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Scientists create rat

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Chronic obstructive pulmonary disease (COPD) is a severe lung condition that ranks as the third most common cause of death globally. It causes lasting and incurable damage to the lungs, and the only potential cure is a lung transplant. 

Scientists create rat

However, that's a problem because finding suitable lung donors is hard.

To overcome this challenge, scientists are making progress in regenerative medicine and are working to develop artificial lungs from pluripotent stem cells (PSCs) using interspecies animal models.

How did they do it?

Pluripotent stem cells can undergo self-renewal and give rise to all cells of the body's tissues. To test and develop these artificial lungs, researchers from the Nara Institute of Science and Technology (NAIST) in Japan use animal models that mix different species.

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The researchers have combined PSCs and embryonic stem cells (ESCs) using a technique called blastocyst complementation. It's like mixing and matching these cells between different species. 

For example, they can take PSCs or ESCs from one type of animal and put them into the early development stage of another animal missing some of its organs. This creates interspecies chimeric animals, which are animals made up of cells from different species.

Scientists have successfully created the pancreas, heart, and kidney using this technique. However, they haven't quite figured it out when it comes to lungs. Making functional lungs using this method still poses a challenge.

NAIST scientists have figured out how to assemble the right pieces to make animal lungs. The reverse-blastocyst complementation (rBC) method injected mutant ESCs with lung development issues into normal embryos. 

Their research was centered around understanding the significance of a protein called fibroblast growth factor 10 (Fgf10) and how it interacts with a specific form of the Fgf receptor, namely isoform IIIb of Fgf receptor 2 (Fgfr2b), during the development of the lungs.

Using the tetraploid-based organ complementation (TOC) method, they successfully created rat-derived lungs in mouse embryos deficient in Fgf2b without creating a mutant mouse. This research aimed to find an alternative solution to the shortage of donor lungs and improve the chances of treating COPD.

"We believe that our study makes an important contribution to the literature by presenting a faster and more efficient method of exploring blastocyst complementation," said Shunsuke Yuri, co-author of the study.

"These novel results can significantly advance the progress toward developing in-vivo chimeric lungs of transplantation, which could transform the practical application of regenerative medicine," added Yuri.

The study led by Yuri and Ayako Isotani from NAIST was published in development on January 5.

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