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The perspective for next-generation lung replacement therapies: functional whole lung generation by blastocyst
Dai Shimizu1,2, Akihiro Miura1,2, Munemasa Mori1
1Columbia Center for Human Development and Division of Pulmonary, Allergy, Critical Care, Department of Medicine, Columbia University Medical Center, New York, New York, USA.
Current Opinion in Organ Transplantation
|August 16, 2024
Summary
Lung blastocyst complementation shows promise for regenerative medicine. Creating functional human lungs via interspecies chimera formation faces challenges in host niche control and interspecies barriers.
Area of Science:
- Regenerative Medicine
- Developmental Biology
- Bioengineering
Background:
- Blastocyst complementation is a novel technique for generating organs.
- Lung replacement therapies are crucial for treating respiratory diseases.
Purpose of the Study:
- To review the prospects of lung blastocyst complementation in clinical settings.
- To summarize studies on generating functional lungs via blastocyst complementation.
- To explore host animal selection for interspecific chimera formation.
Main Methods:
- Gene mutations were used to create vacant lung niches in rodent models.
- Controlling gene mutation lineage improved lung chimerism.
- Interspecific blastocyst complementation identified genes enhancing human-mammal chimera formation.
Main Results:
- Functional lungs have been created using intraspecies blastocyst complementation.
- Interspecific lung generation remains a significant challenge.
- Several genes enhance chimera formation between humans and other mammals.
Conclusions:
- Generating functional interspecific lungs requires addressing host niche control.
- Selecting appropriate host animals is critical for overcoming interspecies barriers.
- Successful interspecies blastocyst complementation could lead to humanized or entire human lungs in large animals.
