O163 The secretome of adipose-derived stem cells (ADSCS): exploring anti-fibrotic effects in skin fibrosis

Abstract

Abstract Introduction As part of surgical reconstruction with autologous fat grafting, ADSCs are believed to play a pivotal role in the observed anti-fibrotic effect, however, the exact mechanisms remain unknown. Here, we explored the changes in the ADSC secretome after proinflammatory and profibrotic stimulation in-vitro to gain further mechanistic insights. Methods ADSCs were obtained from five non-obese patients (BMI<30) without systemic disease (n=5). ADSCs were exposed to either TGF-β1, IL-1β, hypoxia (1%O2) or 10% fetal bovine serum (FBS) for 24 hours. 0.1%FBS was used as control group. Samples were then analysed by RT-qPCR for nine target genes. Selected targets were validated in the secretome through ELISA. Further, expression of surface markers was explored by RT-qPCR. Results VEGF, FGF2, CSF1, and CCN5 were explored at protein level. VEGF secretion increased significantly in all treatment groups. IL-1β significantly increased the production of FGF2 at protein level (p=0.043). CSF1 was secreted in similar amounts across groups. CCN5 secretion varied little, although higher amounts were detected in the 10%FBS group. Hypoxia and IL-1β increased expression of ADSC markers (CD90, CD73, CD26), while TGF-β1 and 10%FBS decreased it. However, CD105 was upregulated in the 10%FBS group. Additionally, TIMP1, MMP2, APP, and OGN were explored. Conclusion ADSCs secreted VEGF, FGF2, CCN5, and CSF1 in an in-vitro fibrotic environment. Further investigation of these pathways may lead to the development of novel treatments for fibrotic diseases such as scleroderma and radiation-induced fibrosis.