INVESTIGADORES
PODHAJCER Osvaldo Luis
artículos
Título:
A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus
Autor/es:
BOLONTRADE MF; SGANGA L; PIAGGIO, EDUARDO; VIALE DL; SORRENTINO, MIGUEL A; ROBINSON, ANIBAL; SEVLEVER G; GARCIA M; MAZZOLINI GM; PODHAJCER OL
Revista:
STEM CELLS AND DEVELOPMENT
Editorial:
MARY ANN LIEBERT INC
Referencias:
Lugar: New York; Año: 2012 vol. 21 p. 2689 - 2702
ISSN:
1547-3287
Resumen:
The homing properties of mesenchymal stromal cells (MSCs) toward tumors
turn them into attractive tools for combining cell and gene therapy. The
aim of this study was to select in a feasible way a human bone
marrow-derived MSC subpopulation that might exhibit a selective ability
to target the tumor mass. Using differential in vitro adhesive
capacities during cells isolation, we selected a specific MSC
subpopulation (termed MO-MSCs) that exhibited enhanced multipotent
capacity and increased cell surface expression of specific integrins
(integrins α2, α3, and α5), which correlated with an enhanced MO-MSCs
adhesiveness toward their specific ligands. Moreover, MO-MSCs exhibited a
higher migration toward conditioned media from different cancer cell
lines and fresh human breast cancer samples in the presence or not of a
human microendothelium monolayer. Further in vivo studies demonstrated
increased tumor homing of MO-MSCs toward established 578T and MD-MBA-231
breast cancer and A375N melanoma tumor xenografts. Tumor penetration by
MO-MSCs was highly dependent on metallopeptidases production as it was
inhibited by the specific inhibitor 1,10 phenantroline. Finally,
systemically administered MO-MSCs preloaded with an oncolytic adenovirus
significantly inhibited tumor growth in mice harboring established
A375N melanomas, overcoming the natural resistance of the tumor to in
situ administration of the oncolytic adenovirus. In summary, this work
characterizes a novel MSC subpopulation with increased tumor homing
capacity that can be used to transport therapeutic compounds.