Transplantation of neural stem cells by injection into traumatic lesions in the cerebral cortex

( views:155, downloads:0 )
LI Gang(Department of Neurosurgery, Guangdong Institute of Neurosurgery,Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China)
XU Ru-xiang(Department of Neurosurgery, Guangdong Institute of Neurosurgery,Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China)
KE Yi-quan(Department of Neurosurgery, Guangdong Institute of Neurosurgery,Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China)
JIANC Xiao-dan(Department of Neurosurgery, Guangdong Institute of Neurosurgery,Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China)
Journal Title:
Volume 7, Issue 02, 2008
Key Word:
Bone marrow stromal cells;Neural stem cells;Craniocerebral trauma;Cell transplantation

Abstract: Objective To determine whether autologous bone marrow strom ceils-derived neural stem cells(BMSCs-d-NSCs)can survive and grow after transplantated into traumatic lesions in monkey cerebral cortex.Methods Stromal cells from bone marrow were separated,adjusted to 1×106 cells/mL and seeded onto multi-well plates.We added medium,fetal calf serunl,leukemia inhibitory factor and basic fibroblast growth factor before incubating at 37℃ and 5% CO2 in a humidified atmosphere.Adherent cells were cultured in neural stem cell medium with FCS and retinoic acid and then characterized by nestin staining.BMSCs-d-NSCs were cultured with BrdU for 7 d and BrdU-stained cells were collected and resuspended.Traumatic lesions were made by Allen's method in the cerebral cortex of monkeys(Macaca fascicularis).Animals were assigned to immediate transplantation(IT)group(NSCs marked by BrdU staining were injected into the traumatic lesion immediately,n=3) or delayed transplantation (DT) group (BrdU marked NSCs were injected into the traumatic lesion at day 30 after injury,n=3).One animal was enrolled in the control group:traumatic lesions were made on each side of the monkey brain and the left side was injected with 0.5 mL NSCs culture medium without NSCs but containing the same concentration of BrdU,the right side was injected with NSCs marked by BrdU staining.Two animals in both IT and DT groups were sacrificed at each of the following post-transplantation times (1,3 or 6 months) and tissue sections from the transplantation area were stained;two animals in control group were sacrificed 6 month after transplantation.Results In both IT and DT groups,brown,BrdU-positive cells were observed in the lesions.There were no BrdU+ cells in the control group.Over the 6 months,transplanted cells first distributed as clusters and later as scattered.Cell morphology varied and cells had protuberances.After 6 months,BrdU positive cells were observed in white matter nearby the transplantation area.Conclusion BMSCs-d-NSCs can survive in brain,and migrate within injury sites.

  • [1]李钢,柯以铨,姜晓丹,等.食蟹猴骨髓基质干细胞体外诱导分化的实验研究[J].解放军医学杂志,2002,27(1 1):956-958.
  • [2]Cho T,Bae JH,Choi HB,et al.Human neural stem cells:electrophysiological properties of voltage-gated ion channels[J].Neuroreport,2002,13(1 1):1447-1452.
  • [3]Allen GV,Gerami D,Esser MJ.Conditioning effects of repetitive mild neurotrauma on motor function in an animal model of focal brain injury[J].Neuroscience,2000,99(1):93-105.
  • [4]Philippe T.Autologous transplantation in the central nervous system[J].Indian J Med Res,2006,124(6):613-618.
  • [5]Tropepe V,Sibilia M,Ciruna BG,et al.Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon[J].Dev Biol,1999,208(1):166-188.
  • [6]Mezey E,Chandross KJ,Harta G,et al.Turning blood into brain cells bearing neuronal antigens generated in vivo from bone marrow[J].Science,2000,290(5497):1779.
  • [7]姜晓丹,徐如祥,张世忠,等.胚鼠室管膜及成鼠骨髓神经干细胞分离培养及分化鉴定实验研究[J].中国临床神经科学杂志,2002,10(2):126-130.
  • [8]柯以铨,李钢,徐如祥,等.猕猴的开颅手术方法[J].中国比较医学杂志,2003,13(5):315-317.
  • [9]Asim M,Dunyue L,Lei W,et al.Treatment of traumatic brain injury in female rats with intravenous administration of bone marrow stromal cells[J].Neurosurgery,2001,49(5):1 196-1204.
  • [10]Veizovic T,Beech JS,Stroemer RP,et al.Resolution of stroke deficits following contralateral grafts of conditionally immortal neuroepithelial stem cells[J].Stroke,2001,32:1012-1019.
  • [11]Menet V,Gimenezy RM,Chauvet N,et al.Inactivation of the glial fibrillary acidic protein gene,but not that of vimentin,improves neuronal survival and neurite growth by modifying adhesion molecule wxpression[J].J Neurosci,2001,21:6147-6158.
  • [12]Li T,Zheng J,Xie Y,et al.Transplantable neural progenitor populations derived from rhesus monkey embryonic stem cell[J].Stem Cells,2005,23(9):1295-1303.
  • [13]Hamasaki T,Tanaka N,Ishida O,et al.Characterization of labeled neural progenitor cells for magnetic targeting[J].Neuroreport,2005,16(15):1641-1645.
  • [14]Parr AM,Tator CH.Intrathecal epidermal growth factor and fibroblast growth factor-2 exacerbate meningeal proliferative lesions associated with intrathecal catheters[J].Neurosurgery,2007,60(5):926-933.
  • [15]Shindo T,Matsumoto Y,Wang Q,et al.Differences in the neuronal stem cells survival,neuronal differentiation and neurological improvement after transplantation of neural stem cells between mild and severe experimental traumatic brain injury[J].J Med Invest,2006,53(1-2):42-51.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615