Development of endomyocardial fibrosis model using a cell patterning technique: In vitro interaction of cell coculture of 3T3 fibroblasts and RL-14 cardiomyocytes

PLoS One. 2020 Feb 24;15(2):e0229158. doi: 10.1371/journal.pone.0229158. eCollection 2020.

Abstract

Cardiac functions can be altered by changes in the microstructure of the heart, i.e., remodeling of the cardiac tissue, which may activate pathologies such as hypertrophy, dilation, or cardiac fibrosis. Cardiac fibrosis can develop due to an excessive deposition of extracellular matrix proteins, which are products of the activation of fibroblasts. In this context, the anatomical-histological change may interfere with the functioning of the cardiac tissue, which requires specialized cells for its operation. The purpose of the present study was to determine the cellular interactions and morphological changes in cocultures of 3T3 fibroblasts and RL-14 cardiomyocytes via the generation of a platform an in vitro model. For this purpose, a platform emulating the biological characteristics of endomyocardial fibrosis was generated using a cell patterning technique to study morphological cellular changes in compact and irregular patterns of fibrosis. It was found that cellular patterns emulating the geometrical distributions of endomyocardial fibrosis generated morphological changes after interaction of the RL-14 cardiomyocytes with the 3T3 fibroblasts. Through this study, it was possible to evaluate biological characteristics such as cell proliferation, adhesion, and spatial distribution, which are directly related to the type of emulated endomyocardial fibrosis. This research concluded that fibroblasts inhibited the proliferation of cardiomyocytes via their interaction with specific microarchitectures. This behavior is consistent with the histopathological distribution of cardiac fibrosis; therefore, the platform developed in this research could be useful for the in vitro assessment of cellular microdomains. This would allow for the experimental determination of interactions with drugs, substrates, or biomaterials within the engineering of cardiac tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Adhesion
  • Cell Communication*
  • Cell Line
  • Cell Proliferation
  • Coculture Techniques / methods*
  • Endomyocardial Fibrosis / etiology*
  • Endomyocardial Fibrosis / pathology
  • Fibroblasts / pathology*
  • Humans
  • Mice
  • Models, Biological
  • Myocytes, Cardiac / pathology*

Grants and funding

This research was supported by the Department of Science, Technology and Innovation- COLCIENCIAS, Colombia (project No. 121074455524) and the International Center for Genetic Engineering and Biotechnology–ICGEB, Italy (project No. CRP/COL17-03). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.