Human Airway Basal Stem Cells Generated from IPSCs for the First Time

Human Airway Basal Stem Cells Generated from IPSCs for the First Time

A team of researchers from the Center for Regenerative Medicine at Boston Medical Center (CReM), Boston University, and University of Texas Health Science Center at Houston has, for the first time, generated airway basal stem cells by reprogramming induced pluripotent stem cells. The cells could be used for research into diseases that affect the airways such as cystic fibrosis, asthma, and potentially even COVID-19, and could also be used in personalized treatments for patients with diseases of the airways.

Airway basal stem cells are stem cells that can differentiate into any cells of the airways. Airway basal stem cells could, for instance, repair damage to the respiratory epithelium – the cells that line most of the respiratory tract, including the respiratory mucosa which moistens and protects the airways and is damaged by several diseases of the airways.

The researchers developed a technique to generate and purify large quantities of airway basal stem cells which could be used to create models of diseases which could then be used for the development of drugs or even to regenerate the airways in vivo.

Induced pluripotent stem cells were created with a genetic sequence that encoded a fluorescent protein which allowed the researchers to track airway basal stem cells. After studying previous research on the formation of basal stem cells in the airways, the researchers recreated conditions similar to those present during lung development and successfully generated airway basal stem cells that were very similar in appearance to those found in the airways with the same capabilities to create any airway cells. The fluorescent protein allowed the researchers to identify and purify the cells. The researchers then tested their new cells in vivo in a rodent trachea model and were able to regenerate damaged airway cells.

The researchers also generated airway basal stem cells – termed ibasal cells – from cells harvested from patients with a range of lung diseases and were able to successfully model those diseases in the lab. Those models could be used to study the genetic changes that cause lung diseases and correct changes in new treatments for the diseases.

“We demonstrated the potential of these ibasal cells to model both human development and disease, providing evidence of their capacity to regenerate airway epithelium,” said Finn Hawkins, MB, BCh, principal investigator at CReM and first author of the study. “We expect this will be a significant breakthrough and will contribute to new insights and treatment options for airway diseases, as our results have overcome several important hurdles currently limiting progress in the field.”

One potential approach would be to harvest cells from a patient with cystic fibrosis, convert those cells into induced pluripotent stem cells, correct the genetic mutation that causes the disease, convert the stem cells to airway basal stem cells, and then reintroduce them to the patient to regenerate the damaged cells of the airways and cure the disease. A similar approach could be used to cure other diseases of the airways.

Under CReM’s Open Source Biology approach to sharing research data, the findings and the cells produced will be freely given to researchers.

You can read more about the study in the paper – Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells – which was recently published in the journal Cell Stem Cell. DOI: 10.1016/j.stem.2020.09.017

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