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人胚胎脊髓实体异种移植于急性和慢性脊髓空洞:一项形态学与功能研究

Solid human embryonic spinal cord xenografts in acute and chronic spinal cord cavities: a morphological and functional study.

作者信息

Akesson E, Holmberg L, Jönhagen M E, Kjaeldgaard A, Falci S, Sundström E, Seiger A

机构信息

Department of NEUROTEC, Karolinska Institutet, Huddinge University Hospital, S-141 86, Sweden.

出版信息

Exp Neurol. 2001 Aug;170(2):305-16. doi: 10.1006/exnr.2001.7707.

Abstract

While therapeutic spinal cord grafting procedures are of interest in the chronic spinal cord injury stage, previous experimental grafting studies, including human spinal cord tissue, have mainly focused on the acute stage. Therefore, solid human embryonic spinal cord grafts were implanted in acute or chronic spinal cord aspiration cavities of immunodeficient rats to compare the morphological and locomotor outcome to that of lesion alone cases. Locomotor function was assessed using the Basso, Beattie, and Bresnahan open-field locomotor rating scale up to 6 months, while the morphological evaluation of graft survival, growth, and integration was performed at 6 weeks or 6 months after implantation. Graft survival was 94% in both lesion models, while graft growth was enhanced in the chronic compared to the acute cavity group. Human specific Thy-1 and neurofilament immunoreactive fibers were observed up to 7 mm into host white matter, while aminergic fibers were observed up to 1 mm into the grafts. Abundant calcitonin gene-related peptide immunoreactive fibers in the grafts in the absence both of immunoreactive cell bodies and colocalized human-specific neurofilament immunoreactivity, suggested host fiber ingrowth. At 6 months, the grafted cases presented less central canal deformation and lower glial fibrillary acidic protein immunoreactivity at the host cavity border compared to that of the nongrafted cases. The strong compensatory regain of locomotor function after unilateral spinal cord lesions was not affected by the human spinal cord grafts. In conclusion, solid human embryonic spinal cord tissue transplanted to a cavity in the adult injured spinal cord results in beneficial morphological effects in both the acute and chronic spinal cord lesion.

摘要

虽然治疗性脊髓移植手术在慢性脊髓损伤阶段备受关注,但以往包括人类脊髓组织在内的实验性移植研究主要集中在急性期。因此,将实体人类胚胎脊髓移植到免疫缺陷大鼠的急性或慢性脊髓抽吸腔中,以比较其与单纯损伤病例在形态学和运动功能方面的结果。使用Basso、Beattie和Bresnahan旷场运动评分量表评估长达6个月的运动功能,同时在植入后6周或6个月对移植的存活、生长和整合进行形态学评估。在两种损伤模型中移植存活率均为94%,与急性腔组相比,慢性腔组的移植生长得到增强。在宿主白质中观察到人类特异性Thy-1和神经丝免疫反应性纤维深入达7毫米,而在移植组织中观察到胺能纤维深入达1毫米。移植组织中大量降钙素基因相关肽免疫反应性纤维,既没有免疫反应性细胞体,也没有共定位的人类特异性神经丝免疫反应性,提示有宿主纤维长入。在6个月时,与未移植病例相比,移植病例在宿主腔边界处中央管变形较小,胶质纤维酸性蛋白免疫反应性较低。单侧脊髓损伤后运动功能的强烈代偿性恢复不受人类脊髓移植的影响。总之,将实体人类胚胎脊髓组织移植到成年受损脊髓的腔中,在急性和慢性脊髓损伤中均产生有益的形态学效应。

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