title: Vascularized bone transplant chimerism mediated by vascular endothelial growth factor.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) induces angiogenesis and osteogenesis in bone allotransplants. We aim to determine whether bone remodeling in VEGF-treated bone allotransplants results from repopulation with circulation-derived autogenous cells or survival of allogenic transplant-derived cells.
  
  
  METHODS
  Vascularized femoral bone transplants were transplanted from female Dark Agouti rats (DA;RT1(a) ) to male Piebald Viral Glaxo (PVG;RT1(c) ). Arteriovenous bundle implantation and short-term immunosuppression were used to maintain cellular viability. VEGF was encapsulated in biodegradable microspheres and delivered intramedullary in the experimental group (n = 22). In the control group (n = 22), no VEGF was delivered. Rats were sacrificed at 4 or 18 weeks. Laser capture microdissection of bone remodeling areas was performed at the inner and outer cortex. Sex-mismatched genes were quantified with reverse transcription-polymerase chain reaction to determine the amount of male cells to total cells, defined as the relative expression ratio (rER).
  
  
  RESULTS
  At 4 weeks, rER was significantly higher at the inner cortex in VEGF-treated transplants as compared to untreated transplants (0.622 ± 0.225 vs. 0.362 ± 0.081, P = 0.043). At 4 weeks, the outer cortex in the control group had a significantly higher rER (P = 0.038), whereas in the VEGF group, the inner cortex had a higher rER (P = 0.015). Over time, in the outer cortex the rER significantly increased to 0.634 ± 0.106 at 18 weeks in VEGF-treated rats (P = 0.049). At 18 weeks, the rER was >0.5 at all cortical areas in both groups.
  
  
  CONCLUSIONS
  These in vivo findings suggest a chemotactic effect of intramedullary applied VEGF on recipient-derived bone and could imply that more rapid angiogenesis of vascularized allotransplants can be established with microencapsulated VEGF.
authors: Department of Orthopedic Surgery, Microvascular Research Laboratory, Mayo Clinic, Rochester, MN.
authors: Wouter F
authors: WF
authors: Willems
authors: Mikko
authors: M
authors: Larsen
authors: Patricia F
authors: PF
authors: Friedrich
authors: Allen T
authors: AT
authors: Bishop
mesh_terms: D000818:Animals; D016025:Bone Transplantation / Q000379:methods*; D001842:Bone and Bones / Q000098:blood supply*; D002214:Capsules; D005260:Female; D008297:Male; D008866:Microsurgery; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D018183:Transplantation Chimera / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000502:physiology*
chemical_list: D002214:Capsules; D042461:Vascular Endothelial Growth Factor A