Investigating the Immuno-modulatory Effect of Adipose-derived Stem Cells in Radiation- Induced Fibrosis

Abstract Background and Introduction Radiation-induced fibrosis (RIF) is a complication of radiotherapy in the treatment of head and neck carcinoma with high patient morbidity. Autologous fat grafting is a viable method to treat RIF, and adipose-derived stem cells (ADSC) were found to be one of the main components to contribute to that effect. Method Experimental group consists of irradiated human-derived fibroblasts (iHDF) in vitro with the control group unexposed to radiation. Both groups were then inoculated with ADSC-controlled media and co-culture with ADSC, whilst levels of key immunomodulators expressed by iHDF cells were obtained and measured via enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (RT-PCR). Results There is marginal decrease in CCL2 concentrations in co-cultured iHDF samples compared to untreated iHDF samples (p = 0.0006). There is a slight increase in CCL3 levels in iHDF co-culture samples compared to untreated iHDF samples (p = 0.0247). iHDF co-culture samples shows a statistically significant increase in IL-8 levels when compared to untreated samples of iHDF (p = 0.027). Col1A1 is reduced in iHDF samples when compared to control groups. Discussion CCL2 is implicated in recruitment of ADSCs to target sites. The increase in IL-8 secretion in ADSC samples is implicated in the pro-angiogenic properties of ADSC secretions to encourage healing in fibrotic tissue. Conclusion ADSC was demonstrated to have anti-fibrotic capabilities by promoting pro- angiogenic factors, however, experimental evidence points to a simultaneous increase in pro-inflammatory factors. Future works required to further investigate in vivo effects of ADSC.