人神经前体细胞移植治疗重度脑瘫患儿疗效观察

刘卫鹏; 屈素清; 栾佐; 龚小军; 汪兆艳

PDF(917 KB)

中国当代儿科杂志 ›› 2012, Vol. 14 ›› Issue (10) : 759-762.

论著·临床研究

人神经前体细胞移植治疗重度脑瘫患儿疗效观察

刘卫鹏，屈素清，栾佐，龚小军，汪兆艳

作者信息 +

Treatment of cerebral palsy with transplantation of human neural progenitor cells

LIU Wei-Peng, QU Su-Qing, LUAN Zuo, GONG Xiao-Jun, WANG Zhao-Yan

Author information +

文章历史 +

摘要

目的：观察人神经前体细胞（human neural progenitor cells, hNPCs）移植治疗重度脑性瘫痪（cerebral palsy, CP）患儿的临床疗效。方法：45例重度CP患儿自愿接受hNPCs移植治疗。取孕10~12周人胚胎脑细胞，经体外培养扩增为人神经干细胞球，在超声引导下经侧脑室穿刺注入患儿脑室。49例接受常规康复治疗的重度CP患儿作为对照组。结果：移植后疗效最早出现的1例患儿于术后3 d睡眠、激惹、肌张力明显改善，大部分患儿于术后1个月出现明显改善，3~6个月疗效逐渐减缓。移植组患儿术后1年粗大运动、精细动作及认知发育水平均明显优于对照组。移植治疗后无1例患儿出现危及生命或导致患儿生活质量较术前下降的并发症，移植5年以上随访未见肿瘤发生。结论：hNPCs移植治疗重度CP是一种新的、安全有效的方法，值得进一步研究探索。

Abstract

OBJECTIVE: To study the clinical efficacy of transplantation of human neural progenitor cells (hNPCs) in the treatment of severe cerebral palsy (CP) in children. METHODS: Forty-five children with CP were voluntarily accepted transplantation of hNPCs. The cells obtained from the forebrain of 10 to 12-week-fetus were cultured and amplified into hNPCs. Then the hNPCs were injected into the cerebral ventricle of the patients with the supersonic guidance. RESULTS: Dyssomnia, irritability and muscular tension were improved in one patient 3 days after transplantation. The clinical improvements were observed in the majority of the patients 1 month after transplantation. The therapeutic effects slowed down 3 to 6 months after transplantation. One year after transplantation the gross and fine motor skills and the congnition ability in the transplantation group were considerably surpassed to those in the control group. No delayed severe complications were observed after transplantation. No tumorigenesis was noted 5 years after transplantation. CONCLUSIONS: The transplantation of hNPCs as a novel therapy is effective and safe for severe CP. Many investigations are needed to evaluate the effect of the therapy.

导出引用

刘卫鹏，屈素清，栾佐，龚小军，汪兆艳. 人神经前体细胞移植治疗重度脑瘫患儿疗效观察[J]. 中国当代儿科杂志. 2012, 14(10): 759-762

LIU Wei-Peng, QU Su-Qing, LUAN Zuo, GONG Xiao-Jun, WANG Zhao-Yan. Treatment of cerebral palsy with transplantation of human neural progenitor cells[J]. Chinese Journal of Contemporary Pediatrics. 2012, 14(10): 759-762

中图分类号： R651

参考文献

［1］沈晓明，王卫平.儿科学［M］. 第7版.北京：人民卫生出版社, 2008：373.

［2］Blair E. Epidemiology of the cerebral palsies［J］. Orthop Clin North Am, 2010, 41(4): 441-455.

［3］Madhavan L, Daley BF, Paumier KL, Collier TJ. Transplantation of subventricular zone neural precursors induces an endogenous precursor cell response in a rat model of Parkinson′s disease［J］. J Comp Neurol, 2009, 515(1): 102-115.

［4］Bachoud-Lévi AC, Gaura V, Brugières P, Lefaucheur JP, Boissé MF, Maison P, et al. Effect of fetal neural transplants in patients with Huntington′s disease 6 years after surgery: a long-term follow-up study［J］. Lancet Neurol, 2006, 5(4): 303-309.

［5］Keene CD, Sonnen JA, Swanson PD, Kopyov O, Leverenz JB, Bird TD, et al. Neural transplantation in Huntington disease: long-term grafts in two patients［J］. Neurology, 2007, 68(24): 2093-2098.

［6］Freeman TB, Cicchetti F, Hauser RA, Deacon TW, Li XJ, Hersch SM, et al. Transplanted fetal striatum in Huntington′s disease: phenotypic development and lack of pathology［J］. Proc Natl Acad Sci U S A, 2000, 97(25): 13877-13882.

