12641273,Bone Marrow Stromal Cell Intraspinal Transplants Fail to Improve Motor Outcomes
13、 in a Severe Model of SCI,Journal of Neurotrauma 2015， Tuszynski MH To determine whether local mechanisms mediate BMSC neuroprotective actions grafted allogeneic BMSCs to sites of severe, compressive spinal cord injury (SCI) in Sprague Dawley rats. Cells were administered 48 hours after the original
14、 injury. Additional animals received allogeneic MSCs that were genetically modified to secrete BDNF, to further determine whether a locally administered neurotrophic factor provides or extends neuroprotection. two months post-injury in a clinically relevant model of severe SCI, BMSC grafts with or w
15、ithout BDNF secretion failed to improve motor outcomes. Thus, allogeneic grafts of BMSCs do not appear to act through local mechanisms, and future clinical trials that acutely deliver BMSCs to actual sites of injury within days are unlikely to be beneficial.,Intraspinal Stem Cell Transplantation in
16、Amyotrophic Lateral Sclerosis: A Phase I Safety Trial, Technical Note, and Lumbar Safety Outcomes NEUROSURGERY VOLUME 71 | NUMBER 2 | AUGUST 2012Department of Neurosurgery, Emory University , Atlanta , Georgia ; Department of Neurology, Emory University, Atlanta, Georgia; Department of Neurology, Un
17、iversity of Michigan, Ann Arbor, Michigan,神经干细胞移植方法,Each microinjection series comprised 5 injections (10mL/injection) separated by 4 mm. Each injection :100 000 neural stem cells derived from a fetal spinal cord. Twelve patients were treated with either unilateral or bilateral injections.Patients are followed clinically and radiologically to assess potential toxicity of the procedure.,
