Stem cells form human mini-lung organoids

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Stem cells form human mini-lung organoids

stem cell organoid

Scientists, led by the University of Michigan Medical School, coax stem cells to form mini lungs, 3-D structures that mimic human lungs and survived in the lab for 100 days. (Source: University of Michigan Health System)

Organoids are in vitro organ models generated by the self-assembly of cells (likely to be stem cells or induced pluripotent stem cells) into small tissues that replicate some of the 3-dimensional (3-D) cellular and structural complexity of the in vivo tissue/organ. The growing interest in generating organoids as research and testing models was reviewed in this recent article in Science, “Organogenesis in a dish: modeling development and disease using organoid technologies.”

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

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