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Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas
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SYSNO ASEP 0549766 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas Author(s) Tencerová, Michaela (FGU-C) RID, ORCID
Lundby, L. (DK)
Buntzen, S. (DK)
Norderval, S. (NO)
Hougaard, H. T. (DK)
Pedersen, B. G. (DK)
Kassem, M. (DK)Article number 586 Source Title Stem Cell Research & Therapy. - : BioMed Central
Roč. 12, č. 1 (2021)Number of pages 12 s. Language eng - English Country GB - United Kingdom Keywords autologous adipose tissue graft injection ; transsphincteric perianal fistula ; adipose-derived mesenchymal stem cells ; stem cell potency ; fistula healing Subject RIV EA - Cell Biology OECD category Cell biology Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000722212900002 EID SCOPUS 85119874897 DOI 10.1186/s13287-021-02644-8 Annotation 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2022 Electronic address https://doi.org/10.1186/s13287-021-02644-8
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