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 multipotentiality. 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.
Background: In this study we surveyed over 200 healthcare leaders who hold high level management positions across institutions regarding their use and awareness of social media. Method: An online and on-site survey was used to gather information about social media use. Results: The survey found that that healthcare leaders have very little awareness of social media use in their organizations. The survey also found that they mostly use social media for personal purposes and that use is limited to two platforms, Facebook and LinkedIn. In addition, it became clear that patient engagement and research or professional collaborations through social media are not within their scope of activities. Conclusions: More education and awareness is needed in this area. Since social media is gaining presence in all areas of healthcare it is important to raise awareness to its proper use and potential.
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.
The limited regeneration of adult mammalian heart has prompted the need to recognize novel strategies that can restore contractile function in heart disease. However, in cell-based therapies the lack of an appropriate cell-type that can differentiate to cardiomyocytes in vivo persists as an ultimate unmet need. Our prior study demonstrates that experimental myocardial injury in pregnant mice triggers the flux of fetal cells via the maternal circulation into the injured heart where they undergo differentiation into diverse cardiac cell fates. Among those fetal cells, the expression of Caudal type homeobox2 (Cdx2); a trophoblast stem cell marker was unique. To understand the intriguing role of placental Cdx2 cells in cardiomyogenesis, we utilized a lineage-tracing strategy to label fetal-derived Cdx2 cells with enhanced green fluorescent protein (Cdx2-eGFP). Cdx2-eGFP cells were characterized and assayed for cardiac differentiation in vitro and in vivo using a mouse model of myocardial infarction. Cdx2-eGFP cells clonally proliferated and differentiated into spontaneously beating cardiomyocytes and vascular cells in vitro , signifying a multipotent nature compared to the Cdx2 negative cell population. When administered via tail vein to infarcted wild-type male mice, Cdx2-eGFP cells selectively and robustly homed to the injured heart and differentiated to cardiomyocytes and blood vessels, significantly improving the contractility noted by magnetic resonance imaging. Proteomics and immune transcriptomics studies of Cdx2-eGFP cells compared to embryonic stem (ES) cells reveal that they appear to retain ‘stem’-related functions of ES cells, but exhibit unique signatures for homing and survival in addition to being immunologically naive. Blocking CXCR4, during the migration of Cdx2-eGFP cells to SDF1α suggested a possible role for SDF1-CXCR4 signaling in the mechanistic basis of homing. Advancing towards a translational role, we demonstrate that CDX2 expressing cells can be isolated from the chorionic region of human term placenta. Our results herein may represent a paradigmatic shift in the way we approach early embryonic lineages and cell fate choices and will establish the translational potential of placental Cdx2 cells for cardiac repair.
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