［7］Krystkowiak P, Gaura V, Labalette M, Rialland A, Remy P, Peschanski M, et al. Alloimmunisation to donor antigens and immune rejection following foetal neural grafts to the brain in patients with Huntington′s disease［J］. PLoS One, 2007, 2(1): e166.

［8］栾佐，尹国才，胡晓红，屈素清，吴南海，严凤清，等. 人神经干细胞移植治疗重度新生儿缺氧缺血性脑病一例［J］.中华儿科杂志,2005，43(8): 580-583.

［9］屈素清，栾佐，刘卫鹏，席小辉，汪兆艳.人神经干细胞移植治疗脑性瘫痪并重度视觉障碍患儿的疗效［J］.实用儿科临床杂志,2009,24(10):771-774.

［10］屈素清，栾佐，刘卫鹏，胡晓红，龚小军.人神经干细胞移植治疗重度新生儿一氧化碳中毒的初步探讨［J］.海军总医院学报,2008,21(3):142-144.

［11］《中华儿科杂志》编辑部. 小儿脑性瘫痪的定义、诊断条件及分型［J］.中华儿科杂志，2005，43（3）：262.

［12］Yasuhara T, Matsukawa N, Hara K, Yu G, Xu L, Maki M, et al. Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson′s disease［J］. J Neurosci, 2006, 26(48): 12497-12511.

［13］Imitola J, Park KI, Teng YD, Nisim S, Lachyankar M, Ourednik J, et al. Stem cells: cross-talk and developmental programs［J］. Philos Trans R Soc Lond B Biol Sci, 2004, 359(1445): 823-837.

［14］Madhavan L, Ourednik V, Ourednik J. Neural stem/progenitor cells initiate the formation of cellular networks that provide neuroprotection by growth factor-modulated antioxidant expression［J］. Stem Cell, 2008, 26(1): 254-265.

［15］Martino G, Pluchino S. The therapeutic potential of neural stem cells［J］. Nat Rev Neurosci, 2006, 7(5): 395-406.

［16］Kelly S, Bliss TM, Shah AK, Sun GH, Ma M, Foo WC, et al. Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex［J］. Proc Natl Acad Sci U S A, 2004, 101(32): 11839-11844.

［17］Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, et al. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis［J］.Nature, 2003, 422(6933): 688-694.

［18］Park DH, Eve DJ, Sanberg PR, Musso J 3rd,Bachstetter AD, Wolfson A, et al. Increased neuronal proliferation in the dentate gyrus of aged rats following neural stem cell implantation［J］.Stem Cells Dev, 2010,19(2): 175-180.

［19］Lu P, Jones LL, Snyder EY, Tuszynski MH. Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury［J］. Exp Neurol, 2003, 181(2): 115-129.

［20］Haastert K, Ying Z, Grothe C, Gómez-Pinilla F. The effects of FGF-2 gene therapy combined with voluntary exercise on axonal regeneration across peripheral nerve gaps［J］. Neurosci Lett, 2008, 443(3): 179-183.

［21］Voronin LL, Altinbaev RS, Bayazitov IT, Gasparini S, Kasyanov AV, Saviane C, et al. Postsynaptic depolarisation enhances transmitter release and causes the appearance of responses at "silent" synapses in rat hippocampus［J］. Neuroscience, 2004, 126(1): 45-59.

［22］Isaac JT. Postsynaptic silent synapses: evidence and mechanisms［J］. Neuropharmacology, 2003, 45(4): 450-460.

［23］Berardi N, Lodovichi C, Caleo M, Pizzorusso T, Maffei L. Role of neurotrophins in neural plasticity: what we learn from the visual cortex［J］. Restor Neurol Neurosci, 1999, 15(2-3): 125-136.

［24］Itami C, Mizuno K, Kohno T, Nakamura S. Brain-derived neurotrophic factor requirement for activity-dependent maturation of glutamatergic synapse in developing mouse somatosensory cortex［J］. Brain Res, 2000, 857(1-2): 141-150.

［25］Tongiorgi E. Activity-dependent expression of brain-derived neurotrophic factor in dendrites: facts and open questions［J］. Neurosci Res, 2008, 61(4): 335-346.

［26］Seledtsov VI, Kafanova MY, Rabinovich SS, Poveshchenko OV, Kashchenko EA, Fel′de MA, et al. Cell therapy of cerebral palsy［J］. Bull Exp Biol Med, 2005, 139(4): 499-503.

［27］Mehta T, Feroz A, Thakkar U, Vanikar A, Shah V, Trivedi H. Subarachnoid placement of stem cells in neurological disorders［J］. Transplant Proc, 2008, 40(4): 1145-1147.

［28］Madhavan L, Collier TJ. A synergistic approach for neural repair: cell transplantation and induction of endogenous precursor cell activity［J］. Neuropharmacology, 2010, 58(6): 835-844.