title: The adipogenic potential of various extracellular matrices under the influence of an angiogenic growth factor combination in a mouse tissue engineering chamber.
abstract: The extracellular matrix (ECM) Matrigel™ has frequently and successfully been used to generate new adipose tissue experimentally, but is unsuitable for human application. This study sought to compare the adipogenic potential of a number of alternative, biologically derived or synthetic ECMs with potential for human application, with and without growth factors and a small fat autograft. Eight groups, with six severe combined immunodeficient (SCID) mice per group, were created with bilateral chambers (silicone tubes) implanted around the epigastric vascular pedicle, with one chamber/animal containing a 5mg fat autograft. Two animal groups were created for each of four ECMs (Matrigel™, Myogel, Cymetra® and PuraMatrix™) which filled the bilateral chambers. One group/ECM had no growth factors added to chambers whilst the other group had growth factors (GFs) (vascular endothelial growth factor-A (VEGF-A) plus fibroblast growth factor-2 (FGF-2) plus platelet-derived growth factor-BB (PDGF-BB)) added to both chambers. At 6weeks, chamber tissue was morphometrically assessed for percent and absolute adipose tissue volume. Overall, the triple GF regime significantly increased percent(∗) and absolute(#) adipose tissue volume (p<0.0005(∗#)) compared to chambers without triple GF treatment. The fat autograft also significantly increased percent (p<0.0005) and absolute (p<0.011) adipose tissue volume. Cymetra® (human collagen) constructs yielded the largest total tissue and absolute adipose tissue volume. We found that the pro-angiogenic FGF-2, VEGF-A and PDGF-BB combination in ECMs of synthetic and biological origin produced an overall significantly increased adipose tissue volume at 6weeks and may have clinical application, particularly with Cymetra.
authors.affiliation: O'Brien Institute, 42 Fitzroy Street, Fitzroy, Victoria 3065, Australia.
authors.forename: Adrian C H
authors.initials: AC
authors.lastname: Ting
authors.affiliation: Banner MD Anderson Cancer Center, Gilbert, AZ, USA.
authors.forename: Randall O
authors.initials: RO
authors.lastname: Craft
authors.affiliation: O'Brien Institute, 42 Fitzroy Street, Fitzroy, Victoria 3065, Australia; Health Sciences Faculty, Australian Catholic University, 115 Victoria Parade, Fitzroy, Victoria 3065, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Palmer
authors.affiliation: O'Brien Institute, 42 Fitzroy Street, Fitzroy, Victoria 3065, Australia; Health Sciences Faculty, Australian Catholic University, 115 Victoria Parade, Fitzroy, Victoria 3065, Australia.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Gerrand
authors.affiliation: O'Brien Institute, 42 Fitzroy Street, Fitzroy, Victoria 3065, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Penington
authors.affiliation: O'Brien Institute, 42 Fitzroy Street, Fitzroy, Victoria 3065, Australia; Department of Surgery, St Vincent's Hospital, University of Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia; Health Sciences Faculty, Australian Catholic University, 115 Victoria Parade, Fitzroy, Victoria 3065, Australia.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Morrison
authors.affiliation: O'Brien Institute, 42 Fitzroy Street, Fitzroy, Victoria 3065, Australia; Department of Surgery, St Vincent's Hospital, University of Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia; Health Sciences Faculty, Australian Catholic University, 115 Victoria Parade, Fitzroy, Victoria 3065, Australia. Electronic address: geraldine.mitchell@svhm.org.au.
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: Mitchell
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D001808:Blood Vessels / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007797:Laminin / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009929:Organ Size / Q000187:drug effects; D011509:Proteoglycans / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D051381:Rats; D013194:Staining and Labeling; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D043925:Angiogenesis Inducing Agents; D004338:Drug Combinations; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D011509:Proteoglycans; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D000077214:Becaplermin; D003094:Collagen
keywords: Adipogenesis; Angiogenic growth factors; Extracellular matrices; Fat autograft; Tissue engineering chamber