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.
LIU Wei-Peng,QU Su-Qing,LUAN Zuo et al. Treatment of cerebral palsy with transplantation of human neural progenitor cells[J]. 中国当代儿科杂志, 2012, 14(10): 759-762.
LIU Wei-Peng,QU Su-Qing,LUAN Zuo et al. Treatment of cerebral palsy with transplantation of human neural progenitor cells[J]. CJCP, 2012, 14(10): 759-762.
[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.
[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.
[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.