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胶质细胞和非神经细胞特性的比较研究,用于移植介导的损伤脊髓修复。

A comparative study of glial and non-neural cell properties for transplant-mediated repair of the injured spinal cord.

机构信息

Spinal Cord Group, Institute of Neuroscience & Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.

出版信息

Glia. 2013 Apr;61(4):513-28. doi: 10.1002/glia.22452. Epub 2013 Jan 16.

Abstract

Cell transplantation is one strategy for encouraging regeneration after spinal cord injury and a range of cell types have been investigated for their repair potential. However, variations in study design complicate determination of which cells are most effective. In this study we have carried out a direct comparison of the regenerative and integrative properties of several cell preparations following transplantation into the lesioned rat spinal cord. Transplants included: (i) purified olfactory ensheathing cells (OECs) and (ii) fibroblast-like cells, from olfactory bulb (OBFB-L), (iii) a 50:50 mixture of (i) and (ii) (OEC/OBFB-L), (iv) dissociated nasal mucosa (OM), (v) purified peripheral nerve Schwann cells (SCs), (vi) peripheral nerve fibroblasts, and (vii) skin fibroblasts (SF). All transplants supported axonal regeneration: OECs and SCs promoted the greatest regeneration while OBFB-like cells were least efficient and mixed cell populations were less effective than purified populations. Tract-tracing experiments demonstrated that none of the cell types promoted regeneration beyond the lesion. Although all cell types prevented cavity formation, the extent of astrocytic hypertrophy [GFAP immunoreactivity (IR) at the transplant/lesion site] differed markedly. OECs and SCs were associated with the least GFAP-IR, fibroblasts and fibroblast-like cells resulted in greater GFAP-IR while hypertrophy surrounding transplants of OM was most extensive. These differences in host-transplant reactivity were confirmed by transplanting cells into normal spinal cord where the cellular interaction is not complicated by injury. Thus, purified glial cells have advantages for transplant-mediated repair, combining maximal support for axonal regeneration with a minimal astrocytic reaction around the transplant site.

摘要

细胞移植是一种促进脊髓损伤后再生的策略,已经研究了多种细胞类型来评估其修复潜力。然而,研究设计的差异使得确定哪种细胞最有效变得复杂。在本研究中,我们在损伤的大鼠脊髓内移植后,直接比较了几种细胞制剂的再生和整合特性。移植包括:(i)纯化的嗅鞘细胞(OECs)和(ii)来自嗅球的成纤维样细胞(OBFB-L),(iii)(i)和(ii)的 50:50 混合物(OEC/OBFB-L),(iv)分离的鼻黏膜(OM),(v)纯化的外周神经施万细胞(SCs),(vi)外周神经成纤维细胞和(vii)皮肤成纤维细胞(SF)。所有移植均支持轴突再生:OECs 和SCs 促进了最大的再生,而 OBFB 样细胞效率最低,混合细胞群体的效果不如纯化群体。追踪实验表明,没有一种细胞类型能促进损伤部位以外的再生。尽管所有细胞类型都能防止空洞形成,但星形胶质细胞肥大的程度[移植/损伤部位的 GFAP 免疫反应(IR)]差异显著。OECs 和SCs 与最少的 GFAP-IR 相关,成纤维细胞和成纤维样细胞导致更多的 GFAP-IR,而 OM 移植周围的肥大最为广泛。将细胞移植到正常脊髓中,由于损伤的复杂性,细胞之间的相互作用不复杂,证实了这些宿主-移植反应的差异。因此,纯化的神经胶质细胞在移植介导的修复中具有优势,在最大程度地支持轴突再生的同时,在移植部位周围引起最小的星形胶质细胞反应。

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