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).

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.

Keywords:

• Mesenchymal stem cell
• perianal fistula
• bioluminescence

Acknowledgements

Each author made an equal contribution to the conception and design of the study, the acquisition of data or analysis and interpretation of data, to drafting the article or revising it critically, and has approved the final version to be submitted. The authors thank the staff of the experimental centre at the Institute of Clinical and Experimental Medicine in Prague.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This work was supported by the Ministry of Health of the Czech Republic [IGA NT13708, AZV 16-31806A].