Researchers at Phoenix Children's First in the World to Produce Mouse Lungs in Rats

Innovative research brings the field a step closer to creating human lungs using large animals as bioreactors

PHOENIX, March 25, 2024 /PRNewswire/ -- Research conducted at the Phoenix Children's Research Institute at the University of Arizona College of Medicine — Phoenix reports the successful generation of a mouse lung in a rat, according to a paper published in the American Journal of Respiratory and Critical Care Medicine.

"By using a combination of genome editing and blastocyst complementation – a process of injecting murine embryonic stem cells into blastocyst-stage embryos in rats – our research team successfully produced mouse lungs in rats, which is a significant step toward the development of future generations of human lungs," said Vlad Kalinichenko, MD, PhD, internationally renowned lung development and regeneration researcher and director of the Phoenix Children's Research Institute at the University of Arizona College of Medicine – Phoenix. "This is the first time this type of lung generation has been accomplished in the world and it sets the groundwork for new medical advancements and treatments of lung diseases in children and, likely in adults."

This pioneering study "CRISPR/Cas9 Genome Editing Allows Generation of the Mouse Lung in a Rat," focuses on finding an innovative solution for babies born with chronic lung diseases caused by either prematurity or severe genetic conditions. The team of embryologists and pulmonary biologists was led by Bingqiang Wen, PhD, Assistant Professor of Child Health at the University of Arizona College of Medicine – Phoenix, the first author of the manuscript.

"Pediatric patients who have severe forms of lung disease associated with respiratory failure often need transplantable lung tissues and our study proves generating transplantable lungs from stem cells using large animals as bioreactors is possible. It's a groundbreaking finding we hope will save lives in the future," said Dr. Kalinichenko.

Prior to this discovery, the bioengineering and embryonic stem cell (ESC) technology was limited to developing lung tissues consisting of a mixture of donor and recipient cells. These cells, whose origin is a mixture of donor and recipient cells, frequently can be rejected by activation of the recipient's immune response after lung transplantation. The critical differentiating factor with this study is researchers incorporated CRISPR-Cas9, a unique genome editing technology that allows researchers to change genomes by altering sections of the DNA sequence. Modifications of rat embryos by CRISPR-Cas9 allowed the formation of lung tissues consisting of almost all mouse lung cells.

This is one of many recent accolades for the Phoenix Children's Research Institute. Last month, Dr. Kalinichenko was awarded a $3 million grant to support new treatment methods for lung disease in premature infants, and late last year the Institute appointed a renowned scientist focused on pioneering effective treatments for pediatric cancers and a leading researcher in osteogenesis imperfecta.

The Phoenix Children's Research Institute at the University of Arizona College of Medicine –Phoenix launched in May 2023, formalizing a longstanding research collaboration between the health system and the University of Arizona College of Medicine – Phoenix. The Research Institute includes more than 700 active studies, 640 research investigators and 90 research staff members including research scientists, associates, biostatisticians, pharmacists, nurses and coordinators. Scientists engage in research across multiple clinical disciplines including cancer, neurology, cardiology, pulmonology and more.

About Phoenix Children's
Phoenix Children's is one of the nation's largest pediatric health systems. It comprises Phoenix Children's Hospital – Thomas Campus, Phoenix Children's Hospital – East Valley Campus, Phoenix Children's – Avondale Campus, Phoenix Children's – Arrowhead Campus, four pediatric specialty and urgent care centers, 12 community pediatric practices, 20 outpatient clinics, two ambulatory surgery centers and seven community-service outpatient clinics throughout the state of Arizona. The system provides world-class inpatient, outpatient, trauma, emergency and urgent care and has been serving children and families for 40 years. Phoenix Children's Care Network includes more than 1,175 pediatric primary care providers and specialists who deliver care across more than 75 subspecialties. Alongside our colleagues, collaborators and communities, we're elevating pediatric care, education and innovation, so we can all grow healthier together. For more information, visit phoenixchildrens.org.

SOURCE Phoenix Children's