Abstract
The growth and differentiation of adipose tissue-derived stem cells (ASCs) is stimulated and regulated by the adipose tissue (AT) microenvironment. In lipedema, both inflammation and hypoxia influence the expansion and differentiation of ASCs, resulting in hypertrophic adipocytes and deposition of collagen, a primary component of the extracellular matrix (ECM). The goal of this study was to characterize the adipogenic differentiation potential and assess the levels of expression of ECM-remodeling markers in 3D spheroids derived from ASCs isolated from both lipedema and healthy individuals. The data showed an increase in the expression of the adipogenic genes (ADIPOQ, LPL, PPAR-γ and Glut4), a decrease in matrix metalloproteinases (MMP2, 9 and 11), with no significant changes in the expression of ECM markers (collagen and fibronectin), or integrin A5 in 3D differentiated lipedema spheroids as compared to healthy spheroids. In addition, no statistically significant changes in the levels of expression of inflammatory genes were detected in any of the samples. However, immunofluorescence staining showed a decrease in fibronectin and increase in laminin and Collagen VI expression in the 3D differentiated spheroids in both groups. The use of 3D ASC spheroids provide a functional model to study the cellular and molecular characteristics of lipedema AT.
Highlights
Adipose tissue-derived stem cells (ASCs) are immunologically privileged cells that have been extensively studied in regenerative medicine and tissue engineering
adipose tissue-derived stem cells (ASCs) have been implicated in the treatment of many pathological and chronic disorders such as diabetes, multiple sclerosis, neurodegenerative, Crohn’s and Graft-versus-host disease; the source of the stem cells should be carefully considered for successful outcomes
We and others have shown that stromal vascular fraction (SVF), a heterogeneous population of cells, isolated from lipedema adipose tissue (AT) and expanded in monolayer cultures, is composed of significantly higher levels of the mesenchymal stem marker (CD90; cluster of differentiation 90) and endothelial markers (CD31 and CD146) as compared to individuals unaffected with lipedema [35,36], which may be a contributing factor to the leaky blood and lymphatic vessels detected in lipedema tissues
Summary
Adipose tissue-derived stem cells (ASCs) are immunologically privileged cells that have been extensively studied in regenerative medicine and tissue engineering. Studying ASC spheroids enabled researchers to investigate ASCs in an in vivo-like cellular environment by promoting their interactions with other cells and extracellular matrix (ECM) components [18] These interactions are essential to instigate ASC differentiation into specific cell lineages such as adipocytes, osteocytes, and chondrocytes. We and others have shown that SVF, a heterogeneous population of cells, isolated from lipedema AT and expanded in monolayer cultures, is composed of significantly higher levels of the mesenchymal stem marker (CD90; cluster of differentiation 90) and endothelial markers (CD31 and CD146) as compared to individuals unaffected with lipedema [35,36], which may be a contributing factor to the leaky blood and lymphatic vessels detected in lipedema tissues. A decrease in fibronectin and an increase in laminin and Col VI proteins were detected in 3D differentiated spheroids in both groups
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