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评估轴突向含有基质胶中经血管内皮生长因子转染的干细胞的胶原神经导管内生长的情况。

Assessment of axonal growth into collagen nerve guides containing VEGF-transfected stem cells in matrigel.

作者信息

Kempton Laurence B, Gonzalez Mark H, Leven Robert M, Hughes W Frank, Beddow Sara, Santhiraj Yaveen, Archibald Simon J, El Hassan Bassem, Shott Susan, Kerns James M

机构信息

Department of Anatomy and Cell Biology, Rush University Medical Center, 600 S Paulina Ave., Chicago, IL 60612, USA.

出版信息

Anat Rec (Hoboken). 2009 Feb;292(2):214-24. doi: 10.1002/ar.20844.

DOI:10.1002/ar.20844
PMID:19089906
Abstract

The early events associated with axonal growth into 10-mm nerve gaps were studied histologically in the rat sciatic nerve model to determine if the outgrowth of blood vessels, Schwann cells, and axons could be enhanced. In the first two experimental groups, collagen nerve guides were filled with either saline or Matrigel. Marrow-derived mesenchymal stem cells (MSCs) were added to Matrigel in two other groups, one of which contained cells transfected with VEGF (MSC/VEGF). After 21 days, the injury site was exposed, fixed, sectioned, and volume fractions of the conduit contents were determined by point counting. The bioresorbable collagen conduits appropriately guided the axons and vessels in a longitudinal direction. The volume fraction of axons was significantly greater in the group with saline when compared with all three groups with Matrigel. This measure had a significant positive correlation with actual counts of myelinated axons. The blood vessel volume fraction in the Matrigel group decreased compared with the saline group, but was restored in the MSC/VEGF group. All Matrigel groups had comparable cellularity and showed a distribution of residual Matrigel in acellular zones. The saline group, by contrast, sustained a network of delicate fibroblastic processes that compartmentalized the nerve and its natural matrix as it became infiltrated by axons as minifascicles. In conclusion, the reduction of axonal outgrowth in the Matrigel groups, when compared with the saline group, suggests that Matrigel may impede the early regenerative process even when enriched by the addition of MSCs or VEGF-transfected cells.

摘要

在大鼠坐骨神经模型中,通过组织学方法研究了与轴突长入10毫米神经间隙相关的早期事件,以确定血管、施万细胞和轴突的生长是否可以增强。在前两个实验组中,胶原神经导管分别填充生理盐水或基质胶。在另外两组中,将骨髓间充质干细胞(MSC)添加到基质胶中,其中一组包含用血管内皮生长因子(VEGF)转染的细胞(MSC/VEGF)。21天后,暴露损伤部位,固定、切片,通过点计数法确定导管内容物的体积分数。可生物吸收的胶原导管能在纵向上适当引导轴突和血管。与所有含基质胶的三组相比,生理盐水组的轴突体积分数显著更高。该测量值与有髓轴突的实际计数有显著正相关。与生理盐水组相比,基质胶组的血管体积分数降低,但在MSC/VEGF组中得以恢复。所有基质胶组的细胞密度相当,且在无细胞区显示有残留基质胶的分布。相比之下,生理盐水组维持着一个由纤细的成纤维细胞突起构成的网络,当轴突以小束状形式侵入时,该网络将神经及其天然基质分隔开来。总之,与生理盐水组相比,基质胶组轴突生长减少,这表明即使添加了MSC或VEGF转染细胞,基质胶仍可能阻碍早期再生过程。

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