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Publication : Incompatibility in cell adhesion constitutes a barrier to interspecies chimerism.

First Author  Ballard E Year  2024
Journal  Cell Stem Cell PubMed ID  39181131
Mgi Jnum  J:353958 Mgi Id  MGI:7717280
Doi  10.1016/j.stem.2024.07.010 Citation  Ballard E, et al. (2024) Incompatibility in cell adhesion constitutes a barrier to interspecies chimerism. Cell Stem Cell
abstractText  Interspecies blastocyst complementation holds great potential to address the global shortage of transplantable organs by growing human organs in animals. However, a major challenge in this approach is the limited chimerism of human cells in evolutionarily distant animal hosts due to various xenogeneic barriers. Here, we reveal that human pluripotent stem cells (PSCs) struggle to adhere to animal PSCs. To overcome this barrier, we developed a synthetic biology strategy that leverages nanobody-antigen interactions to enhance interspecies cell adhesion. We engineered cells to express nanobodies and their corresponding antigens on their outer membranes, significantly improving adhesion between different species' PSCs during in vitro assays and increasing the chimerism of human PSCs in mouse embryos. Studying and manipulating interspecies pluripotent cell adhesion will provide valuable insights into cell interaction dynamics during chimera formation and early embryogenesis.
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