Abstract 198: Multipotent Placenta-derived Cdx2 Cells Possess in vitro and in vivo Cardiomyogenic Potential

Abstract

Stem cell-based therapies for cardiac regeneration are of crucial importance and an ideal cell-type is yet to be established. We previously reported that fetal cells from placenta “home” to injured maternal heart and approximately 40% (40/100) of the migrating cells expressed homeodomain protein Cdx2. This interesting observation led us to hypothesize that placental Cdx2 could be a novel cell target for cardiac differentiation. To understand this phenomenon, we employed a cre-lox strategy that labeled Cdx2 cells in placenta with e-GFP and induced myocardial infarction (MI) in pregnant mice at mid-gestation. The maternal heart was analyzed 4 weeks post-MI for the presence of Cdx2-eGFP-derived cardiomyocytes. Additionally, Cdx2 cells were isolated from late-gestation placenta and assayed for cardiac differentiation in vitro followed by live cell imaging. Phenotypic and whole-cell proteomic analysis, clonal and vascular lineage differentiation and immune profiling were carried out subsequently. We observed that Cdx2 cells migrated to injured maternal hearts and differentiated into cardiomyocytes highlighting the functional significance of fetal-maternal stem cell transfer. Additionally, isolated Cdx2 cells from the late placenta differentiated into spontaneously beating cardiomyocytes and expressed structural proteins cardiac troponin T(cTnT), α-sarcomeric actinin and gap junction protein Cx43. These cells underwent clonal expansion and differentiated into endothelial and smooth muscle lineages in culture indicative of their multipotent nature. Low expression of MHC molecules and other components of the immune-response, infer that these cells possess the ability to evade host immune surveillance. Proteomic analysis demonstrated that 145 proteins were uniquely identified in the Cdx2 cells compared to embryonic stem cells. These protein networks reflected an increased activation of functions involving migration, fertility, homing, and chemotaxis. Our study is the first to demonstrate that Cdx2 may play a role in cardiac differentiation and delineate multipotent cells in placenta with an inherent “homing” ability. These findings point to a potential role for Cdx2 cells in cardiac regenerative therapies using allogeneic cells.