Multipotent Adult Progenitor Cells (MAPC) contribute to hepatocarcinoma neovasculature.
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.
Barajas
Miguel
M
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.
Franchi
Federico
F
Clavel
Carlos
C
Aranguren
Xabier L
XL
Kramer
M Gabriela
MG
Abizanda
Gloria
G
Merino
Juana
J
Moreno
Cristina
C
Gárate
Leire
L
Guitart
Anunciata
A
Narvaiza
Iñigo
I
Gutiérrez-Perez
María
M
Riezu-Boj
Jose-Ignacio
JI
Berasain
Carmen
C
Prieto
Jesús
J
Prósper
Felipe
F
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000166:cytology; D015316:Genetic Therapy / Q000379:methods; D008114:Liver Neoplasms, Experimental / Q000098:blood supply*; D008297:Male; D039902:Multipotent Stem Cells / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D051381:Rats