# Matrix-Guided Vascular-like Cord Formation by MRC-5 Lung Fibroblasts: Evidence of Structural and Transcriptional Plasticity

## TL;DR

This study shows that lung fibroblasts can form vascular-like structures in a 3D environment, suggesting their potential for tissue engineering.

## Contribution

The study demonstrates structural and transcriptional plasticity of MRC-5 fibroblasts in forming vascular-like cords in Matrigel.

## Key findings

- MRC-5 cells self-organized into cord-like networks resembling early vascular patterning.
- Transcriptomic analysis showed upregulation of genes related to nervous system development and synaptic signaling.
- At higher densities, cells formed spheroid-like aggregates and invaded the hydrogel.

## Abstract

The role of mesenchymal-to-endothelial transition in the angiogenic response remains controversial. In this study, we investigated whether human fetal lung fibroblasts (MRC-5 cells) exhibit morphological plasticity in a biomimetic extracellular matrix environment. To this end, MRC-5 cells were first cultured on and within Matrigel hydrogel and then studied with tube formation assays, confocal/fluorescence microscopy, invasion assays, and transcriptomic profiling. In addition, quantitative assessment for cord formation and gene expression was conducted via qPCR and RNA sequencing. In this study, MRC-5 cells quickly self-organized into cord-like networks, resembling early stages of vascular patterning, and at higher densities, invaded the hydrogel and formed spheroid-like aggregates. Transcriptomic analysis revealed upregulation of genes related to nervous system development and synaptic signaling in Matrigel-grown MRC-5 cultures. Collectively, these findings suggest that MRC-5 fibroblasts display structural and transcriptional plasticity in 3D Matrigel cultures, forming vascular-like cords that are more likely to resemble early developmental morphologies or neuroectodermal-like transcriptional signatures than definitive endothelial structures. This work underscores the potential of fibroblasts as an alternative cell source for vascular tissue engineering and highlights a strategy to overcome current limitations in autologous endothelial cell availability for regenerative applications.