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CD133 阳性的周细胞与脊髓损伤中 SDF-1 和 CXCR4 的关系。

CD133 expressing pericytes and relationship to SDF-1 and CXCR4 in spinal cord injury.

机构信息

Spinal Injury Research, Swiss Paraplegic Research, Guido A. Zäch Strasse 4, 6207 Nottwil, Switzerland.

出版信息

Curr Neurovasc Res. 2010 May;7(2):144-54. doi: 10.2174/156720210791184907.

DOI:10.2174/156720210791184907
PMID:20374199
Abstract

Compression injury to the spinal cord (SC) results in vascular changes affecting the severity of the primary damage of the spinal cord. The recruitment of bone marrow (BM)-derived cells contribute to revascularization and tissue regeneration in a wide range of ischemic pathologies. Involvement of these cells in the vascular repair process has been investigated in an animal model of spinal cord injury (SCI). Temporal gene and protein expression of the BM-derived stem cell markers CD133 and CD34, of the mobilization factor SDF-1 and its receptor CXCR4 were determined following SC compression injury in rats. CD133 was expressed in uninjured tissue by cells surrounding arterioles identified as pericytes by co-expression of alpha-SMA. These cells mostly disappeared 2 days after injury but repopulated the tissue after 2 weeks. CD34 was expressed by endothelial cells and CD11b+ macrophages/microglia invading the injured tissue as observed 2 weeks following injury. SDF-1 was induced in reactive astrocytes and endothelial cells not until 2 weeks post-SCI. Comparison of the variation between CD34, CD133, CXCR4, and SDF-1 revealed a corresponding trend of CD133 with the SDF-1 expression. This study showed that resident microvascular CD133+ pericytes with presumptive stem cell potential are sensitive to SCI. Their decline following SCI and the delayed induction of SDF-1 may contribute to vessel destabilisation and inefficient revascularization. In addition, none of the analyzed markers could be assigned clearly to BM-derived cells. Together, our findings suggest that effective recruitment of pericytes may serve as a therapeutic option to improve microcirculation after SCI.

摘要

脊髓(SC)的压缩损伤导致血管变化,影响脊髓的原发性损伤的严重程度。骨髓(BM)来源的细胞的募集有助于在广泛的缺血性病理中实现再血管化和组织再生。这些细胞在脊髓损伤(SCI)的动物模型中参与血管修复过程。在大鼠 SCI 后,确定了 BM 源性干细胞标志物 CD133 和 CD34、动员因子 SDF-1 及其受体 CXCR4 的基因和蛋白表达的时间变化。CD133 在未受伤的组织中由围绕小动脉的细胞表达,这些细胞通过共表达α-SMA 被鉴定为周细胞。这些细胞在损伤后 2 天大部分消失,但在 2 周后重新填充组织。CD34 由内皮细胞和浸润损伤组织的 CD11b+巨噬细胞/小胶质细胞表达,如损伤后 2 周观察到的那样。SDF-1 仅在 SCI 后 2 周才在反应性星形胶质细胞和内皮细胞中诱导。CD34、CD133、CXCR4 和 SDF-1 之间的变化比较显示 CD133 与 SDF-1 表达具有相应的趋势。这项研究表明,具有假定干细胞潜能的常驻微血管 CD133+周细胞对 SCI 敏感。它们在 SCI 后减少和 SDF-1 的延迟诱导可能导致血管不稳定和低效的再血管化。此外,分析的标记物都不能明确地分配给 BM 来源的细胞。总之,我们的研究结果表明,有效的周细胞募集可能是改善 SCI 后微循环的一种治疗选择。

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