Associate profesor National Center for Geriatrics and Gerontology Obu-Shi, Aichi, Japan
Abstract: Regenerative medicine serves as a promising tool to address the shortage of organs for transplantation. However, constructing organs in vitro remains challenging due to the complex three-dimensional structures and the diverse cell types required. Interspecies blastocyst complementation using chimeric animals has garnered attention as a potential approach to generate complex organs in animals, thus helping to overcome the issue of organ shortage.
Here, we report the generation of rat lungs and hearts in a mouse body via interspecies blastocyst complementation. For lungs, rat lung development was observed up to the P0 stage. However, the rat cells within the generated lungs unexpectedly retained their species-specific developmental timing in the mouse body, rendering the lungs non-functional after birth. Similarly, we successfully generated hearts using rat cell complementation in a heart-deficient mouse model, but the rat heart in the mouse only functioned until embryonic day 14.5 (E14.5).
These findings highlight the functional limitations of xenogeneic lungs and hearts, presenting significant challenges in the development of mouse–rat chimeras. To address these issues, new strategies must be developed to overcome the challenges associated with interspecies blastocyst complementation.
Funding Source: Japan Society for the Promotion of Science KAKENHI KAC 40th Anniversary Research Grant NOVARTIS Foundation (Japan) for the Promotion of Science Nara Institute of Science and Technology