Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera development

Summary: 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...

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Main Authors: Shunsuke Yuri, Norie Arisawa, Kohei Kitamuro, Ayako Isotani
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004224026397
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author Shunsuke Yuri
Norie Arisawa
Kohei Kitamuro
Ayako Isotani
author_facet Shunsuke Yuri
Norie Arisawa
Kohei Kitamuro
Ayako Isotani
author_sort Shunsuke Yuri
collection DOAJ
description Summary: 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.
format Article
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publishDate 2024-12-01
publisher Elsevier
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spelling doaj-art-c004a2d47a3c41fb94c46ee3c92b9f0e2025-08-20T02:40:14ZengElsevieriScience2589-00422024-12-01271211141410.1016/j.isci.2024.111414Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera developmentShunsuke Yuri0Norie Arisawa1Kohei Kitamuro2Ayako Isotani3Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan; Laboratory of Experimental Animals, Research Institution, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi 474-8511, Japan; Corresponding authorDivision of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, JapanDivision of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, JapanDivision of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan; Life Science Collaboration Center (LiSCo), Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224026397Health sciencescardiovascular medicinebiological sciences
spellingShingle Shunsuke Yuri
Norie Arisawa
Kohei Kitamuro
Ayako Isotani
Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera development
iScience
Health sciences
cardiovascular medicine
biological sciences
title Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera development
title_full Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera development
title_fullStr Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera development
title_full_unstemmed Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera development
title_short Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera development
title_sort blastocyst complementation based rat derived heart generation reveals cardiac anomaly barriers to interspecies chimera development
topic Health sciences
cardiovascular medicine
biological sciences
url http://www.sciencedirect.com/science/article/pii/S2589004224026397
work_keys_str_mv AT shunsukeyuri blastocystcomplementationbasedratderivedheartgenerationrevealscardiacanomalybarrierstointerspecieschimeradevelopment
AT noriearisawa blastocystcomplementationbasedratderivedheartgenerationrevealscardiacanomalybarrierstointerspecieschimeradevelopment
AT koheikitamuro blastocystcomplementationbasedratderivedheartgenerationrevealscardiacanomalybarrierstointerspecieschimeradevelopment
AT ayakoisotani blastocystcomplementationbasedratderivedheartgenerationrevealscardiacanomalybarrierstointerspecieschimeradevelopment