title: Growth factors adsorbed on polyglycolic acid mesh augment growth of bioengineered intestinal neomucosa.
abstract: Production of tissue engineered small intestine (TESI) has been limited by the relatively large amount of native tissue required to generate neomucosa. The influence of growth factors and three-dimensional (3D) extracellular matrices on TESI has been studied both in vitro and in vivo, and positive growth effects on tissue mass and differentiation were noted. The present study investigates the impact of single doses of glucagon-like peptide-2 (GLP-2), hepatocyte growth factor (HGF), or holo-transferrin adsorbed onto a polyglycolic (PGA) mesh scaffold using a rat small-intestinal organoid transplant model. In Experiment I, intestinal organoids were seeded onto PGA mesh discs, suspended in either Matrigel (n=8) or a vehicle control (n=8), and implanted into syngenic recipients. In Experiment II, GLP-2 (n=8), HGF (n=8), or transferrin (n=8) were adsorbed onto PGA mesh discs. Intestinal organoids were then suspended in Matrigel and seeded onto each growth factor-loaded PGA disc or onto control discs without growth factors (n=12). In addition, organoids were suspended in vehicle and seeded onto control discs (n=12). All discs were implanted into syngenic recipients. After 4 wk, histologic analysis of the samples revealed significantly greater neomucosal surface area (3.62±0.33 mm(2)versus 0.92±0.11 mm(2), P<0.0001) and cyst diameter (2.83±0.14 mm versus 2.06±0.07 mm, P<0.0001) in groups treated with Matrigel compared with vehicle controls. The addition of holo-transferrin to the scaffolds further augmented neomucosal surface area (9.11±0.66 mm(2)versus 3.01±0.22 mm(2), P<0.01), whereas that of GLP-2 stimulated the formation of increased numbers of cysts (8.88±0.46 versus 4.18±0.25, P<0.01). These data suggest that Matrigel and growth factors adsorbed to polymer scaffolds can be used to manipulate the morphology of TESI.
authors.affiliation: Department of Surgery, VA Greater Los Angeles Health Care System, Los Angeles, California 90073, USA.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Wulkersdorfer
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Kao
authors.forename: Vatche G
authors.initials: VG
authors.lastname: Agopian
authors.forename: James C
authors.initials: JC
authors.lastname: Dunn
authors.forename: Ben M
authors.initials: BM
authors.lastname: Wu
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelzner
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057005:Bioengineering / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D010865:Pilot Projects; D011100:Polyglycolic Acid; D051381:Rats; D011917:Rats, Inbred Lew; D013526:Surgical Mesh; D014168:Transferrin / Q000494:pharmacology
chemical_list: D053767:Glucagon-Like Peptide 2; D036341:Intercellular Signaling Peptides and Proteins; D014168:Transferrin; C110714:holotransferrin; D011100:Polyglycolic Acid; D017228:Hepatocyte Growth Factor