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Developmental Biology
Cocultivo epitelial, mesenquimatal, endotelial e inmunitario derivado de iPSC para modelar la int...
Cocultivo epitelial, mesenquimatal, endotelial e inmunitario derivado de iPSC para modelar la int...
JoVE Journal
Developmental Biology
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JoVE Journal Developmental Biology
iPSC-Derived Epithelial, Mesenchymal, Endothelial, and Immune Cell Co-Culture to Model Airway Barrier Integrity in Lung Health and Disease

Cocultivo epitelial, mesenquimatal, endotelial e inmunitario derivado de iPSC para modelar la integridad de la barrera de las vías respiratorias en la salud y la enfermedad pulmonar

Full Text
2,178 Views
06:27 min
December 6, 2024

DOI: 10.3791/67247-v

Rachael N. McVicar1,2, Emily Smith1,2, Melina Melameka1,2, Anne Bush1,2, Grace Goetz1,2, Gailan Constantino1,2, Matangi Kumar1,2, Elizabeth Kwong1,2, Evan Y. Snyder1,2, Sandra L. Leibel1,2,3

1Sanford Consortium for Regenerative Medicine, 2Sanford Burnham Prebys Medical Discovery Institute, 3Department of Pediatrics,University of California, San Diego School of Medicine

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Overview

This article describes the generation of a complex, multi-cellular airway barrier model composed of induced pluripotent stem cell (iPSC)-derived lung epithelium, mesenchyme, endothelial cells, and macrophages in an air-liquid interface culture. The model aims to better understand human airway remodeling and its response to environmental toxins.

Key Study Components

Area of Science

  • Neuroscience
  • Cell Biology
  • Respiratory Physiology

Background

  • The human airway acts as a barrier against environmental toxins.
  • Toxins can cause airway injury and remodeling, affecting breathing.
  • Modeling the human lung in vitro presents significant challenges.
  • Primary lung samples are difficult to obtain and culture.

Purpose of Study

  • To create a multi-cellular model of the airway barrier.
  • To include various cell types important for airway homeostasis.
  • To facilitate research on airway remodeling and responses to toxins.

Methods Used

  • Generation of iPSC-derived lung epithelial cells.
  • Incorporation of mesenchymal and endothelial cells.
  • Culture of cells in an air-liquid interface.
  • Assessment of model functionality and cellular interactions.

Main Results

  • Successful generation of a complex airway barrier model.
  • Model includes key cell types: epithelial, mesenchymal, endothelial, and macrophages.
  • Demonstrated potential for studying airway responses to environmental factors.
  • Addressed challenges in modeling human lung tissue in vitro.

Conclusions

  • The developed model provides insights into airway remodeling.
  • It serves as a valuable tool for future research on lung health.
  • Potential applications in studying disease mechanisms and therapeutic interventions.

Frequently Asked Questions

What is the significance of the airway barrier model?
The model helps researchers understand how the airway responds to environmental toxins and the mechanisms of airway remodeling.
What types of cells are included in the model?
The model includes induced pluripotent stem cell-derived lung epithelial cells, mesenchymal cells, endothelial cells, and macrophages.
How does this model improve upon previous models?
It incorporates multiple cell types that are crucial for airway homeostasis, providing a more accurate representation of human lung tissue.
What challenges does this research address?
It addresses the difficulties in obtaining and culturing primary lung samples for research purposes.
What are the potential applications of this research?
The findings could lead to better understanding of lung diseases and the development of new therapeutic strategies.

Este artículo describe la generación de un modelo complejo de barrera multicelular de la vía aérea compuesto por epitelio pulmonar derivado de células madre pluripotentes inducidas (iPSC), mesénquima, células endoteliales y macrófagos en un cultivo de interfaz aire-líquido.

Mi investigación se centra en la comprensión de la remodelación de las vías respiratorias humanas. Las vías respiratorias humanas sirven como barrera contra las toxinas ambientales, incluidos los virus, la contaminación del aire y el humo del tabaco. Estas toxinas pueden dañar las vías respiratorias, haciendo que cambien o se remodelen, dificultando la respiración.

El sistema modelo incluye no solo las células epiteliales que forman la barrera, sino también otras células que son importantes en la homeostasis de las vías respiratorias, incluidas las células de los vasos sanguíneos y las células inmunitarias llamadas macrófagos. Los desafíos experimentales actuales incluyen el modelado del pulmón humano en un sistema de modelos in vitro. La obtención de muestras primarias de pulmón es difícil y también son muy difíciles de cultivar.

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