Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas

Abstract

Background: Injection of autologous adipose tissue (AT) has recently been demonstrated to be an efective and safe treatment for anal fstulas. AT mesenchymal stem cells (AT-MSCs) mediate the healing process, but the relationship between molecular characteristics of AT-MSCs of the injected AT and fstula 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 fstulas and correlate these fndings to the healing process.<p> <p>Methods: 27 patients (age 45±2 years) diagnosed with perianal fstula were enrolled in the study and treated with autologous AT injected around the anal fstula tract. AT-MSCs were isolated for cellular and molecular analyses. The fstula healing was evaluated by MRI scanning after 6 months of treatment. AT-MSC phenotype was compared between responders and non-responders with respect to fstula healing.<p> <p>Results: 52% of all patients exhibited clinical healing of the fstulas as evaluated 6 months after last injection. Cultured AT-MSCs in the responder group had a lower short-term proliferation rate and higher osteoblast diferentiation potential compared to non-responder AT-MSCs. On the other hand, adipocyte diferentiation potential of AT-MSCs was higher in non-responder group. Interestingly, AT-MSCs of responders exhibited lower expression of infammatory and senescence associated genes such as IL1B, NFKB, CDKN2A, TPB3,TGFB1.<p> <p>Conclusion: Our data suggest that cellular quality of the injected AT-MSCs including cell proliferation, diferentiation capacity and secretion of proinfammatory molecules may provide a possible mechanism underlying fstula healing. Furthermore, these biomarkers may be useful to predict a positive fstula healing outcome.