Group of Neuroplasticity and Regeneration, Institute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain.
PLoS One. 2013 Oct 11;8(10):e76141. doi: 10.1371/journal.pone.0076141. eCollection 2013.
Transplantation of bone marrow derived mesenchymal stromal cells (MSC) or olfactory ensheathing cells (OEC) have demonstrated beneficial effects after spinal cord injury (SCI), providing tissue protection and improving the functional recovery. However, the changes induced by these cells after their transplantation into the injured spinal cord remain largely unknown. We analyzed the changes in the spinal cord transcriptome after a contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. The gene profiles were analyzed by clustering and functional enrichment analysis based on the Gene Ontology database. We found that both MSC and OEC transplanted acutely after injury induce an early up-regulation of genes related to tissue protection and regeneration. In contrast, cells transplanted at 7 days after injury down-regulate genes related to tissue regeneration. The most important change after MSC or OEC transplant was a marked increase in expression of genes associated with foreign body response and adaptive immune response. These data suggest a regulatory effect of MSC and OEC transplantation after SCI regarding tissue repair processes, but a fast rejection response to the grafted cells. Our results provide an initial step to determine the mechanisms of action and to optimize cell therapy for SCI.
骨髓间充质基质细胞（MSC）或嗅鞘细胞（OEC）移植在脊髓损伤（SCI）后显示出有益的效果，提供组织保护并改善功能恢复。然而，这些细胞在移植到损伤的脊髓后引起的变化在很大程度上仍然未知。我们分析了挫伤损伤后和 MSC 或 OEC 移植后脊髓转录组的变化。细胞在损伤后立即或 7 天注射。在细胞移植后 2 天和 7 天，提取受伤脊髓段的 mRNA 并通过微阵列进行分析。基于基因本体数据库，通过聚类和功能富集分析对基因图谱进行分析。我们发现，损伤后急性移植的 MSC 和 OEC 均诱导与组织保护和再生相关的基因的早期上调。相比之下，在损伤后 7 天移植的细胞下调与组织再生相关的基因。MSC 或 OEC 移植后最重要的变化是与异物反应和适应性免疫反应相关的基因表达显著增加。这些数据表明 MSC 和 OEC 移植后对 SCI 组织修复过程具有调节作用，但对移植物细胞有快速排斥反应。我们的研究结果为确定作用机制和优化 SCI 细胞治疗提供了初步步骤。
