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 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 A...

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Autores principales:	Michaela Tencerova, Lilli Lundby, Steen Buntzen, Stig Norderval, Helene Tarri Hougaard, Bodil Ginnerup Pedersen, Moustapha Kassem
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Autologous adipose tissue graft injection Transsphincteric perianal fistula Adipose-derived mesenchymal stem cells Stem cell potency Fistula healing Medicine (General) R5-920 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/7440f50bd41149eea4b633ab1aa39ce3
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spelling	oai:doaj.org-article:7440f50bd41149eea4b633ab1aa39ce32021-11-28T12:06:26ZMolecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas10.1186/s13287-021-02644-81757-6512https://doaj.org/article/7440f50bd41149eea4b633ab1aa39ce32021-11-01T00:00:00Zhttps://doi.org/10.1186/s13287-021-02644-8https://doaj.org/toc/1757-6512Abstract 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/NCT04834609Michaela TencerovaLilli LundbySteen BuntzenStig NordervalHelene Tarri HougaardBodil Ginnerup PedersenMoustapha KassemBMCarticleAutologous adipose tissue graft injectionTranssphincteric perianal fistulaAdipose-derived mesenchymal stem cellsStem cell potencyFistula healingMedicine (General)R5-920BiochemistryQD415-436ENStem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Autologous adipose tissue graft injection Transsphincteric perianal fistula Adipose-derived mesenchymal stem cells Stem cell potency Fistula healing Medicine (General) R5-920 Biochemistry QD415-436
spellingShingle	Autologous adipose tissue graft injection Transsphincteric perianal fistula Adipose-derived mesenchymal stem cells Stem cell potency Fistula healing Medicine (General) R5-920 Biochemistry QD415-436 Michaela Tencerova Lilli Lundby Steen Buntzen Stig Norderval Helene Tarri Hougaard Bodil Ginnerup Pedersen Moustapha Kassem Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas
description	Abstract 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
format	article
author	Michaela Tencerova Lilli Lundby Steen Buntzen Stig Norderval Helene Tarri Hougaard Bodil Ginnerup Pedersen Moustapha Kassem
author_facet	Michaela Tencerova Lilli Lundby Steen Buntzen Stig Norderval Helene Tarri Hougaard Bodil Ginnerup Pedersen Moustapha Kassem
author_sort	Michaela Tencerova
title	Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas
title_short	Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas
title_full	Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas
title_fullStr	Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas
title_full_unstemmed	Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas
title_sort	molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas
publisher	BMC
publishDate	2021
url	https://doaj.org/article/7440f50bd41149eea4b633ab1aa39ce3
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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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