title: 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.
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.
authors.affiliation: Department of Biomedical Engineering, Yale University, Malone Engineering Center 311, New Haven, CT 06520, USA.
authors.forename: Millicent Ford
authors.initials: MF
authors.lastname: Rauch
authors.forename: Sara Royce
authors.initials: SR
authors.lastname: Hynes
authors.forename: James
authors.initials: J
authors.lastname: Bertram
authors.forename: Andy
authors.initials: A
authors.lastname: Redmond
authors.forename: Rebecca
authors.initials: R
authors.lastname: Robinson
authors.forename: Cicely
authors.initials: C
authors.lastname: Williams
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Madri
authors.forename: Erin B
authors.initials: EB
authors.lastname: Lavik
mesh_terms: D020341:Absorbable Implants / Q000592:standards / Q000639:trends*; D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000254:growth & development; D001812:Blood-Brain Barrier / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000637:transplantation*; D005260:Female; D006016:Glycolates / Q000627:therapeutic use; D020100:Hydrogels / Q000627:therapeutic use; D019344:Lactic Acid; D008833:Microcirculation / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013116:Spinal Cord / Q000098:blood supply / Q000166:cytology / Q000502:physiology; D013119:Spinal Cord Injuries / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000592:standards / Q000639:trends; D016896:Treatment Outcome
chemical_list: D006016:Glycolates; D020100:Hydrogels; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid