Stem cells form human mini-lung organoids
Researchers from the University of Michigan Medical Center and Cincinnati Children’s Hospital Medical Center, sometimes in collaboration with other academic centers, have developed 3-D organoid models for several types of human tissues, including intestinal organoids (Rodansky et al., 2015; Sinagoga and Wells, 2015; Watson et al., 2014; Wells and Spence, 2014; Brugmann and Wells, 2013; Spence et al., 2011), and gastric organoids (McCracken et al., 2014).
Some of these same researchers have now developed a new method for generating self-organizing human lung organoids that have survived over 100 days in culture (Dye et al., 2015).
Specific signaling pathways in human induced pluripotent stem cells (iPSCs) were manipulated sequentially to generate the human lung organoids (HLOs).
“Scientists activated two important development pathways that are known to make endoderm form three-dimensional tissue. By inhibiting two other key development pathways at the same time, the endoderm became tissue that resembles the early lung found in embryos….to make these structures expand and develop into lung tissue…the team exposed the cells to additional proteins that are involved in lung development.”
Their summary best explains the cellular and structural complexity of the model developed.
“HLOs possess both mesenchymal and epithelial lineages, as well as organized proximal airway structures with multiple cell types and surrounded by mesenchyme. HLOs also possess distal epithelial cells that are reminiscent of a bipotent alveolar progenitor cell recently described in mice, which is likely a reflection of the similarities of HLOs to the human fetal lung. We believe that HLOs will be an excellent new human system to model lung differentiation, homeostasis, and disease in vitro.”
Citation to the article discussed here:
Dye, B.R., Hill, D.R., Ferguson, M.A., Tsai, Y-H., Nagy, M.S., Dyal, R., Wells, J.M., Mayhew, C.N., Nattiv, R., Klein, O.D., White, E.S., Deutsch, G.H., & Spence, J.R. (2015, March). In vitro generation of human pluripotent stem cell derived lung organoids. eLife. doi: 10.7554/eLife.05098
Open-access article: http://elifesciences.org/content/4/e05098/article-info
News release: Scientists coax stem cells to form 3-D mini lungs
Posted: April 10, 2015