Role of Fibroblasts in Axon Regeneration after SCI

描述(申请人提供)：脊髓损伤(SCI)导致疤痕组织的形成，这是轴突再生的有力障碍。这种疤痕是由啮齿动物和人类体内细胞外基质(ECM)分子的过度沉积组成的。为什么大多数轴突不能生长到这个富含ECM的区域，这一点尚不完全清楚。体外检测表明成纤维细胞 作为抑制性细胞外基质分子的主要来源，但在体内是否也是如此尚不清楚。虽然脑膜被认为是脊髓损伤后成纤维细胞的主要来源，但最近的证据表明，血管周围的壁龛可能是瘢痕组织的替代来源。本研究的总体目标是确定血管周围成纤维细胞在脊髓挫伤后瘢痕形成中的作用，以促进脊髓挫伤后轴突再生：1)确定成纤维细胞在脊髓挫伤后的时空分布和细胞命运；2)确定成纤维细胞消融对脊髓挫伤后瘢痕形成和轴突再生的影响。3)检测成纤维细胞PDGFR-�在脊髓损伤后瘢痕形成和轴突再生中的作用。我们提出的研究将填补成纤维细胞在脊髓损伤动物模型中作用的知识空白，并可能揭示治疗脊髓损伤患者的新的治疗靶点。

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) results in formation of scar tissue that is a potent barrier to axon regeneration. This scar is comprised of excess deposition of extracellular matrix (ECM) molecules in both rodents and humans. Why most axons fail to grow into this ECM-rich region is not fully understood. In vitro assays have implicated fibroblasts as a major source of inhibitory ECM molecules, but whether this also true in vivo is not clear. While the meninges were thought to be the primary source of fibroblasts after SCI, recent evidence indicates that the perivascular niche could be an alternative source of the scar tissue. The overall goal of this proposal is to determine the role of perivascular fibroblasts in scar formation in order to promote axon regeneration after contusive SCI by pursuing the following aims: 1) Determine the temporospatial distribution and the cellular fate of fibroblasts after contusive SCI 2) Determine the effect of fibroblast ablation on scar formation and axon regeneration after SCI. 3) Determine the role of fibroblast PDGFR-� on scar formation and axon regeneration after SCI. Our proposed studies will fill a gap in knowledge about the role of fibroblasts in animal models of SCI and may reveal new therapeutic targets to treat SCI patients.