Inhale, exhale, in vitro: generating epithelial iPSCs
A new study details findings that provide an alternative way to study human lung regeneration.
A team of researchers from the Boston Medical Center (BMC; MA, USA) and Boston University (BU; MA, USA) have developed a method using pluripotent stem cells (iPSCs) to generate human alveolar epithelial type I cells (AT1s). The model developed in this study will help researchers comprehensively deepen their understanding of human lung regeneration.
Pulmonary diseases such as pulmonary fibrosis, acute respiratory distress syndrome and chronic obstructive pulmonary disease (COPD) affect millions worldwide, and yet lack sufficient effective treatment options. COPD commonly affects middle-aged or older adults, typically after an infection, exposure to toxins, e.g. those found in inhaled smoke, or due to rare genetic conditions that make the lungs more susceptible to injury. This damage to the airways or other parts of the lung blocks airflow, leading to the progression of COPD and resulting in emphysema if the damage spreads to the alveolar sacs, and chronic bronchitis as a result of long term inflammation of the airways. This irreversible damage causes difficulty breathing due to interruption of the gas exchange.
Passive gas exchange takes place at the surface of the alveolus, which are comprised of alveolar sacs, part of the distal lung lined with AT1 cells. These cells are integral to the maintenance of the permeability barrier of the alveolar membrane and have been identified in previous studies to have the potential to develop regenerative therapies for pulmonary diseases.
Both isolating AT1 cells and maintaining them in cell culture have proven challenging in the past, limiting their utility and our ability to further investigate these cells.
In order to address this limitation, the team of researchers set out to engineer a human in vitro AT1 model system through direct differentiation of iPSC. By replicating their natural development from iPSCs, valuable insights can be gathered regarding the development and characteristics of the cells, identifying mechanisms that could be critical in lung regeneration.
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The resulting cells expressed a molecular, morphologic and functional phenotype similar to human AT1 cells. Additionally, the engineered human in vitro AT1 model cells included the ability to form a flat epithelial barrier – presenting extracellular matrix molecules and secreted ligands characteristic of the cells.
“Uncovering the ability to generate human AT1s, and similar cell types, from iPSCs, has expanded our knowledge of biological processes and can significantly improve disease understanding and management,” said Darrell Kotton (BU and BMC).
This study marks a significant step forward in understanding human lung regeneration, pivoting the landscape for improved treatments and therapies for pulmonary diseases.
