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Development of a Novel Approach to Regenerate Functional Lungs

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Technical Report,01 May 2017,28 Feb 2019

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Columbia University Medical Center New York United States

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Millions of people suffer from incurable refractory lung diseases. Currently, the only viable option for patients with end-stage pulmonary disease is lung transplantation. The discovery and development of novel treatments for refractory pulmonary disease therapies is relevant to public health, and to a few listed PRMRP Topics. To address this challenge, the main goal of this project was to regenerate functional lungs in vivo in rodents through a Blastocyst Complementation BC approach Aim1, and in utero mediated progenitor transplantation as a contingency approach Aim2. In this regard, we successfully generated functional lungs in mice via blastocyst complementation 100 percent accomplishment. We injected normal donor pluripotent stem cells PSCs labeled by Enhanced Green fluorescent proteins GFP into recipient blastocysts harboring a lung agenesis phenotype. To generate a vacant organ niche specifically in the respiratory system, we utilized a novel approach, Conditional Blastocyst Complementation CBC via Fgfr2 genetic manipulation in the host embryos to avoid an undesired phenotype following injection of PSCs. To the best of our knowledge, we are the first to establish an approach for regeneration of fully functional lungs through CBC. We also established a method for efficient induction of authentic pluripotent stem cells PSCs that supported efficient generation of fully functional lungs. Using our authentic pluripotent stem cells PSCs-enriched culture condition, we rescued the lung agenesis phenotype of genetically deficient hosts via CBC. Notably, these pups survived throughout adulthood with normal lung function.

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  • Medicine and Medical Research

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