Authors: Rauch, Millicent Ford¹; Hynes, Sara Royce¹; Bertram, James¹; Redmond, Andy²; Robinson, Rebecca¹; Williams, Cicely³; Xu, Hao¹; Madri, Joseph A.⁴; Lavik, Erin B.¹

Source: European Journal of Neuroscience, Volume 29, Number 1, January 2009 , pp. 132-145(14)

Publisher: Wiley-Blackwell

Abstract:

Angiogenesis precedes recovery following spinal cord injury 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 the 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 + ECs or implant + NPCs) to promote angiogenesis in a rat hemisection model of spinal cord injury. The coculture implant led to a fourfold increase in functional vessels compared with the lesion control, implant alone or implant + NPCs groups and a twofold increase in functional vessels over the implant + ECs group. Furthermore, half of the vessels in the coculture implant exhibited positive staining for the endothelial barrier antigen, a marker for the formation of the blood-spinal cord barrier. No other groups have shown positive staining for the blood-spinal cord barrier in the injury epicenter. This work provides a novel method to induce angiogenesis following spinal cord injury and a foundation for studying its role in repair.

Keywords: blood-spinal cord barrier; hydrogel; microvasculature; poly(lactic-co-glycolic acid); rat; scaffold

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1460-9568.2008.06567.x

Affiliations: 1: Department of Biomedical Engineering, Yale University, 55 Prospect Street, Malone Engineering Center 311, New Haven, CT 06520, USA 2: Department of Neurosurgery, Yale University, New Haven, CT, USA 3: Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA 4: Department of Pathology, Yale University, New Haven, CT, USA

Publication date: 2009-01-01

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