Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas.
Stem Cell Res Ther
; 12(1): 586, 2021 11 24.
Article
em En
| MEDLINE
| ID: mdl-34819138
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fístula Retal
/
Transplante de Células-Tronco Mesenquimais
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Células-Tronco Mesenquimais
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Humans
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Middle aged
Idioma:
En
Revista:
Stem Cell Res Ther
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Dinamarca