Menezes Karla, Nascimento Marcos Assis, Gonçalves Juliana Pena, Cruz Aline Silva, Lopes Daiana Vieira, Curzio Bianca, Bonamino Martin, de Menezes João Ricardo Lacerda, Borojevic Radovan, Rossi Maria Isabel Doria, Coelho-Sampaio Tatiana
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
PLoS One. 2014 May 15;9(5):e96020. doi: 10.1371/journal.pone.0096020. eCollection 2014.
Cell therapy is a promising strategy to pursue the unmet need for treatment of spinal cord injury (SCI). Although several studies have shown that adult mesenchymal cells contribute to improve the outcomes of SCI, a description of the pro-regenerative events triggered by these cells is still lacking. Here we investigated the regenerative properties of human adipose tissue derived stromal cells (hADSCs) in a rat model of spinal cord compression. Cells were delivered directly into the spinal parenchyma immediately after injury. Human ADSCs promoted functional recovery, tissue preservation, and axonal regeneration. Analysis of the cord tissue showed an abundant deposition of laminin of human origin at the lesion site and spinal midline; the appearance of cell clusters composed of neural precursors in the areas of laminin deposition, and the appearance of blood vessels with separated basement membranes along the spinal axis. These effects were also observed after injection of hADSCs into non-injured spinal cord. Considering that laminin is a well-known inducer of axonal growth, as well a component of the extracellular matrix associated to neural progenitors, we propose that it can be the paracrine factor mediating the pro-regenerative effects of hADSCs in spinal cord injury.
细胞疗法是满足脊髓损伤(SCI)治疗未满足需求的一种有前景的策略。尽管多项研究表明成年间充质细胞有助于改善脊髓损伤的治疗效果,但仍缺乏对这些细胞引发的促再生事件的描述。在此,我们在大鼠脊髓压迫模型中研究了人脂肪组织来源的基质细胞(hADSCs)的再生特性。损伤后立即将细胞直接注入脊髓实质。人脂肪间充质干细胞促进了功能恢复、组织保存和轴突再生。对脊髓组织的分析显示,在损伤部位和脊髓中线有大量人源层粘连蛋白沉积;在层粘连蛋白沉积区域出现由神经前体细胞组成的细胞簇,以及沿脊髓轴出现具有分离基底膜的血管。将人脂肪间充质干细胞注入未损伤的脊髓后也观察到了这些效应。鉴于层粘连蛋白是一种众所周知的轴突生长诱导剂,也是与神经祖细胞相关的细胞外基质的组成部分,我们认为它可能是介导人脂肪间充质干细胞在脊髓损伤中促再生作用的旁分泌因子。