Multipotent fetal-derived Cdx2 cells from placenta regenerate the heart

Sangeetha Vadakke-Madathil, Gina LaRocca, Koen Raedschelders, Jesse Yoon, Sarah J. Parker, Joseph Tripodi, Vesna Najfeld, Jennifer E. Van Eyk, Hina W. Chaudhry

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The extremely limited regenerative potential of adult mammalian hearts has prompted the need for novel cell-based therapies that can restore contractile function in heart disease. We have previously shown the regenerative potential of mixed fetal cells that were naturally found migrating to the injured maternal heart. Exploiting this intrinsic mechanism led to the current hypothesis that Caudal-type homeobox-2 (Cdx2) cells in placenta may represent a novel cell type for cardiac regeneration. Using a lineage-tracing strategy, we specifically labeled fetal-derived Cdx2 cells with enhanced green fluorescent protein (eGFP). Cdx2-eGFP cells from end-gestation placenta were assayed for cardiac differentiation in vitro and in vivo using a mouse model of myocardial infarction. We observed that these cells differentiated into spontaneously beating cardiomyocytes (CMs) and vascular cells in vitro, indicating multi-potentiality. When administered via tail vein to infarcted wild-type male mice, they selectively and robustly homed to the heart and differentiated to CMs and blood vessels, resulting in significant improvement in contractility as noted by MRI. Proteomics and immune transcriptomics studies of Cdx2-eGFP cells compared with embryonic stem (ES) cells reveal that they appear to retain “stem”-related functions of ES cells but exhibit unique signatures supporting roles in homing and survival, with an ability to evade immune surveillance, which is critical for cell-based therapy. Cdx2-eGFP cells may potentially represent a therapeutic advance in allogeneic cell therapy for cardiac repair.

Original languageEnglish
Pages (from-to)11786-11795
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number24
DOIs
StatePublished - 11 Jun 2019

Keywords

  • Cardiac regeneration
  • Cardiomyocytes
  • Cdx2
  • Placenta
  • Stem cells

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