Long-term in vivo imaging of human angiogenesis: critical role of bone marrow-derived mesenchymal stem cells for the generation of durable blood vessels.
Angiogenesis is a multistep process that encompasses complex molecular and cellular interactions that can not be recapitulated in vitro. Here, we demonstrate that vasculature generated from lentivirally transduced human primary endothelial cells expressing firefly luciferase and co-implanted with human bone marrow mesenchymal stem cells in immunodeficient mice can be assessed quantitatively by in vivo whole body bioluminescence imaging for more than 120 days. Luciferase activity correlated with the formation of a network of functional, mature blood vessels of human nature inside the implant that critically depend on the presence of mesenchymal stem cells. In summary, our study offers an unprecedented opportunity to perform long-term serial analysis of the molecular events involved in the angiogenic process and monitoring responses to anti-angiogenic agents.
Sanz
Laura
L
Unidad de Inmunología Molecular, Hospital Universitario Puerta de Hierro, 28035 Madrid, Spain.
Santos-Valle
Patricia
P
Alonso-Camino
Vanesa
V
Salas
Clara
C
Serrano
Antonio
A
Vicario
José Luís
JL
Cuesta
Angel M
AM
Compte
Marta
M
Sánchez-Martín
David
D
Alvarez-Vallina
Luís
L
D034861:Abdominal Wall / Q000098:blood supply; D000368:Aged; D000818:Animals; D001808:Blood Vessels / Q000166:cytology* / Q000254:growth & development; D001854:Bone Marrow Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D005260:Female; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology*; D014161:Transduction, Genetic / Q000379:methods; D014471:Umbilical Veins / Q000166:cytology
D008156:Luciferases