Stem Cells: Generating Lung Cells from PluriPotent Stem Cells

Hans-Willem Snoeck MD, PhD Columbia University Medical Interview with:
Hans-Willem Snoeck MD, PhD
Columbia University Medical Center What are the main findings of the study?

Dr. Snoeck: We were, for the first time, able to differentiate human embryonic stem cells and induced pluripotent stem cells into at least 6 different types of lung and airway epithelial cells. Furthermore, we could demonstrate function of surfactant-producing type II alveolar epithelial cells, and the lung progenitors we generated could generate airway after transplantation under the kidney capsule of immunodeficient mice. Were any of the findings unexpected?

Dr. Snoeck: Differentiation of ES and iPS cells into various cell types of other organs has been relatively successful. Differentiation into lung and airway has been very challenging. We used paradigms from mouse lung development as a guide to differentiation of human stem cells. We also found however that certain signaling pathways required for lung development in the mouse appear redundant in the human system. On the other hand, manipulation of other signaling pathways was essential for human differentiation, while studies in mouse development have not shown evidence for this requirement. What should clinicians and patients take away from your report?

Dr. Snoeck: It will now be possible to model at least some human lung diseases in the laboratory. This will then hopefully lead to strategies to screen for drugs that might treat these diseases. One example is idiopathic lung fibrosis, a disease where the aforementioned type II alveolar epithelial cells are believed to play a major role, but of which the pathogenesis or disease mechanism is not understood. This disease yearly kills 40,000 people in the US, and there is no curative treatment, except for lung transplantation, which carries a high mortality from transplant-related complications.

In addition, this work may allow the development of autologous (the patient’s own) lungs for transplantation. This approach involves harvesting lungs from donors, removing all of the donor’s cells, and replacing those with stem cells derived from the patient. This would alleviate rejection problems. This application is still far away, but this work is a first and critical step in this direction.

Finally, this work will shed light on human lung development, and on a number of congenital diseases affecting lung and airways. Examples are tracheo-esophagal fistulas and tracheal atresia. What recommendations do you have for future research as a result of this study?

Dr. Snoeck: Future research should focus on disease modeling and drug discovery, and on strategies to seed lung scaffolds with iPS-derived lung and airway epithelial cells. Questions that will arise in this area are, for example: how do we generate the adult stem cells that endow a lung with regenerative capacity after damage, how will cells home to their correct location in the lung, and how will we ensure that cilia will coordinately beat in the correct direction to allow removal of mucus and debris from the lung, and how can we scale up this system to generate sufficient numbers of cells for a human lung. Furthermore, we also need to determine to what extent the cells we generated are fully mature (in an adult as opposed to a late fetal stage of development), and how we can mature these further if needed.


Efficient generation of airway and lung epithelial cells from human pluripotent stem cells 
Sarah X L Huang,¬† Mohammad Naimul Islam, John O’Neill, Zheng Hu, Yong-Guang Yang, Ya-Wen Chen,Melanie Mumau,Michael D Green, Gordana Vunjak-Novakovic, Jahar Bhattacharya & Hans-Willem Snoeck
Nature Biotechnology (2013)doi:10.1038/nbt.2754
Received 14 August 2013 Accepted 30 October 2013 Published online 01 December 2013