Three-Dimensional Culture Decreases the Angiogenic Ability of Mouse Macrophages

Haoxin Shi1, Dong Li2, Qing Shi2

  • 1Endoscopy Room, Department of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China.

Frontiers in Immunology
|January 10, 2022
PubMed

Insights

Three-dimensional (3D) macrophage culture using collagen microcarriers significantly alters cell morphology and reduces angiogenic potential compared to traditional 2D methods. This 3D system offers new insights into macrophage behavior in tissue-like environments.

Area of Science:

  • Cell Biology
  • Biotechnology
  • Tissue Engineering

Background:

  • Macrophages are crucial for angiogenesis, the formation of new blood vessels.
  • Previous research on macrophage angiogenesis primarily utilized 2D cell culture models.
  • The limitations of 2D cultures in mimicking in vivo tissue environments are well-documented.

Purpose of the Study:

  • To establish and evaluate a 3D macrophage culture system using collagen microcarriers.
  • To investigate the impact of 3D culture on macrophage morphology and angiogenic capabilities.
  • To compare the angiogenic potential of macrophages cultured in 3D versus 2D environments.

Main Methods:

  • Development of a 3D macrophage culture system utilizing collagen microcarriers.
  • Morphological and ultrastructural analysis of macrophages using electron microscopy.
  • Assessment of angiogenic potential via in vitro tube formation assays and in vivo chick embryo chorioallantoic membrane assays.
  • Whole-transcriptome sequencing to identify differential gene expression.

Main Results:

  • Macrophages in 3D culture exhibited distinct morphology and arrangement compared to 2D cultures.
  • 3D-cultured macrophages demonstrated significantly reduced angiogenic capacity in both tube formation and chorioallantoic membrane assays.
  • Whole-transcriptome analysis revealed differential expression in nearly 40% of genes, including downregulation of key angiogenic factors like VEGFA and ANG2.
  • Expression of genes within major angiogenic pathways was notably decreased in 3D-cultured macrophages.

Conclusions:

  • The 3D macrophage culture system provides a more physiologically relevant model for studying macrophage-mediated angiogenesis.
  • Macrophages cultured in 3D exhibit suppressed angiogenic potential compared to those in 2D culture.
  • These findings enhance understanding of macrophage behavior in tissue contexts and offer novel research methodologies.