Lung bioengineering: physical stimuli and stem/progenitor cell biology interplay towards biofabricating a functional organ.

Paula N. Nonaka,Vinicius R. Oliveira,Ramon Farré,Juan J. Uriarte,Daniel Navajas,Noelia Campillo

doi:10.1186/s12931-016-0477-6

Abstract

A current approach to obtain bioengineered lungs as a future alternative for transplantation is based on seeding stem cells on decellularized lung scaffolds. A fundamental question to be solved in this approach is how to drive stem cell differentiation onto the different lung cell phenotypes. Whereas the use of soluble factors as agents to modulate the fate of stem cells was established from an early stage of the research with this type of cells, it took longer to recognize that the physical microenvironment locally sensed by stem cells (e.g. substrate stiffness, 3D architecture, cyclic stretch, shear stress, air-liquid interface, oxygenation gradient) also contributes to their differentiation. The potential role played by physical stimuli would be particularly relevant in lung bioengineering since cells within the organ are physiologically subjected to two main stimuli required to facilitate efficient gas exchange: air ventilation and blood perfusion across the organ. The present review focuses on describing how the cell mechanical microenvironment can modulate stem cell differentiation and how these stimuli could be incorporated into lung bioreactors for optimizing organ bioengineering.

Highlights

Significant respiratory diseases such as chronic pulmonary obstruction, emphysema, idiopathic pulmonary fibrosis, primary pulmonary arterial hypertension, interstitial lung disease, cystic fibrosis and α-1-antitrypsin deficiency result in irreversible structural lung damage, with lung transplantation as the only therapeutic indication when the disease reaches an advanced progression [1]
The research experience currently available using undifferentiated cells for lung bioengineering indicates that the decellularized organ scaffold would play a fundamental role in modulating important stem cell processes of homing and differentiation, and specially in modulating the secretion of required extracellular matrix (ECM) components which would contribute to tissue reconstruction [20]
As different organs/tissues are subjected to particular biophysical stimuli during normal function, it is reasonable to expect that physiological conditions could promote stem cell differentiation towards specific phenotypes in vitro

Summary

Introduction

Significant respiratory diseases such as chronic pulmonary obstruction, emphysema, idiopathic pulmonary fibrosis, primary pulmonary arterial hypertension, interstitial lung disease, cystic fibrosis and α-1-antitrypsin deficiency result in irreversible structural lung damage, with lung transplantation as the only therapeutic indication when the disease reaches an advanced progression [1]. This short review aims to address the topic of lung bioengineering, focusing on the potential differentiation effects of the mechanical stimuli sensed by stem cells seeded in decellularized organ scaffolds.

Results

Conclusion