title: Specific differences in migratory function of myofibroblasts isolated from Crohn's disease fistulae and strictures.
abstract: BACKGROUND
  Recently we found that migration of colonic lamina propria fibroblasts in Crohn's disease patients (CD-CLPF) from inflamed mucosa is significantly reduced as compared to control-CLPF. The behavior of CD-CLPFs isolated from fistulae and strictures was now investigated in detail.
  
  
  METHODS
  Initially migration assays for all CLPF cultures (CD-CLPF, fibrosis-CLPF, and fistula-CLPF) were performed in the modified 48-well Boyden chamber. Subsequently, for a migration assay more resembling the in vivo situation a 3D matrix model was developed. After seeding of cells into the 3D matrix the CLPF layer was wounded by an ERBIUM:YAG laser leading to circular cell rupture without effect on the extracellular matrix.
  
  
  RESULTS
  In the modified Boyden chamber migration of fistula-CLPF was significantly reduced compared to CD-CLPF. This was correlated with a decrease in FAK-protein expression, whereas in migrating fibrosis-CLPF an increase in FAK-protein expression, -autophosphorylation and migratory potential was found. This was confirmed in the 3D matrix wounding assay: Fistula-CLPF migrated less than CD-CLPF, whereas fibrosis-CLPF migrated significantly more in the 3D matrix wounding assay. Between 1 to 36 hours incubation time fibrosis-CLPF always displayed increased migration ability as compared to CD-CLPF. In contrast, fistula-CLPF migratory potential was always below that of CD-CLPF.
  
  
  CONCLUSIONS
  Myofibroblasts isolated from inflamed, fibrostenotic, or fistulized CD mucosa differ in their migratory potential both in the modified Boyden chamber as well as in a 3D matrix model. These different migratory behaviors could be an explanation for impaired or excess wound healing and subsequently for fistula and fibrosis formation.
authors.affiliation: Department of Cranio-Maxillo-Facial Surgery, University of Regensburg, Germany.
authors.forename: Johannes K-H
authors.initials: JK
authors.lastname: Meier
authors.forename: Michael
authors.initials: M
authors.lastname: Scharl
authors.forename: Sandra N
authors.initials: SN
authors.lastname: Miller
authors.forename: Julia
authors.initials: J
authors.lastname: Brenmoehl
authors.forename: Martin
authors.initials: M
authors.lastname: Hausmann
authors.forename: Silvia
authors.initials: S
authors.lastname: Kellermeier
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002465:Cell Movement; D002478:Cells, Cultured; D003251:Constriction, Pathologic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000150:complications* / Q000473:pathology / Q000628:therapy; D005260:Female; D005355:Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D014945:Wound Healing