中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (11): 1895-1904.doi: 10.4103/1673-5374.219052

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

球状基底细胞移植治疗脊髓损伤

  

  • 收稿日期:2017-09-26 出版日期:2017-11-15 发布日期:2017-11-15
  • 基金资助:

    印度政府生物科技部项目

Globose basal cells for spinal cord regeneration

Durai Murugan Muniswami1, Indirani Kanakasabapathy2, George Tharion1   

  1. 1 Department of Physical Medicine & Rehabilitation, Christian Medical College, Vellore, Tamil Nadu, India
    2 Department of Anatomy, Christian Medical College, Vellore, Tamil Nadu, India
  • Received:2017-09-26 Online:2017-11-15 Published:2017-11-15
  • Contact: Durai Murugan Muniswami,Ph.D.,durai.morgan@gmail.com.
  • Supported by:

    This study was financially supported by Department of Biotechnology, Ministry of Science & Technology, Government of India.

摘要:

嗅觉上皮是一种神经源性组织,在这一组织中干细胞/祖细胞群诱导的神经发生存续于整个成年期间。嗅神经上皮干/祖细胞的易获得性使其用于脊髓损伤细胞移植治疗的前景十分广阔。实验应用重物下坠打击法建立T10段脊髓损伤大鼠模型,在损伤后第9天,将5×105个从大鼠自体嗅上皮分离出的球状基底细胞(GBC)移植至其损伤脊髓中。以BBB评分、运动诱发电位和组织学研究评估发现,球状基底细胞移植促进脊髓损伤大鼠后肢运动功能恢复,腓肠肌EMG波幅增加,GFP标记的球状基底细胞在损伤中心周围存活并分化成βIII微管蛋白免疫阳性神经元样细胞。说明球状基底细胞可作为细胞移植治疗脊髓损伤的较为理想细胞来源。

orcid:0000-0001-6838-9727(Durai Murugan Muniswami)

关键词: 神经再生, 肌电图, 球状基底细胞, BBB评分, 脊髓损伤, 细胞移植

Abstract:

Spinal cord injury (SCI) is a devastating condition with loss of motor and sensory functions below the injury level. Cell based therapies are experimented in pre-clinical studies around the world. Neural stem cells are located intra-cranially in subventricular zone and hippocampus which are highly invasive sources.The olfactory epithelium is a neurogenic tissue where neurogenesis takes place throughout the adult life by a population of stem/progenitor cells. Easily accessible olfactory neuroepithelial stem/progenitor cells are an attractive cell source for transplantation in SCI. Globose basal cells (GBCs) were isolated from rat olfactory epithelium, characterized by flow cytometry and immunohistochemically. These cells were further studied for neurosphere formation and neuronal induction. T10 laminectomy was done to create drop-weight SCI in rats. On the 9th day following SCI, 5 × 105 cells were transplanted into injured rat spinal cord. The outcome of transplantation was assessed by the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, motor evoked potential and histological observation. GBCs expressed neural stem cell markers nestin, SOX2, NCAM and also mesenchymal stem cell markers (CD29, CD54, CD90, CD73, CD105). These cells formed neurosphere, a culture characteristics of NSCs and on induction, differentiated cells expressed neuronal markers βIII tubulin, microtubule-associated protein 2, neuronal nuclei, and neurofilament. GBCs transplanted rats exhibited hindlimb motor recovery as confirmed by BBB score and gastrocnemius muscle electromyography amplitude was increased compared to controls. Green fluorescent protein labelled GBCs survived around the injury epicenter and differentiated into βIII tubulin-immunoreactive neuron-like cells.GBCs could be an alternative to NSCs from an accessible source for autologous neurotransplantation after SCI without ethical issues.

Key words: nerve regeneration, the Basso, Beattie and Bresnahan (BBB) locomotor scale score, BBB score, EMG, globose basal cells, spinal cord injury, transplantation, neural stem cell marker, neural regeneration