Developmentally Conserved CDX2 Cells from Human Term Placenta Drive Cardiovascular Regeneration

We report a population of multipotent cells isolated from term human placentas that exhibit clonal expansion, migratory capacity, and a gene expression profile indicating immune privilege. These cells, expressing the developmental regulator CDX2, previously known only for its role in early placentation, differentiate into cardiomyocytes and vascular cells. Building on our prior findings that murine Cdx2 cells improved cardiac function in mice after myocardial infarction (MI), we isolated CDX2⁺ cells from placentas of 180 healthy pregnancies. These human CDX2 cells spontaneously generate cardiac and vascular lineages in vitro, in vivo, and express transcriptomic signatures associated with cardiogenesis, vasculogenesis, immune modulation, and chemotaxis. When administered to NOD/SCID mice after MI, the cells restore cardiac function. Additionally, CDX2 cells can be clonally propagated while retaining cardiovascular differentiation potential. Our findings support the therapeutic potential of placental CDX2 cells as an ethically accessible and regenerative strategy for cardiovascular disease.