Discovery of a multipotent cell type from the term human placenta

We report a unique population of multipotent cells isolated from the term human placenta, for the first time, that can differentiate into cardiomyocytes and vascular cells with clonal proliferative ability, migratory ability, and trancriptomic evidence of immune privilege. Caudal-type homeobox-2 (CDX2) is a conserved factor that regulates trophectoderm formation and placentation during early embryonic development but has not previously been implicated in developmentally conserved regenerative mechanisms. We had earlier reported that Cdx2 lineage cells in the mouse placenta are capable of restoring cardiac function after intravenous delivery in male mice with experimental cardiac injury (myocardial infarction). Here we demonstrate that CDX2-expressing cells are prevalent in the human chorion and are poised for cardiovascular differentiation. We examined the term placentas from 106 healthy patients and showed that isolated CDX2 cells can spontaneously differentiate into cardiomyocytes, functional vascular cells, and retain homing ability in vitro. Functional annotation from transcriptomics analysis supports enhanced cardiogenesis, vasculogenesis, immune modulation, and chemotaxis gene signatures in CDX2 cells. CDX2 cells can be clonally propagated in culture with retention of cardiovascular differentiation. Our data supports further use of this accessible and ethically feasible cell source in the design of therapeutic strategies for cardiovascular disease. ### Competing Interest Statement H.W.C the senior and co-corresponding author of this study is the inventor of an issued EU patent and pending US patent owned by Icahn School of Medicine at Mount Sinai (Methods of Cardiac Repair, No. 12847330.3) regarding the use of CDX2 cells for heart repair. She is also the founder of a biotech VentriNova, Inc. that may benefit from the publication of the results presented regarding human CDX2 cells. Although the company is still in the early stages and seeking institutional financing, H.W.C. owns stock in the company.