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

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  • Michaela Tencerova, Syddansk Universitet, Czech Academy of Sciences
  • ,
  • Lilli Lundby
  • ,
  • Steen Buntzen, University Hospital North Norway, Tromsø, Norway. , UiT Arctic Univ Norway, UiT The Arctic University of Tromso, Inst Arctic & Marine Biol
  • ,
  • Stig Norderval, UiT The Arctic University of Norway
  • ,
  • Helene Tarri Hougaard
  • Bodil Ginnerup Pedersen
  • Moustapha Kassem, Syddansk Universitet, Københavns Universitet

BACKGROUND: Injection 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.

METHODS: 27 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.

RESULTS: 52% 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.

CONCLUSION: Our 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.

OriginalsprogEngelsk
Artikelnummer586
TidsskriftStem Cell Research & Therapy
Vol/bind12
Antal sider12
ISSN1757-6512
DOI
StatusUdgivet - nov. 2021

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© 2021. The Author(s).

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