A cell-based multifactorial approach to angiogenesis.
We here propose an alternative cell therapy approach to induce angiogenesis. We prepared small organ fragments whose geometry allows preservation of the natural epithelial/mesenchymal interactions and ensures appropriate diffusion of nutrients and gases to all cells. Fragments derived from lung are shown to behave as fairly independent units, to undergo a marked upregulation of angiogenic factors and to continue to function for several weeks in vitro in serum-free media. When implanted into hosts, they transcribe a similar array of angiogenic factors that specifically induce the formation of a potent vascular network. The angiogenic induction capacity of these fragments was also tested in a mouse and rat model of limb ischemia. We report that such fragments, when implanted in the vicinity of the ischaemic area, induce an angiogenic response which can rescue the ischaemia-induced damage. The approach presented differs from single factor application, gene therapy and other cell therapy methods in that it exploits the complex behaviour of autologous cells in their near to normal environment in order to achieve secretion of a whole range of angiogenic stimuli continuously and in an apparently coordinated fashion.
Hasson
Eilat
E
Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Arbel
Dan
D
Verstandig
Anthony
A
Shimoni
Yael
Y
Mitrani
Eduardo
E
D000818:Animals; D005121:Extremities / Q000098:blood supply; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D007511:Ischemia / Q000628:therapy; D008168:Lung / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2