Scientists Crack the "Xenogeneic Barrier", Offering a New Path for Growing Human Organs in Animals
Release time:
2025-12-19
If one day doctors can grow suitable human organs inside animals, the global shortage of organs may find a turning point. The key to realizing this vision lies in overcoming the "xenogeneic barrier"—enabling human pluripotent stem cells to successfully integrate into other mammalian embryos and form cross-species chimeras. Recently, a breakthrough achievement addressing this challenge was published in the world-renowned academic journal Cell, marking a significant advancement in the field of regenerative medicine.
For a long time, human cells have often been excluded and struggled to survive in animal embryos due to the "xenogeneic barrier." The mainstream strategy in the past involved genetically engineering human cells to enhance their anti-apoptotic capabilities, but this approach carries potential safety risks such as carcinogenesis. How can this barrier be overcome more safely? A collaborative team led by the University of Texas Southwestern Medical Center and BGI Research used mice as a model to tackle this issue and achieved a critical breakthrough.
The study found that when human and mouse pluripotent stem cells are co-cultured, some RNA from human cells enters mouse cells, which recognize it as an "invader," subsequently activating the RNA innate immune pathway to eliminate the human cells. However, when the key molecules RIG-I and MAVS in this pathway were knocked out in mouse cells, the survival rate and embryonic chimerism of human cells significantly improved without the need for genetic modification. This indicates that RNA innate immunity is an overlooked "xenogeneic barrier," and modifying the host animal can effectively dismantle it.
Further research revealed that the entry of human RNA into mouse cells relies on direct cell contact—the two types of cells form slender "tunneling nanotubes" (TNTs), through which RNA triggers the mouse immune response. When drugs were used to sever these nanotubes, the amount of human-derived RNA in mouse cells decreased, and the survival conditions of human cells improved accordingly.
The research team noted that this approach aligns more closely with the safety and controllability requirements of regenerative medicine than directly modifying human cells. In the future, if strategies such as blocking RNA immunity and matching developmental rhythms can be combined, the safe and efficient cultivation of human organs in animals may gradually become a reality.
From cracking the "xenogeneic barrier" to exploring safer organ cultivation pathways, this study published in Cell opens up new possibilities for addressing the global organ shortage. Although RNA innate immunity is just one component of the barrier, this breakthrough has laid a solid foundation for the dream of growing human organs in animals, bringing the future of regenerative medicine one step closer.
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