Spatial distribution and density of fibroblasts determine angiogenic response of endothelial cells.
5 affiliations
- 1Soft Biomatter Laboratory, Department of Materials Science and Engineering, University of Virginia, Charlottesville, VA 22904 USA.
- 2Department of Mechanical and Aerospace Engineering, University of Virginia, Charlottesville, VA 22904 USA.
- 3Department of Chemical Engineering, University of Virginia, Charlottesville, VA 22904 USA.
- 4Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22904 USA.
- 5Department of Chemistry, University of Virginia, Charlottesville, VA 22904 USA.
Abstract
Fibroblasts play indispensable roles in orchestrating revascularization and angiogenesis of endothelial cells. However, the specific conditions under which the influence of fibroblasts becomes important in modulating angiogenic formation remain to be determined. Here, we extend a previously established microfluidic co-culture system to enable precise manipulation of the density of human lung fibroblasts (HLF) and their distance to human umbilical vein endothelial cells (HUVECs) in a wide range within fibrin hydrogels. Using live cell imaging and image analysis, we quantify the effects of fibroblast density, HLF- HUVEC cell-cell distance, and culturing time on cell migration, morphology, microvasculature, and endothelial sprouting. We find that, within the system and parameter range explored here, for fibroblasts to have a significant positive impact in the angiogenesis of endothelial cells, the fibroblast density should be no less than ~3×10⁶ cells/ml and the cell-cell distance should be no greater than ~2 mm. The experimental findings can be captured by a minimal model accounting for the concentration profile of pro-angiogenic factors secreted by fibroblasts. Our results provide insights into the remodeling of vasculature and the guidance for engineering vascularized tissue mimics.Supplementary information
The online version contains supplementary material available at https://doi.org/10.1007/s10404-026-02939-3.
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BibTeX
@article{zhang2026spatial,
title = {{Spatial distribution and density of fibroblasts determine angiogenic response of endothelial cells.}},
author = {Pu Zhang and Melur K Ramasubramanian and Li-Heng Cai},
journal = {Microfluidics and nanofluidics},
year = {2026},
month = oct,
doi = {10.1007/s10404-026-02939-3},
url = {https://europepmc.org/article/MED/42889306},
note = {CC BY},
}
RIS
TY - JOUR
TI - Spatial distribution and density of fibroblasts determine angiogenic response of endothelial cells.
AU - Pu Zhang
AU - Melur K Ramasubramanian
AU - Li-Heng Cai
PY - 2026
DA - 2026/10/14
JO - Microfluidics and nanofluidics
DO - 10.1007/s10404-026-02939-3
UR - https://europepmc.org/article/MED/42889306
AB - Fibroblasts play indispensable roles in orchestrating revascularization and angiogenesis of endothelial cells. However, the specific conditions under which the influence of fibroblasts becomes important in modulating angiogenic formation remain to be determined. Here, we extend a previously established microfluidic co-culture system to enable precise manipulation of the density of human lung fibroblasts (HLF) and their distance to human umbilical vein endothelial cells (HUVECs) in a wide range within fibrin hydrogels. Using live cell imaging and image analysis, we quantify the effects of fibroblast density, HLF- HUVEC cell-cell distance, and culturing time on cell migration, morphology, microvasculature, and endothelial sprouting. We find that, within the system and parameter range explored here, for fibroblasts to have a significant positive impact in the angiogenesis of endothelial cells, the fibroblast density should be no less than ~3×10⁶ cells/ml and the cell-cell distance should be no greater than ~2 mm. The experimental findings can be captured by a minimal model accounting for the concentration profile of pro-angiogenic factors secreted by fibroblasts. Our results provide insights into the remodeling of vasculature and the guidance for engineering vascularized tissue mimics.Supplementary information The online version contains supplementary material available at https://doi.org/10.1007/s10404-026-02939-3.
SN - 1613-4982
ER -