New immune-blocking strategy improves interspecies organ generation

Researchers at the Institute of Science Tokyo and Stanford University have discovered a natural immune process called xenophagocytosis that limits the generation of organs from different species. By studying mouse-rat chimeric embryos, they found that embryonic macrophages actively engulf living donor cells from another species when they are placed in a foreign environment.

This process is triggered by the exposure of phosphatidylserine, an "eat-me" signal, on the donor cells' surface. To block this response, the researchers developed three strategies: reducing the host's ability to eliminate donor cells by depleting macrophages or disrupting the Axl receptor, engineering donor cells to express a "don't eat-me" signal (CD47), and increasing the activity of a protein that prevents phosphatidylserine from appearing on the cell surface.

These approaches significantly improved donor cell survival and the generation of rat pancreas in mice, bringing researchers closer to producing transplantable human organs in animals.