Abstract
BackgroundInjection of autologous adipose tissue (AT) has recently been demonstrated to be an effective and safe treatment for anal fistulas. AT mesenchymal stem cells (AT-MSCs) mediate the healing process, but the relationship between molecular characteristics of AT-MSCs of the injected AT and fistula healing has not been adequately studied. Thus we aimed to characterize the molecular and functional properties of AT-MSCs isolated from autologous AT injected as a treatment of cryptogenic high transsphincteric perianal fistulas and correlate these findings to the healing process.Methods27 patients (age 45 ± 2 years) diagnosed with perianal fistula were enrolled in the study and treated with autologous AT injected around the anal fistula tract. AT-MSCs were isolated for cellular and molecular analyses. The fistula healing was evaluated by MRI scanning after 6 months of treatment. AT-MSC phenotype was compared between responders and non-responders with respect to fistula healing.Results52% of all patients exhibited clinical healing of the fistulas as evaluated 6 months after last injection. Cultured AT-MSCs in the responder group had a lower short-term proliferation rate and higher osteoblast differentiation potential compared to non-responder AT-MSCs. On the other hand, adipocyte differentiation potential of AT-MSCs was higher in non-responder group. Interestingly, AT-MSCs of responders exhibited lower expression of inflammatory and senescence associated genes such as IL1B, NFKB, CDKN2A, TPB3,TGFB1.ConclusionOur data suggest that cellular quality of the injected AT-MSCs including cell proliferation, differentiation capacity and secretion of proinflammatory molecules may provide a possible mechanism underlying fistula healing. Furthermore, these biomarkers may be useful to predict a positive fistula healing outcome.Trial registration: NTC04834609, Registered 6 April 2021. https://clinicaltrials.gov/ct2/show/NCT04834609
Highlights
Perianal fistulas of crypto-glandular origin are common with an incidence of 10–23 cases/100,000/year [1]
We investigated cellular and molecular characteristics of adipose tissue (AT)-MSCs obtained from autologous AT therapy in patients with high transphincteric perianal fistulas of crytoglandular origin, which were correlated with the outcome of the fistula treatment
All fistulas were classified as high single tract transsphincteric involving more than 50% of the external anal sphincter
Summary
Perianal fistulas of crypto-glandular origin are common with an incidence of 10–23 cases/100,000/year [1]. Tencerova et al Stem Cell Research & Therapy (2021) 12:586 interventions are frequent in order to classify the fistula, establish proper drainage and promote healing. This will often have a major impact on patient’s social activity and quality of life [2]. The advancement flap has been considered as the gold standard with a success rate around 80% [3] Other techniques such as fibrin glue, collagen paste and fistula plug have success rates between 20 and 50%. We aimed to characterize the molecular and functional properties of AT-MSCs isolated from autologous AT injected as a treatment of cryptogenic high transsphincteric perianal fistulas and correlate these findings to the healing process
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