Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn's Disease Patients through Epigenetic Changes
Boronat-Toscano, Albert (Hospital Universitari Joan XXIII de Tarragona)
Vañó, Irene (Institut d'Investigació Sanitària Pere Virgili)
Monfort-Ferré, Diandra (Hospital Universitari Joan XXIII de Tarragona)
Menacho, Margarita (Hospital Universitari Joan XXIII de Tarragona)
Valldosera, Gemma (Hospital Universitari Joan XXIII de Tarragona)
Caro, Aleidis (Hospital Universitari Joan XXIII de Tarragona)
Espina, Beatriz (Hospital Universitari Joan XXIII de Tarragona)
Mañas, Maria José (Hospital Sant Pau i Santa Tecla (Tarragona))
Marti-Gallostra, Marc (Hospital Universitari Vall d'Hebron)
Espin-Basany, Eloy (Hospital Universitari Vall d'Hebron)
Saera-Vila, Alfonso (Sequentia Biotech)
Serena, Carolina (Institut d'Investigació Sanitària Pere Virgili)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	Patients with Crohn's disease (CD) who smoke are known to have a worse prognosis than never-smokers and a higher risk for post-surgical recurrence, whereas patients who quit smoking after surgery have significantly lower post-operative recurrence. The hypothesis was that smoking induces epigenetic changes that impair the capacity of adipose stem cells (ASCs) to suppress the immune system. It was also questioned whether this impairment remains in ex-smokers with CD. ASCs were isolated from non-smokers, smokers and ex-smokers with CD and their interactions with immune cells were studied. The ASCs from both smokers and ex-smokers promoted macrophage polarization to an M1 pro-inflammatory phenotype, were not able to inhibit T- and B-cell proliferation in vitro and enhanced the gene and protein expression of inflammatory markers including interleukin-1b. Genome-wide epigenetic analysis using two different bioinformatic approaches revealed significant changes in the methylation patterns of genes that are critical for wound healing, immune and metabolic response and p53-mediated DNA damage response in ASCs from smokers and ex-smokers with CD. In conclusion, cigarette smoking induces a pro-inflammatory epigenetic signature in ASCs that likely compromises their therapeutic potential.
Grants:	Instituto de Salud Carlos III PI18/00037 Ministerio de Economía y Competitividad RYC2013-13186
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	DNA methylation ; Tobacco ; Cigarette ; Macrophages ; Cell therapy ; Adipose tissue ; Inflammatory bowel diseases ; Chronic inflammatory disease ; Immune cells ; Differentially methylated regions
Published in:	Cells, Vol. 12 (march 2023) , ISSN 2073-4409

DOI: 10.3390/cells12071021
PMID: 37048094

16 p, 3.3 MB

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