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Background <p>One promising strategy to generate humanized organs is through embryo complementation by injecting human pluripotent stem cells (PSCs) into gene-edited porcine embryos. This strategy is predicated on how human cells adapt to a porcine environment, which has a body temperature of 38.5&#xa0;°C, much higher than that of the human body.</p> Results <p>Here, we present an <i>in vitro</i> model to address this problem by coculturing human and porcine induced PSCs at 38.5&#xa0;°C and inducing them to generate cardiomyocytes. We show that co-cultured human cells can differentiate into myocardial features with the help of porcine cells at an enhanced differentiation rate. Mechanistically, we show that co-cultured human cells respond to elevated temperature by activating a stress response with the PI3K-Akt-mTOR signaling pathway activated. Moreover, a model mimicking embryo complementation by knocking out <i>MYH6</i> in pig PSCs reveals the potential risk of porcine cells leaking into human-derived tissues.</p> Conclusions <p>Together, our studies present a novel model system to evaluate human and porcine cell co-differentiation that may guide the planning of <i>in vivo</i> experiments.</p>

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In vitro mimicking of humanized cardiogenesis under porcine condition

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月28日

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  • Jiajun Li,
  • Changjiang Xu,
  • Bingbo Shi,
  • Yawen Lyu,
  • Zejie Lin,
  • Wei Shi,
  • Jiachen Xu,
  • Xinle Zou,
  • Xiaomin Wang,
  • Hanqing Zhao,
  • Chengchen Zhao,
  • Duanqing Pei

摘要

Background

One promising strategy to generate humanized organs is through embryo complementation by injecting human pluripotent stem cells (PSCs) into gene-edited porcine embryos. This strategy is predicated on how human cells adapt to a porcine environment, which has a body temperature of 38.5 °C, much higher than that of the human body.

Results

Here, we present an in vitro model to address this problem by coculturing human and porcine induced PSCs at 38.5 °C and inducing them to generate cardiomyocytes. We show that co-cultured human cells can differentiate into myocardial features with the help of porcine cells at an enhanced differentiation rate. Mechanistically, we show that co-cultured human cells respond to elevated temperature by activating a stress response with the PI3K-Akt-mTOR signaling pathway activated. Moreover, a model mimicking embryo complementation by knocking out MYH6 in pig PSCs reveals the potential risk of porcine cells leaking into human-derived tissues.

Conclusions

Together, our studies present a novel model system to evaluate human and porcine cell co-differentiation that may guide the planning of in vivo experiments.