3d spheroids derived from human lipedema ascs demonstrated similar adipogenic differentiation potential and ecm remodeling to non-lipedema ascs in vitro

Sara Al-Ghadban, India A. Pursell, Zaidmara T. Diaz, Karen L. Herbst, Bruce A. Bunnell

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Article number8350
Pages (from-to)1-14
Number of pages14
JournalInternational journal of molecular sciences
Volume21
Issue number21
DOIs
StatePublished - 1 Nov 2020

Keywords

  • Adipogenic differentiation
  • Adipose tissue-derived stem cells (ASCs)
  • ECM markers
  • Inflammation
  • Lipedema
  • Spheroids

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