Multipotent Adult Progenitor Cells (MAPC) contribute to hepatocarcinoma neovasculature
Miguel Barajas (a,b), Federico Franchi (a), Carlos Clavel (b), Xabier L. Aranguren (b), M. Gabriela Kramer (a), Gloria Abizanda (a), Juana Merino (c), Cristina Moreno (c), Leire Gárate (b), Anunciata Guitart (a), Iñigo Narvaiza (a), María Gutiérrez-Perez (b), Jose-Ignacio Riezu-Boj (a), Carmen Berasain (a), Jesús Prieto (a) and Felipe Prósper (b)
(a) Department of Medicine and Division of Hepatology and Gene Therapy, Clínica Universitaria/School of Medicine and Centre for Applied Medical Research (CIMA), University of Navarra, Spain
(b) Area of Hematology and Cell Therapy, Clínica Universitaria/School of Medicine and Centre for Applied Medical Research (CIMA), University of Navarra, Spain (c) Department of Immunology, Clínica Universitaria/School of Medicine, University of Navarra, Spain
The use of stem cells as a vehicle of therapeutic genes is an attractive approach for the development of new antitumoral strategies based on gene therapy.
The aim of our study was to assess the potential of bone marrow-derived Multipotent Adult Progenitor Cells (rMAPCs) to differentiate in vitro and in vivo into endothelial cells and to be recruited to areas of tumor vasculogenesis. In vitro, rMAPCs obtained from Buffalo rats differentiated into cells expressing endothelial markers and demonstrated functional endothelial capacity. Intravenous injection of undifferentiated rMAPC transduced with a lentivirus expressing GFP in an orthotopic rat model of hepatocellular carcinoma, resulted in tumor recruitment of the injected cells and in vivo differentiation into endothelial cells in the tumor area with contribution to vasculogenesis.
In summary, our results suggest that rMAPCs can be efficiently recruited by vascularized tumors and differentiate to endothelium and thus may represent a useful vehicle for delivery of therapeutic genes to sites of active tumor neovascularization.
CITATION Biochem Biophys Res Commun. 2007 Dec 7;364(1):92-9