title: VEGF optimizes the formation of tissue-engineered small intestine.
abstract: OBJECTIVE
  To determine the effect of VEGF overexpression on tissue-engineered small intestine (TESI) formation.
  
  
  METHODS
  Organoid units were isolated from the intestines of 2-week-old transgenic mouse pups capable of inducible, ubiquitous VEGF overexpression (CMV-Cre/rtTA/tet(0)-VEGF) and implanted into nonobese diabetic/severe combined immunodeficiency mice. Resulting TESI were explanted at 2 and 4 weeks, and studied by histology, tissue ELISA and immunofluorescence.
  
  
  RESULTS
  At 2 weeks postimplantation, the TESI mucosa from the VEGF overexpression group formed rudimentary villi and more crypts compared with controls, which demonstrated a flat epithelium with few crypts and no villi. At 4 weeks postimplantation, the TESI from the VEGF overexpression group was larger and significantly heavier than controls. Within the mucosa, the villus height and crypt depth was significantly longer, contained a greater percentage of proliferating crypt epithelial cells and consisted of all four terminally differentiated epithelial cell types. There was also a significant increase in the capillary density within the submucosa.
  
  
  CONCLUSIONS
  Overexpression of VEGF optimizes the formation of TESI by increasing the submucosal capillary density, crypt epithelial proliferation and the rate of mucosa formation. A larger construct with increased villus and crypt height was noted after 4 weeks in vivo.
authors.affiliation: Developmental Biology and Regenerative Medicine Program, Saban Research Institute, Children's Hospital Los Angeles, 4650 W Sunset Blvd, MS#100, Los Angeles, CA 90027, USA.
authors.forename: Jamil A
authors.initials: JA
authors.lastname: Matthews
authors.forename: Frédéric G
authors.initials: FG
authors.lastname: Sala
authors.forename: Allison L
authors.initials: AL
authors.lastname: Speer
authors.forename: David
authors.initials: D
authors.lastname: Warburton
authors.forename: Tracy C
authors.initials: TC
authors.lastname: Grikscheit
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D007413:Intestinal Mucosa / Q000378:metabolism / Q000648:ultrastructure; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D051379:Mice; D008822:Mice, Transgenic; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A