Yuri Shunsuke, Arisawa Norie, Kitamuro Kohei, Isotani Ayako
Division 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.
iScience. 2024 Nov 18;27(12):111414. doi: 10.1016/j.isci.2024.111414. eCollection 2024 Dec 20.
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.
利用多能干细胞（PSC）通过囊胚互补生成功能性器官是再生医学中的一项前沿策略。然而，由于心脏发育的复杂性，现有的使用这种方法生成心脏的模型并未达到预期。在此，我们研究了一种Mesp1/2缺陷小鼠模型，其特征是心脏中胚层细胞存在异常。将小鼠或大鼠的PSC注射到Mesp1/2缺陷小鼠囊胚中可成功生成心脏。在嵌合体中，生成的心脏主要由大鼠细胞组成；然而，它们的功能仅限于胚胎发育第12.5天的阶段。这些结果揭示了异种心脏的功能局限性，这对小鼠 - 大鼠嵌合体的发育构成了重大挑战。
