Engineering angiogenesis following spinal cord injury: a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood-spinal cord barrier.
Engineering angiogenesis following spinal cord injury: a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood-spinal cord barrier.
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DOI：
10.1111/j.1460-9568.2008.06567.x
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Lavik EB
中科院分区：
文献类型：
--
作者：
Rauch MF;Hynes SR;Bertram J;Redmond A;Robinson R;Williams C;Xu H;Madri JA;Lavik EB
血管生成先于脊髓损伤（SCI）后的恢复，其程度与神经再生相关，表明血管生成可能在修复中发挥作用。研究血管生成作用的一个重要前提是能够以可控的方式诱导血管生成。以前，我们发现，内皮细胞（EC）和神经祖细胞（NPC）的共培养促进了稳定的管在体外和稳定的，功能性的血管网络在体内皮下模型的形成。我们试图测试类似的共培养是否会导致损伤后脊髓中稳定的功能性血管的形成。我们在可生物降解的双组分植入物系统中创建了微血管网络，并在脊髓损伤的大鼠半切模型中测试了共培养物或对照（病变对照、单独植入物、植入物加EC或植入物加NPC）促进血管生成的能力。与病变对照组、单独植入物组或植入物+NPC组相比，共培养植入物导致功能性血管增加4倍，与植入物+EC组相比，功能性血管增加2倍。此外，共培养植入物中一半的血管显示内皮屏障抗原阳性染色，内皮屏障抗原是血脊髓屏障（BSB）形成的标志物。其他组在损伤中心均未显示BSB阳性染色。本研究为SCI后诱导血管新生提供了一种新的方法，为进一步研究其在损伤修复中的作用奠定了基础。
Angiogenesis precedes recovery following spinal cord injury (SCI), and its extent correlates with neural regeneration suggesting that angiogenesis may play a role in repair. An important precondition for studying the role of angiogenesis is the ability to induce it in a controlled manner. Previously, we showed that a coculture of endothelial cells (ECs) and neural progenitor cells (NPCs) promoted the formation of stable tubes in vitro and stable, functional vascular networks in vivo in a subcutaneous model. We sought to test whether a similar coculture would lead to formation of stable functional vessels in the spinal cord following injury. We created microvascular networks in a biodegradable two component implant system and tested the ability of the coculture or controls (lesion control, implant alone, implant plus ECs, or implant plus NPCs) to promote angiogenesis in a rat hemisection model of spinal cord injury. The coculture implant led to a four fold increase in functional vessels compared to the lesion control, implant alone, or implant plus NPCs groups and a 2 fold increase in functional vessels over the implant plus ECs group. Furthermore, half of the vessels in the coculture implant exhibited positive staining for the endothelial barrier antigen, a marker for formation of the blood spinal cord barrier (BSB). No other groups showed positive staining for the BSB in the injury epicenter. This work provides a novel method to induce angiogenesis following SCI and a foundation for studying its role in repair.
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影响因子：
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