Researchers at Boston University School of Medicine (BUSM) and Boston Medical Center (BMC) have derived a population of pure lung progenitor cells in vitro that successfully mimic the developmental milestones of lung tissue formation.
The research, published in the journal Cell Stem Cell, identifies factors necessary for embryonic stem (ES) cells to differentiate into lung progenitor cells and provides key information about how the tissue engineering technology can be used to develop new gene and cell-based therapies to treat lung diseases. The findings represent years of research dedicated to identifying how to generate an unlimited source of lung progenitor cells in vitro from ES cells.
Since ES cells resemble the early developing embryo, the researchers studied normal lung in the developing embryo. They used this knowledge as a roadmap to induce the same sequence of developmental milestones in ES cells in culture.
Previous research shows that progenitor cells from the embryo’s gut tube (called endoderm) give rise to the lungs, thyroid, pancreas, gastrointestinal tract and other organs. This led the researchers to focus on that time of development in order to identify what factors are responsible for how the cells differentiate.
The ES cells were engineered to include a fluorescent tag that glowed at the moment lung cells were generated from ES cells in culture. Using this approach, the researchers differentiated the ES cells into gut tube endoderm and then identified growth factors that induced lung lineages. Ultimately, 160 lung progenitors could be generated per starting stem cell and these progenitors could be purified using the fluorescent tag that glowed only once the cells had become lung cells.
To demonstrate that the cells purified by the investigators were lung progenitors, the research team studied the global gene expression profiles of the cells they derived and placed the cells into a three-dimensional lung scaffold. The cells grew and multiplied, forming two types of lung cells that normally coat the air sacs of the lungs.
The findings indicate that this technology can be used to grow new primordial lung progenitors to study human disease in vitro, which could lead to novel therapies to treat patients with end stage lung disease, such as emphysema and Cystic Fibrosis.
“The ability to generate a supply of progenitor cells with the potential to differentiate into lung cells will be a huge boon to several research fields,” said James Kiley, PhD, director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute, which funded the study. “It lays the groundwork for studying the mechanisms and programming of cells during lung development, which, in turn, will help develop new treatments.”
Source: Boston University School of Medicine