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.
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.
Rauch
Millicent Ford
MF
Department of Biomedical Engineering, Yale University, Malone Engineering Center 311, New Haven, CT 06520, USA.
Hynes
Sara Royce
SR
Bertram
James
J
Redmond
Andy
A
Robinson
Rebecca
R
Williams
Cicely
C
Xu
Hao
H
Madri
Joseph A
JA
Lavik
Erin B
EB
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
D006016:Glycolates; D020100:Hydrogels; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid