Discovery of a multipotent cell type from the term human placenta

Abstract

The human placenta is a reservoir of a multitude of cell types with immense regenerative potential. Caudal-type homeobox-2 (CDX2) is a conserved factor that regulates trophectoderm formation and placentation during early embryonic development and hence can play a vital role in understanding developmentally conserved regenerative mechanisms. Cdx2 lineage tracing in our previous study identified multipotent Cdx2 lineage cells in the mouse placenta 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 chorionic placenta and are uniquely committed to cardiovascular differentiation. We examined the term placentas from 106 healthy donors 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. Bringing us a step closer to translation, our study identifies an easily accessible and ethically feasible cell source to facilitate therapeutic strategies for cardiovascular disease.