Characterization of adipose tissue and adipose-tissue derived stem cells in Lipedema

Purpose: Lipedema is a painful adipose tissue (AT) disorder that occurs almost exclusively in women, with onset manifesting at puberty or at times of hormonal change. This disorder is characterized by a symmetrical increase of fat deposition in the legs and the arms, sparing the hands and the feet. The goal of this study was to determine the histology of the skin and fat of lipedema tissue and characterize the adipose tissue-derived stem cells (ASCs) obtained from the stromal vascular fraction (SVF) of thigh AT of non-lipedema and lipedema patients. Methods: Histological sections from AT were stained with H&E. Adipocyte area was quantified using ImageJ software. Markers for macrophages (CD68) was investigated by immunohistochemistry. ASCs were characterized by the expression of stemness markers and their multi-differentiation potential. Flow cytometry, RT-PCR and immunofluorescence assays were performed. Results: The data show hypertrophic adipocytes, increased numbers of macrophages and blood vessels in thigh tissue of women with lipedema compared to non-lipedema patients. Additionally, at the cellular level, an increase in the adipogenic differentiation potential with no change in the expression of mesenchymal markers (CD73, CD90 and CD105) or extracellular markers (collagen, fibronectin and laminin) was detected in lipedema ASCs compared to non-lipedema ASCs. Conclusion: Infiltration of immune cells, increase in adipocyte size and adipogenesis stimulates angiogenesis and fibrosis in lipedema AT. Defining the structure and the components of AT will provide insights into the pathophysiology of lipedema and will help researchers develop potential treatment for the disease.