title: Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: a combined gene therapy-cell transplantation approach.
abstract: One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue-engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors, and optimal factor doses. This study reports an approach as a step forward to resolving this dilemma by combining an ex vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated by using 3D poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose-derived stromal cells (ADSCs) with adenovirus encoding the cDNA of VEGF. We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We thereby delineate the potential of ADSCs to promote vascular growth into biomaterials.
authors.affiliation: Departments of Orthopaedic Surgery and Chemical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Jabbarzadeh
authors.forename: Trevor
authors.initials: T
authors.lastname: Starnes
authors.forename: Yusuf M
authors.initials: YM
authors.lastname: Khan
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Wirtel
authors.forename: Meng
authors.initials: M
authors.lastname: Deng
authors.forename: Qing
authors.initials: Q
authors.lastname: Lv
authors.forename: Lakshmi S
authors.initials: LS
authors.lastname: Nair
authors.forename: Steven B
authors.initials: SB
authors.lastname: Doty
authors.forename: Cato T
authors.initials: CT
authors.lastname: Laurencin
mesh_terms: D000256:Adenoviridae; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D000273:Adipose Tissue / Q000378:metabolism / Q000648:ultrastructure; D001861:Bone Regeneration / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000235:genetics; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism* / Q000648:ultrastructure; D017154:Stromal Cells / Q000378:metabolism / Q000648:ultrastructure; D023822:Tissue Engineering / Q000379:methods; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid