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<p>Existing immunodeficient pig models have demonstrated limited success in supporting robust human haematopoietic engraftment and multilineage differentiation. Here we hypothesize that the targeted deletion of integrin-associated protein (Cd47) in severe combined immunodeficient pigs, with deletions in the X-linked interleukin-2 receptor gamma chain and recombination activating gene 1, would enable long-term haematopoietic engraftment following transplantation with human haematopoietic stem/progenitor cells. In Cd47-deficient pigs, we observed high levels of human haematopoietic chimerism in the blood and spleen, with functional T and B lymphocytes, natural killer and myeloid cells, as well as robust thymopoiesis. Our findings suggest that severe combined immunodeficient pigs with Cd47 deletion represent an improved preclinical model for studying human haematopoiesis, disease mechanisms and therapies, and offer potential as a bioreactor for large-scale production of human immune cells.</p>

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Long-term engraftment of human stem and progenitor cells for large-scale production of functional immune cells in engineered pigs

  • 期刊论文

  • 发表日期：

    2025年5月20日

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  • Zheng Hu,
  • Jun Zou,
  • Zhengzhu Wang,
  • Kai Xu,
  • Tang Hai,
  • Sheng Zhang,
  • Peipei An,
  • Cong Fu,
  • Shuai Dong,
  • Yanan Lv,
  • Jilong Ren,
  • Zhiqiang Han,
  • Chongyang Li,
  • Jing Wang,
  • Qingwei Wang,
  • Renren Sun,
  • Long Su,
  • Hanjing Zuo,
  • Qinghao Ding,
  • Huimin Tian,
  • Xinlan An,
  • Yanhui Zhai,
  • Dawei Yu,
  • Chang Shu,
  • Jin He,
  • Liguang Sun,
  • Tianmeng Sun,
  • Xiangpeng Dai,
  • Ziyi Li,
  • Wei Li,
  • Qi Zhou,
  • Yong-Guang Yang

摘要

Existing immunodeficient pig models have demonstrated limited success in supporting robust human haematopoietic engraftment and multilineage differentiation. Here we hypothesize that the targeted deletion of integrin-associated protein (Cd47) in severe combined immunodeficient pigs, with deletions in the X-linked interleukin-2 receptor gamma chain and recombination activating gene 1, would enable long-term haematopoietic engraftment following transplantation with human haematopoietic stem/progenitor cells. In Cd47-deficient pigs, we observed high levels of human haematopoietic chimerism in the blood and spleen, with functional T and B lymphocytes, natural killer and myeloid cells, as well as robust thymopoiesis. Our findings suggest that severe combined immunodeficient pigs with Cd47 deletion represent an improved preclinical model for studying human haematopoiesis, disease mechanisms and therapies, and offer potential as a bioreactor for large-scale production of human immune cells.