Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera development
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Updated: Jun 4, 2025
An Immunological Model for Heterotopic Heart and Cardiac Muscle Cell Transplantation in Rats
Published on: May 8, 2020
Shunsuke Yuri1,2, Norie Arisawa1, Kohei Kitamuro1
1Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan.
Abstract:
The use of pluripotent stem cells (PSCs) to generate functional organs via blastocyst complementation is a cutting-edge strategy in regenerative medicine. However, existing models that use this method for heart generation do not meet expectations owing to the complexity of heart development. Here, we investigated a Mesp1/2 deficient mouse model, which is characterized by abnormalities in the cardiac mesodermal cells. The injection of either mouse or rat PSCs into Mesp1/2 deficient mouse blastocysts led to successful heart generation. In chimeras, the resulting hearts were predominantly composed of rat cells; however, their functionality was limited to the embryonic developmental stage on day 12.5. These results present the functional limitation of the xenogeneic heart, which poses a significant challenge to the development in mouse-rat chimeras.
