Abstract
Background: Local application of adipose-derived mesenchymal stem cells (ADSCs) is a promising method for the treatment of perianal fistula in patients with Crohn's disease. There is a lack of data evaluating the distribution and viability of ADSCs after application. Therefore more studies are needed including the technique of in vivo monitoring. Aim: The aim of the study was to evaluate the effect of ADSCs application on fistula healing regarding their viability and distribution in perifistular region. Methods: Coecostomy was used as a fistula model in Lewis rats. The inguinal adipose tissue was harvested from transgenic donor expressing firefly luciferase (LEW-Tg(Rosa-luc)11Jmsk; Jichi Medical School, Japan). The ADSCs were isolated using collagenase technique and injected (1-2*106 cells/ml) in perifistular tissue of 16 rats. After application of D-luciferin (25mg/kg), animals were imaged in IVIS Lumina XR camera on days 0, 2, 7, 14 and 30. Fistula drainage assessment (FDA) was used to evaluate the fistula healing. Animals from interventional group were compared to 30 rats with untreated fistula. Results: There was no morbidity or mortality after intervention. The fistula was identified as healed according to FDA in 6 (37.5%) animals after ADSCs injection vs. 1 case (3.3%) with spontaneous closure in control group (p< 0.0047). Bioluminescence was strongest 2 days after application (31.2*104 (6.10-11.0*104). The amount of viable cells remained stable during first 7 days, which confirms successful cells seating. The signal started to decrease slowly afterwards day 14: 6.4*104 (0.5-28.8*104) and day 30: 2.8*104 (0.16-16.9*104) (values are medians in p/s/cm2/sr) (fig.1). The luminescence 30 days after injection was significantly higher in animals with healed fistula 8.23*104 (1.18*1041.70*105) vs. 2.75*104 (4.93*103-6.88*104); p=0.18. Conclusion: Perifistular application of ADSCs and in vivo monitoring using bioluminescence are technically feasible and doesn't cause mortality or morbidity. Local treatment with ADSCs led to significantly more frequent fistula closure compared to the control group. The fistula healing was associated with significantly higher concentration of viable ADSCs in perifistular region, which was confirmed by stronger bioluminescence signal. Supported by NT13708
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