title: Local application of adipose-derived mesenchymal stem cells supports the healing of fistula: prospective randomised study on rat model of fistulising Crohn's disease.
abstract: OBJECTIVE
  Local application of adipose-derived mesenchymal stem cells (ADSC) represents a novel approach for the management of perianal fistula in patients with Crohn's disease. A randomised study on an animal model was performed to investigate the efficacy and to detect the distribution of implanted ADSCs by bioluminescence (BLI).
  
  
  METHODS
  A caecostomy was used as a fistula model in 32 Lewis rats. The ADSCs were isolated from transgenic donor expressing firefly luciferase. Animals were randomly assigned to groups given injections of 4 × 106cells (n = 16, group A) or placebo (n = 16, group B) in the perifistular tissue. Fistula drainage assessment was used to evaluate the fistula healing. After application of D-luciferin, cell viability and distribution was detected using an IVIS Lumina XR camera on days 0, 2, 7, 14 and 30.
  
  
  RESULTS
  The fistula was identified as healed in 6 (38%) animals in group A vs. 1 case (6.3%) in group B (p = .033). The BLI was strongest immediately after administration of ADSCs 31.2 × 104(6.09-111 × 104) p/s/cm2/sr. The fastest decrease was observed within the first 2 days when values fell by 50.2%. The BLI 30 days after injection was significantly higher in animals with healed fistulas - 8.23 × 104(1.18-16.9 × 104) vs. 1.74 × 104(0.156-6.88 × 104); p = .0393.
  
  
  CONCLUSIONS
  Local application of ADSCs resulted in significantly higher fistula closure rate on an animal model. BLI monitoring was proved to be feasible and showed rapid reduction of the ADSC mass after application. More viable cells were detected in animals with healed fistula at the end of the follow-up.
authors.affiliation: a Institute of Animal Physiology and Genetics, Czech Academy of Science, Libechov , Czech Republic.|b Department of Surgery, Royal Lancaster Infirmary , University Hospitals of Morecambe Bay NHS Foundation Trust , Lancaster , UK.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Ryska
authors.affiliation: c Department of Surgery , Horovice Hospital , Horovice , Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Serclova
authors.affiliation: d Department of Plastic Surgery , Hospital Bulovka , Prague , Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Mestak
authors.affiliation: e Department of Burns Medicine , Third Faculty of Medicine Charles University , Prague , Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Matouskova
authors.affiliation: d Department of Plastic Surgery , Hospital Bulovka , Prague , Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Vesely
authors.affiliation: f Centre of Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic.
authors.forename: Iveta
authors.initials: I
authors.lastname: Mrazova
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D003424:Crohn Disease / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D008163:Luminescent Measurements; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D012003:Rectal Fistula / Q000628:therapy*; D044968:Regenerative Medicine / Q000379:methods; D016896:Treatment Outcome; D014945:Wound Healing
keywords: Mesenchymal stem cell; bioluminescence; perianal fistula