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.