Authors: Albert Boronat-Toscano, Irene Vañó, Diandra Monfort-Ferré, Margarita Menacho, Gemma Valldosera, Aleidis Caro, Beatriz Espina, Maria José Mañas, Marc Marti, Eloy Espin, Alfonso Saera-Vila, Carolina Serena


  • Hospital Universitari de Tarragona Joan XXIII, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, 43007 Tarragona, Spain
  • Digestive Unit, Hospital Universitari Joan XXIII, 43007 Tarragona, Spain
  • Colorectal Surgery Unit, Hospital Universitari Joan XXIII, 43007 Tarragona, Spain
  • Colorectal Surgery Unit, Hospital San Pau i Santa Tecla, 43003 Tarragona, Spain
  • Colorectal Surgery Unit, General Surgery Service, Hospital Vall de Hebron, Universitat Autonoma de Barcelona, 08035 Barcelona, Spain
  • Sequentia Biotech, Carrer Comte D’Urgell 240, 08036 Barcelona, Spain

Publication: MDPI

Date: March, 2023

Link: Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn’s Disease Patients through Epigenetic Changes


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.