title: Adipose-derived endothelial and mesenchymal stem cells enhance vascular network formation on three-dimensional constructs in vitro.
abstract: BACKGROUND
  Adipose-derived mesenchymal stem cells (MSCs) have been gaining fame mainly due to their vast clinical potential, simple isolation methods and minimal donor site morbidity. Adipose-derived MSCs and microvascular endothelial cells have been shown to bear angiogenic and vasculogenic capabilities. We hypothesized that co-culture of human adipose-derived MSCs with human adipose-derived microvascular endothelial cells (HAMECs) will serve as an effective cell pair to induce angiogenesis and vessel-like network formation in three-dimensional scaffolds in vitro.
  
  
  METHODS
  HAMECs or human umbilical vein endothelial cells (HUVECs) were co-cultured on scaffolds with either MSCs or human neonatal dermal fibroblasts. Cells were immunofluorescently stained within the scaffolds at different time points post-seeding. Various analyses were performed to determine vessel length, complexity and degree of maturity.
  
  
  RESULTS
  The HAMEC:MSC combination yielded the most organized and complex vascular elements within scaffolds, and in the shortest period of time, when compared to the other tested cell combinations. These differences were manifested by higher network complexity, more tube alignment and higher α-smooth muscle actin expression. Moreover, these generated microvessels further matured and developed during the 14-day incubation period within the three-dimensional microenvironment.
  
  
  CONCLUSIONS
  These data demonstrate optimal vascular network formation upon co-culture of microvascular endothelial cells and adipose-derived MSCs in vitro and constitute a significant step in appreciation of the potential of microvascular endothelial cells and MSCs in different tissue engineering applications that can also be advantageous in in vivo studies.
authors.affiliation: Inter-departmental Program in Biotechnology, Technion-Israel Institute of Technology, Haifa, 32000, Israel. freiman.alina@gmail.com.|Biomedical Engineering Department, Technion-Israel Institute of Technology, Haifa, 32000, Israel. freiman.alina@gmail.com.
authors.forename: Alina
authors.initials: A
authors.lastname: Freiman
authors.affiliation: Biomedical Engineering Department, Technion-Israel Institute of Technology, Haifa, 32000, Israel. yuliash@tx.technion.ac.il.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Shandalov
authors.affiliation: Biomedical Engineering Department, Technion-Israel Institute of Technology, Haifa, 32000, Israel. dekeld@tx.technion.ac.il.
authors.forename: Dekel
authors.initials: D
authors.lastname: Rozenfeld
authors.affiliation: Biomedical Engineering Department, Technion-Israel Institute of Technology, Haifa, 32000, Israel. erez.shor@gmail.com.
authors.forename: Erez
authors.initials: E
authors.lastname: Shor
authors.affiliation: Biomedical Engineering Department, Technion-Israel Institute of Technology, Haifa, 32000, Israel. Sofifeldman3012@gmail.com.
authors.forename: Sofia
authors.initials: S
authors.lastname: Segal
authors.affiliation: Bonus BioGroup Ltd., Haifa, 3508501, Israel. drorbd@bonus-bio.com.
authors.forename: Dror
authors.initials: D
authors.lastname: Ben-David
authors.affiliation: Bonus BioGroup Ltd., Haifa, 3508501, Israel. shaime@bonus-bio.com.
authors.forename: Shai
authors.initials: S
authors.lastname: Meretzki
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaplan Hospital, Rehovot, Israel. danaeg@clalit.org.il.
authors.forename: Dana
authors.initials: D
authors.lastname: Egozi
authors.affiliation: Biomedical Engineering Department, Technion-Israel Institute of Technology, Haifa, 32000, Israel. Shulamit@bm.technion.ac.il.
authors.forename: Shulamit
authors.initials: S
authors.lastname: Levenberg
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003470:Culture Media / Q000737:chemistry; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D018919:Neovascularization, Physiologic; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D003470:Culture Media; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)