title: Additive effect of mesenchymal stem cells and VEGF to vascularization of PLGA scaffolds.
abstract: Bone marrow derived mesenchymal stem cells (bmMSCs) are widely used for the generation of tissue engineering constructs, since they can differentiate into different cell types occurring in bone tissues. Until now their use for the generation of tissue engineering constructs is limited. All cells inside a tissue engineering construct die within a short period of time after implantation of the construct because vascularization and establishment of connections to the recipient circulatory system is a time consuming process. We therefore compared the influences of bmMSC, VEGF and a combination of both on the early processes of vascularization, utilizing the mice skinfold chamber model and intravital fluorescence microscopy. Tissue engineering constructs based on collagen coated Poly d,l-lactide-co-glycolide (PLGA) scaffolds, were either functionalized by coating with vascular endothelial growth factor (VEGF) or vitalized with bmMSC. PLGA without cells and growth factor was used as the control group. Functionalized and vitalized tissue engineering constructs showed an accelerated growth of microvessels compared to controls. Only marginal differences in vascular growth were detected between VEGF containing and bmMSC containing constructs. Constructs containing VEGF and bmMSC showed a further enhanced microvascular growth at day 14. We conclude that bmMSCs are well suited for bone tissue engineering applications, since they are a valuable source of angiogenic growth factors and are able to differentiate into the tissue specific cell types of interest. The dynamic process of vascularization triggered by growth factor producing cells can be amplified and stabilized with the addition of accessory growth factors, leading to a persisting angiogenesis, but strategies are needed that enhance the resistance of bmMSC to hypoxia and increase survival of these cells until the tissue engineering construct has build up a functional vascular system.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Electronic address: Kampmann.Andreas@mh-hannover.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kampmann
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindhorst
authors.forename: Paul
authors.initials: P
authors.lastname: Schumann
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Zimmerer
authors.forename: Horst
authors.initials: H
authors.lastname: Kokemüller
authors.forename: Martin
authors.initials: M
authors.lastname: Rücker
authors.forename: Nils-Claudius
authors.initials: NC
authors.lastname: Gellrich
authors.forename: Frank
authors.initials: F
authors.lastname: Tavassol
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001783:Blood Flow Velocity; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D036904:Leukocyte Rolling / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*; D012995:Solubility; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D043925:Angiogenesis Inducing Agents; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid