Abstract 18887: Fetal-Derived Cdx2 Cells in Placenta Are Multipotent Cells With Cardiomyogenic Potential
Introduction: Stem cell based therapies for cardiac regeneration are of crucial importance and an ideal cell-type is yet to be established. Placenta is an easily available and rich source of multipotent cells. We previously demonstrated for the first time that fetal cells from placenta “home” to injured maternal myocardium to form cardiomyocytes and approximately 40% of the migrating cells expressed homeodomain protein Cdx2.
Hypothesis: Placental Cdx2 cells could be a novel source for cardiac repair.
Methods: Fetal-derived Cdx2 cells were labeled with eGFP using a cre-lox strategy wherein female virgin B6; 129S6-gt (ROSA) 26Sor<tm1 (CAG-tdTomato*,-EGFP*) Ees>/J43 mice were crossed with male B6.Cg-Tg (CDX2-cre) 101Erf/J mice. Isolated cells were assayed for in vitro cardiac differentiation and live cell imaging was carried out to capture spontaneous beating. Cdx2-eGFP cells were analyzed for clonal proliferation and their ability to differentiate into vascular lineages. The immunological profile of the purified Cdx2 cells was studied using flow cytometry and RNA array. Whole cell proteomic analysis of Cdx2-eGFP cells was carried out and compared with embryonic stem cells to infer the differences in protein expression patterns.
Results: Cdx2-eGFP cells differentiated into spontaneously beating cardiomyocytes and expressed structural proteins Cardiac troponin T(cTnT), α-sarcomeric actinin and gap junction protein Cx43. FISH analysis using mouse XY chromosome probes excluded fusion events. Further, Cdx2-eGFP cells underwent clonal expansion and differentiated into endothelial and smooth muscle lineages indicating their multipotent nature. Flow cytometry and RNA array demonstrated low expression of MHC molecules and components of the immune response, suggesting that these cells can evade host immune surveillance. Proteomic analysis revealed cell functions in Cdx2-eGFP cells that facilitate migration, homing and survival compared to the embryonic stem cells.
Conclusion: We have identified a novel multipotent cell-type in placenta exhibiting cardiomyogenic and vasculogenic potential. Our findings infer that Cdx2 cells may be very valuable in allogeneic cell therapy strategies for cardiac repair.
Author Disclosures: S. Vadakke-Madathil: None. A. Ranjan: None. J. Yoon: None. J. Tripodi: None. K. Raedschelders: None. S. Parker: None. V. Najfeld: None. J. Van EyK: None. H. Chaudhry: None.
- © 2016 by American Heart Association, Inc.