Abstract Background Radiation-induced fibrosis (RIF) is a debilitating complication following radiotherapy, characterised by fibroblast proliferation and excessive extracellular matrix (ECM) deposition, leading to functional and aesthetic impairments. Although autologous fat grafting (AFG) has shown promise in reversing RIF, the mechanisms, largely attributed to adipose-derived stem cells (ADSCs), remain elusive. This study aimed to investigate ADSCs’ and their secretome on ECM remodelling in RIF management. Methods The anti-fibrotic potential of the ADSC secretome on HDFs subjected to ionising radiation was assessed via a series of in vitro experiments. Control HDFs were compared with irradiated HDFs to assess any phenotypical changes. Irradiated HDFs were treated with ADSC pre-conditioned media (CM) or ADSC co-culture (CC). Gene expression (COL1A1, TGF-β, CCN-2, MMP-1, MMP-3, TIMP-1, ACTA2, TNC) was assessed via real-time quantitative PCR (RT-qPCR). ProCollagen1a1 and CCN2 protein concentrations were assessed by ELISA. Results Irradiated HDFs demonstrated changes in fibrotic gene expression. ADSC-CM treatment significantly reduced COL1A1 expression, although protein levels remained unchanged. TGF-β1, CCN2, MMP-3, TIMP-1 and ACTA-2 exhibited reduced expression post-ADSC-CM treatment whereas TNC expression was found to be significantly increased. Co-culture with ADSCs led to a general, but not statistically significant, decrease in pro-fibrotic gene expression. Notably, CCN-2 protein expression significantly increased. Conclusion This study demonstrates that ionising radiation results in a pathological pro-fibrotic phenotype in HDFs. The ADSC secretome potentially mitigates this, reducing pro-fibrotic gene expression. Unexpectedly, co-culture experiments highlighted a complex interaction with upregulation of fibrosis-associated genes. Further research is needed to clarify these interactions to improve therapeutic interventions for RIF.
Abstract Aim This audit aimed to evaluate and improve the results of microvascular breast free flap reconstruction by implementing an enhanced perioperative care approach. Method All microvascular breast free flap reconstructions between June to August 2023 were included. Additionally, a three year retrospective review was conducted in adherence to ABS and the BAPRAS guidelines. Our team plans to introduce an evidenced-based modified Enhanced Recovery After Surgery (ERAS) protocol via MDT collaboration with a focus on pre-operative and post-operative care to improve postoperative outcomes. Results During June – August 2023, 22 flaps were performed with an average length of stay (LOS) of 5.47 days (target <3d). There were no unplanned readmissions, an 18% return to theatre (RTT) rate and a total complication rate of 18%. Over the past three years, out of 323 flaps, there was a 13% RTT rate with no unplanned readmissions. Suggested modifications to reduce length of stay include pre-surgical counselling and nutritional loading. Post-operatively, using a multi-modal opioid sparing analgesia (MOSA) regime, along with laxatives, early mobilisation and feeding has proven to enhance recovery. Pre-admission patient optimisation, VTE and perioperative antibiotic prophylaxis have been shown to reduce rates of flap failures and post-operative complications. Effective wound care, post-discharge support and physiotherapy are also crucial in accelerating recovery and preventing readmissions. Conclusion Implementing these ERAS modification to our current protocol is predicted to significantly improve post-operative recovery, thus improving surgical outcomes. This underscores the potential for continual improvement in patient care through an efficient evidence-based perioperative pathway.
Abstract Background Radiation-induced fibrosis (RIF) is a debilitating complication following radiotherapy, characterised by fibroblast proliferation and excessive extracellular matrix (ECM) deposition, leading to functional and aesthetic impairments. Although autologous fat grafting (AFG) has shown promise in reversing RIF, the mechanisms, largely attributed to adipose-derived stem cells (ADSCs), remain elusive. This study aimed to investigate ADSCs’ and their secretome on ECM remodelling in RIF management. Methods The anti-fibrotic potential of the ADSC secretome on HDFs subjected to ionising radiation was assessed via a series of in vitro experiments. Control HDFs were compared with irradiated HDFs to assess any phenotypical changes. Irradiated HDFs were treated with ADSC pre-conditioned media (CM) or ADSC co-culture (CC). Gene expression (COL1A1, TGF-β1, CCN-2, MMP-1, MMP-3, TIMP-1, ACTA2, TNC) was assessed via real-time quantitative PCR (RT-qPCR). ProCollagen1a1 and CCN2 protein concentrations were assessed by ELISA. Results Irradiated HDFs demonstrated changes in fibrotic gene expression. ADSC-CM treatment significantly reduced COL1A1 expression, although protein levels remained unchanged. TGF-β1, CCN2, MMP-3, TIMP-1 and ACTA-2 exhibited reduced expression post-ADSC-CM treatment whereas TNC expression was found to be significantly increased. Co-culture with ADSCs led to a general, but not statistically significant, decrease in pro-fibrotic gene expression. Notably, CCN-2 protein expression significantly increased. Conclusion This study demonstrates that ionising radiation results in a pathological pro-fibrotic phenotype in HDFs. The ADSC secretome potentially mitigates this, reducing pro-fibrotic gene expression. Unexpectedly, co-culture experiments highlighted a complex interaction with upregulation of fibrosis-associated genes. Further research is needed to clarify these interactions to improve therapeutic interventions for RIF.
Abstract Aim Radiation-induced fibrosis (RIF) is a debilitating complication following radiotherapy, characterised by fibroblast proliferation and excessive extracellular matrix (ECM) deposition, leading to functional and aesthetic impairments. Although autologous fat grafting (AFG) has shown promise in reversing RIF, the mechanisms, largely attributed to adipose-derived stem cells (ADSCs), remain elusive. This study aimed to investigate ADSCs’ and their secretome on ECM remodelling in RIF management. Method The anti-fibrotic potential of the ADSC secretome on human dermal fibroblasts (HDFs) subjected to ionising radiation was assessed via a series of in vitro experiments. Control HDFs were compared with irradiated HDFs to assess any phenotypical changes. Irradiated HDFs were treated with ADSC pre-conditioned media (CM) or ADSC co-culture (CC). Gene expression (COL1A1, TGF-β1, CCN-2, MMP-1, MMP-3, TIMP-1, ACTA2, TNC) was assessed via real-time quantitative PCR (RT-qPCR). ProCollagen1a1 and CCN2 protein concentrations were assessed by ELISA. Results Irradiated HDFs demonstrated changes in fibrotic gene expression. ADSC-CM treatment significantly reduced COL1A1 expression, although protein levels remained unchanged. TGF-β1, CCN2, MMP-3, TIMP-1 and ACTA-2 exhibited reduced expression post-ADSC-CM treatment whereas TNC expression was found to be significantly increased. Co-culture with ADSCs led to a general, but not statistically significant, decrease in pro-fibrotic gene expression. Notably, CCN-2 protein expression significantly increased. Conclusions This study demonstrates that ionising radiation results in a pathological pro-fibrotic phenotype in HDFs. The ADSC secretome potentially mitigates this, reducing pro-fibrotic gene expression. Unexpectedly, co-culture experiments highlighted a complex interaction with upregulation of fibrosis-associated genes. Further research is needed to clarify these interactions to improve therapeutic interventions for RIF.
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