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1 Journal of Clinical Rehabilitative Tissue Engineering Research March 5, 2009 Vol.13, No.10 Research progress in stem cell transplantation for treating amyotrophic lateral sclerosis Liu Qiang, Lu Xi-lin, Yao Xiao-li Department of Neurology, First Liu Qiang, Studying for master s degree, Department of Neurology, First liuqiangsh@ 126.com Correspondence to: Yao Xiao-li, Doctor, Associate professor, Department of Neurology, First yeyaoxiaoli@ sohu.com Received: Accepted: liuqiangsh@ 126.com yeyaoxiaoli@ sohu.com : R394.2 : A : (2009) ( / ZS Q) Abstract: Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that targets motor neurons without efficient treatment. Stem cell receives the enormous attention because it from specific tissues can differentiate into motor neuron. Stem cells from specific tissues could be used for amyotrophic lateral sclerosis, such as embryonic stem cells, neural stem cells, bone marrow mesenchymal stem cells, umbilical cord blood-derived stem cells and induced pluripotent stem cells. The mechanism of stem-cell therapy includes cell-replacement, delivery neurotrophic factors and immunomodulation. Animal researches and some clinical trails have confirmed that stem cells have great potential to treat neurodegenerative diseases. Till now, people are still unknown some aspects of stem cells, and many problems still need to be resolved. Liu Q, Lu XL, Yao XL.Research progress in stem cell transplantation for treating amyotrophic lateral sclerosis. Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2009;13(10): [ [J] (10): [ 0 (riluzole) Glu 3 FDA [1] [2] 1 3 cell-replacement trophic factors delivery immunomodulation 3 [3] /2008 Pubmed P.O. Box 1200, Shenyang cn.zglckf.com

2 . amyotrophic lateral sclerosis stem cells Meta embryonic stem cell somatic stem cell inner cell mass ICM primordial germ cell PGC [4] neural stem cell NSCs [5] mesenchymal stem cells MSCs [6] [7] umbilical cord blood-derived stem cells UBCs [1] [8] CSF [9] induced pluripotent stem cells ips [10] 4.2 [11] [11] camp [12] [11] Nakamura [13] Erb [14] 18 Kerr [15] NPCs 3 [16] Wu [17] [18] [19] Jin [19-20] 1.5% Habisch [9] ISSN CN /R CODEN: ZLKHAH 1943

3 10 d 4 [9] Mazzini [21] 7 T 7-9 3~6 MRI 4 FVC ALS-FRS 50% [22] Terao [23-24] [25] [2] SOD1 SOD1 [26] SOD1 [27-28] SOD1 SOD1 [29]. SOD1 14 d 50% SOD1 [30] [31] 10 [11] SOD1 [32] Kerr [15] SOD1 [33] 1 [34] [35] [36] [37] 1944 P.O. Box 1200, Shenyang cn.zglckf.com

4 . [38] hnpc 100% 30% 30% hnpc [39] SOD1 [40] SOD1 hnpc [39] 4.4 McGeer [41] minocycline [42] CD4 CD4 2 CD4 D8 [43] [25] [44] Ryan [45] 5 6 [1] Miller RG, Mitchell JD, Lyon M, et al. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev.2007;(1):CD [2] Nirmalananthan N, Greensmith L. Amyotrophic lateral sclerosis: recent advances and future therapies. Curr Opin Neurol.2005;18(6): [3] Kan I, Melamed E, Offen D. Autotransplantation of bone marrow-derived stem cells as a therapy for neurodegenerative diseases. Handb Exp Pharmacol. 2007;(180): [4] Christou YA, Moore HD, Shaw PJ, et al. Embryonic stem cells and prospects for their use in regenerative medicine approaches to motor neurone disease. Neuropathol Appl Neurobiol. 2007;33(5): [5] Taupin P. Adult neural stem cells, neurogenic niches, and cellular therapy. Stem Cell Rev. 2006;2(3): [6] Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy. 2005;7(1): [7] Krabbe C, Zimmer J, Meyer M. Neural transdifferentiation of mesenchymal stem cells--a critical review. APMIS. 2005;113(11-12): [8] Zigova T, Song S, Willing AE, et al. Human umbilical cord blood cells express neural antigens after transplantation into the developing rat brain. Cell Transplant. 2002;11(3): [9] Habisch HJ, Janowski M, Binder D, et al. Intrathecal application of neuroectodermally converted stem cells into a mouse model of ALS: limited intraparenchymal migration and survival narrows therapeutic effects. J Neural Transm. 2007;114(11): [10] Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858): [11] Conti L, Reitano E, Cattaneo E. Neural stem cell systems: diversities and properties after transplantation in animal models of diseases. Brain Pathol. 2006;16(2): [12] Harper JM, Krishnan C, Darman JS, et al. Axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult rats. Proc Natl Acad Sci USA. 2004;101(18): [13] Nakamura M, Okano H, Toyama Y, et al. Transplantation of embryonic spinal cord-derived neurospheres support growth of supraspinal projections and functional recovery after spinal cord injury in the neonatal rat. J Neurosci Res. 2005;81(4): [14] Erb DE, Mora RJ, Bunge RP. Reinnervation of adult rat gastrocnemius muscle by embryonic motoneurons transplanted into the axotomized tibial nerve. Exp Neurol 1993;124(2): [15] Kerr DA, Llado J, Shamblott MJ, et al. Human embryonic germ cell derivatives facilitate motor recovery of rats with diffuse motor neuron injury. J Neurosci. 2003;23(12): [16] Gage FH. Mammalian neural stem cells. Science. 2000;287(5457): [17] Wu P, Tarasenko YI, Gu Y, et al. Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat. Nat Neurosci. 2002;5(12): [18] Beyer Nardi N, da Silva Meirelles L. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol. 2006;(174): ISSN CN /R CODEN: ZLKHAH 1945

