Determination of adipogenesis stages of human umbilical cord-derived mesenchymal stem cells using three-dimensional label-free holotomography

Methods. 2024 Nov:231:204-214. doi: 10.1016/j.ymeth.2024.10.005. Epub 2024 Oct 11.

Abstract

Adipogenesis involves complex changes in gene expression, morphology, and cytoskeletal organization. However, the quantitative analysis of live cell images to identify their stages through morphological markers is limited. Distinct adipogenesis markers on human umbilical cord-derived mesenchymal stem cells (UC-MSCs) were identified through holotomography, a label-free live cell imaging technique. In the MSC-to-preadipocyte transition, the nucleus-to-cytoplasm ratio (0.080 vs. 0.052) and lipid droplet (LD) refractive index variation decreased (0.149 % vs. 0.061 %), whereas the LD number (20 vs. 65) increased. This event was also accompanied by the downregulation and upregulation of THY1 and Preadipocyte Factor-1 (PREF-1), respectively. In the preadipocyte to immature adipocyte shift, cell sphericity (0.20 vs. 0.43) and LD number (65 vs. 200) surged, large LDs (>10 μm3) appeared, and the major axis of the cell was reduced (143.7 μm vs. 83.12 μm). These findings indicate features of preadipocyte and immature adipocyte stages, alongside the downregulation of PREF-1 and upregulation of Peroxisome Proliferator-Activated Receptor gamma (PPARγ). In adipocyte maturation, along with PPARγ and Fatty Acid-Binding Protein 4 upregulation, cell compactness (0.15 vs. 0.29) and sphericity (0.43 vs. 0.59) increased, and larger LDs (>30 μm3) formed, marking immature and mature adipocyte stages. The study highlights the distinct adipogenic morphological biomarkers of adipogenesis stages in UC-MSCs, providing potential applications in biomedical and clinical settings, such as fostering innovative medical strategies for treating metabolic disease.

Keywords: Adipogenesis; Differentiation stage; Holotomography; Morphological markers; UC-MSCs.

MeSH terms

  • Adipocytes* / cytology
  • Adipocytes* / metabolism
  • Adipogenesis*
  • Calcium-Binding Proteins
  • Cell Differentiation
  • Cells, Cultured
  • Humans
  • Imaging, Three-Dimensional / methods
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lipid Droplets / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Thy-1 Antigens / genetics
  • Thy-1 Antigens / metabolism
  • Umbilical Cord* / cytology
  • Umbilical Cord* / metabolism

Substances

  • Thy-1 Antigens
  • DLK1 protein, human
  • Membrane Proteins
  • Intercellular Signaling Peptides and Proteins
  • PPAR gamma
  • Calcium-Binding Proteins