Local application of adipose-derived mesenchymal stem cells supports the healing of fistula: prospective randomised study on rat model of fistulising Crohn's disease
Language English Country England, Great Britain Media print-electronic
Document type Journal Article
- Keywords
- Mesenchymal stem cell, bioluminescence, perianal fistula,
- MeSH
- Crohn Disease complications pathology MeSH
- Wound Healing * MeSH
- Rats MeSH
- Luminescent Measurements MeSH
- Mesenchymal Stem Cells cytology MeSH
- Disease Models, Animal MeSH
- Random Allocation MeSH
- Rats, Inbred Lew MeSH
- Prospective Studies MeSH
- Regenerative Medicine methods MeSH
- Rectal Fistula therapy MeSH
- Mesenchymal Stem Cell Transplantation * MeSH
- Adipose Tissue cytology MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
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). MATERIALS AND 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 × 106 cells (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.
c Department of Surgery Horovice Hospital Horovice Czech Republic
Department of Plastic Surgery Hospital Bulovka Prague Czech Republic
e Department of Burns Medicine 3rd Faculty of Medicine Charles University Prague Czech Republic
Institute of Animal Physiology and Genetics Czech Academy of Science Libechov Czech Republic
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