5 [19] Jin HK, Carter JE, Huntley GW, et al. Intracerebral transplantation of mesenchymal stem cells into acid sphingomyelinase-deficient mice delays the onset of neurological abnormalities and extends their life span. J Clin Invest. 2002;109(9): [20] Garbuzova-Davis S, Willing AE, Zigova T, et al. Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. J Hematother Stem Cell Res. 2003;12(3): [21] Mazzini L, Fagioli F, Boccaletti R, et al. Stem cell therapy in amyotrophic lateral sclerosis: A methodological approach in humans. Amyotroph Lateral Scler Other Motor Neuron Disord. 2003;4(3): [22] Mazzini L, Mareschi K, Ferrero I, et al. Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral sclerosis. Neurol Res 2006;28(5): [23] Terao S, Sobue G, Hashizume Y, et al. Disease-specific patterns of neuronal loss in the spinal ventral horn in amyotrophic lateral sclerosis, multiple system atrophy and X-linked recessive bulbospinal neuronopathy, with special reference to the loss of small neurons in the intermediate zone. J Neurol. 1994;241(4): [24] Marsala M, Kakinohana O, Yaksh TL, et al. Spinal implantation of hnt neurons and neuronal precursors: graft survival and functional effects in rats with ischemic spastic paraplegia. Eur J Neurosci. 2004;20(9): [25] Hedlund E, Hefferan MP, Marsala M, et al. Cell therapy and stem cells in animal models of motor neuron disorders. Eur J Neurosci. 2007;26(7): [26] Clement AM, Nguyen MD, Roberts EA, et al. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science. 2003;302(5642): [27] Pramatarova A, Lagani re J, Roussel J,et al. Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment. J Neurosci. 2001;21(10): [28] Lino MM, Schneider C, Caroni P. Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease. J Neurosci. 2002;22(12): [29] Di Giorgio FP, Carrasco MA, Siao MC, et al. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci. 2007;10(5): [30] Nagai M, Re DB, Nagata T, et al. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci. 2007;10(5): [31] Nayak MS, Kim YS, Goldman M, et al. Cellular therapies in motor neuron diseases. Biochim Biophys Acta. 2006;1762(11-12): [32] Liu Z, Martin LJ. The adult neural stem and progenitor cell niche is altered in amyotrophic lateral sclerosis mouse brain. J Comp Neurol. 2006;497(3): [33] Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med. 2004;10 (Suppl):S10-S17. [34] Storkebaum E, Lambrechts D, Dewerchin M, et al. Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS. Nat Neurosci. 2005;8(1): [35] Lu P, Jones LL, Snyder EY,et al. Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp Neurol. 2003;181(2): [36] Akiyama Y, Honmou O, Kato T,et al. Transplantation of clonal neural precursor cells derived from adult human brain establishes functional peripheral myelin in the rat spinal cord. Exp Neurol. 2001;167(1): [37] Kablar B, Belliveau AC. Presence of neurotrophic factors in skeletal muscle correlates with survival of spinal cord motor neurons. Dev Dyn. 2005;234(3): [38] Mohajeri MH, Figlewicz DA, Bohn MC. Intramuscular grafts of myoblasts genetically modified to secrete glial cell line-derived neurotrophic factor prevent motoneuron loss and disease progression in a mouse model of familial amyotrophic lateral sclerosis. Hum Gene Ther. 1999;10(11): [39] Suzuki M, McHugh J, Tork C, et al. GDNF secreting human neural progenitor cells protect dying motor neurons, but not their projection to muscle, in a rat model of familial ALS. PLoS ONE. 2007;2(1):e689. [40] Hall ED, Oostveen JA, Gurney ME. Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS. Glia. 1998;23(3): [41] McGeer PL, McGeer EG. Inflammatory processes in amyotrophic lateral sclerosis. Muscle Nerve. 2002;26(4): [42] Zhang W, Narayanan M, Friedlander RM. Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann Neurol. 2003;53(2): [43] Yan J, Xu L, Welsh AM, et al. Combined immunosuppressive agents or CD4 antibodies prolong survival of human neural stem cell grafts and improve disease outcomes in amyotrophic lateral sclerosis transgenic mice. Stem Cells. 2006;24(8): [44] Corcione A, Benvenuto F, Ferretti E, et al. Human mesenchymal stem cells modulate B-cell functions. Blood. 2006;107(1): [45] Ryan JM, Barry FP, Murphy JM, et al. Mesenchymal stem cells avoid allogeneic rejection. J Inflamm. (Lond) P.O. Box 1200, Shenyang cn.zglckf.com

Microsoft Word - 932-937王艳6.0-G.DOC

Microsoft Word - 932-937王艳6.0-G.DOC 中国组织工程研究第 18 卷第 6 期 2014 02 05 出版 Chinese Journal of Tissue Engineering Research February 5, 2014 Vol.18, No.6 脐带间充质干细胞治疗帕金森病的应用王艳 1, 赵新利 2, 张军艳 1, 谭军 1 ( 1 新乡医学院第