| Autor: |
Frommer ML; Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UK.; Department of Surgical Biotechnology, Division of Surgery & Interventional Science, University College London, London NW3 2QG, UK.; Department of Plastic Surgery, Royal Free Hospital, London NW3 2QG, UK., Langridge BJ; Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UK.; Department of Surgical Biotechnology, Division of Surgery & Interventional Science, University College London, London NW3 2QG, UK.; Department of Plastic Surgery, Royal Free Hospital, London NW3 2QG, UK., Awad L; Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UK.; Department of Plastic Surgery, Royal Free Hospital, London NW3 2QG, UK., Jasionowska S; Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UK.; Department of Plastic Surgery, Royal Free Hospital, London NW3 2QG, UK., Denton CP; Centre for Rheumatology, Department of Inflammation, Division of Medicine, University College London, London NW3 2QG, UK., Abraham DJ; Centre for Rheumatology, Department of Inflammation, Division of Medicine, University College London, London NW3 2QG, UK., Abu-Hanna J; Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UK.; Division of Medical Sciences, University of Oxford, Oxford OX3 9DU, UK., Butler PEM; Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UK.; Department of Surgical Biotechnology, Division of Surgery & Interventional Science, University College London, London NW3 2QG, UK.; Department of Plastic Surgery, Royal Free Hospital, London NW3 2QG, UK. |
| Abstrakt: |
Adipose-derived stem cells (ADSCs) as part of autologous fat grafting have anti-fibrotic and anti-inflammatory effects, but the exact mechanisms of action remain unknown. By simulating the interaction of ADSCs with fibroblasts and endothelial cells (EC) from scleroderma (SSc) skin in silico, we aim to unravel these mechanisms. Publicly available single-cell RNA sequencing data from the stromal vascular fraction of 3 lean patients and biopsies from the skin of 10 control and 12 patients with SSc were obtained from the GEO and analysed using R and Seurat. Differentially expressed genes were used to compare the fibroblast and EC transcriptome between controls and SSc. GO and KEGG functional enrichment was performed. Ligand-receptor interactions of ADSCs with fibroblasts and ECs were explored with LIANA. Pro-inflammatory and extracellular matrix (ECM) interacting fibroblasts were identified in SSc. Arterial, capillary, venous and lymphatic ECs showed a pro-fibrotic and pro-inflammatory transcriptome. Most interactions with both cell types were based on ECM proteins. Differential interactions identified included NTN1 , VEGFD , MMP2 , FGF2, and FNDC5 . The ADSC secretome may disrupt vascular and perivascular inflammation hubs in scleroderma by promoting angiogenesis and especially lymphangiogenesis. Key phenomena observed after fat grafting remain unexplained, including modulation of fibroblast behaviour. |
