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Originally published online as doi:10.2353/ajpath.2007.070066 on November 30, 2007

Published online before print November 30, 2007
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(American Journal of Pathology. 2007;171:2048-2057.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070066

Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis

John A. Rophael*, Randall O. Craft{dagger}, Jason A. Palmer*, Alan J. Hussey*, Gregory P.L. Thomas*, Wayne A. Morrison*, Anthony J. Penington* and Geraldine M. Mitchell*

From the Bernard O’Brien Institute of Microsurgery and the University of Melbourne Department of Surgery,* St. Vincent’s Hospital, Melbourne, Australia; and the Mayo Clinic Arizona,{dagger} Phoenix, Arizona

De novo tissue generation stimulated by three angiogenic growth factors administered in a factorial design was studied in an in vivo murine tissue engineering chamber. A silicone chamber was implanted around the epigastric pedicle and filled with Matrigel with 100 ng/ml of recombinant mouse vascular endothelial growth factor-120 (VEGF120), recombinant human basic fibroblastic growth factor (FGF-2), or recombinant rat platelet-derived growth factor-BB (PDGF-BB) added as single, double, or triple combinations. Angiogenesis, supporting tissue ingrowth, and adipogenesis were assessed at 2 and 6 weeks by immunohistochemistry and morphometry. At 2 weeks angiogenesis was synergistically enhanced by VEGF120 + FGF-2 (P = 0.019). FGF-2 (P = 0.008) and PDGF-BB (P = 0.01) significantly increased connective tissue/inflammatory cell infiltrate (macrophages, pericytes, and preadipocytes) in double and triple combinations compared with control. At 6 weeks sequential addition of growth factors increased the percent volume of adipose tissue (P < 0.0005, each main effect), with a synergistic increase in adipose tissue in combination treatments (P < 0.0005). Groups containing 300 ng/ml of single growth factors produced significantly less adipose tissue than the triple growth factor combination (P < 0.0005, VEGF120 and PDGF-BB; P < 0.001, FGF-2). In conclusion, angiogenic growth factor combinations increased early angiogenesis and cell infiltration resulting in synergistically increased adipose tissue growth at 6 weeks. Two way and higher level synergies are likely to be important in therapeutic applications of angiogenic growth factors.




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E. Polykandriotis, A. Arkudas, R. E. Horch, U. Kneser, and G. Mitchell
To Matrigel or Not to Matrigel
Am. J. Pathol., May 1, 2008; 172(5): 1441 - 1442.
[Abstract] [Full Text] [PDF]


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