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Clinical evidence suggests that the prevalence of cardiac disease is lower in premenopausal women compared to postmenopausal women and men. Although multiple factors contribute to this difference, uterine stem cells may be a major factor, as a high abundance of these cells are present in the uterus. Uterine-derived stem cells have been reported in several studies as being able to contribute to cardiac neovascularization after injury. However, our studies uniquely show the presence of an "utero-cardiac axis", in which uterine stem cells are able to home to cardiac tissue to promote tissue repair. Additionally, we raise the possibility of a triangular relationship among the bone marrow, uterus, and heart. In this review, we discuss the exchange of stem cells across different organs, focusing on the relationship that exists between the heart, uterus, and bone marrow. We present increasing evidence for the existence of an utero-cardiac axis, in which the uterus serves as a reservoir for cardiac reparative stem cells, similar to the bone marrow. These cells, in turn, are able to migrate to the heart in response to injury to promote healing. [ABSTRACT FROM AUTHOR]

Canopy FGF signaling regulator 2 (CNPY2) is a FGF21-modulated protein containing a saposin B-type domain. In vitro studies have shown CNPY2 is able to enhance neurite outgrowth in neurons and stabilize the expression of low density lipoprotein receptor in macrophages and hepatocytes. However, no in vivo data are available on the normal expression of CNPY2 and information is lacking on which cell types express this protein in tissues. To address this, the present study examined CNPY2 expression at the mRNA and protein levels. Quantitative PCR and ELISA examination of mouse tissues showed that CNPY2 varies between organs, with the highest expression in the heart, lung and liver. Immunohistochemistry detected CNPY2 in a variety of cell types including skeletal, cardiac and smooth muscle myocytes, endothelial cells and epithelial cells. CNPY2 was also detectable in mouse blood and human and mouse uteri. These data demonstrate CNPY2 is widely distributed in tissues and suggest the protein has biological functions that have yet to be identified. Using these new observations we discuss possible functions of the protein. [ABSTRACT FROM AUTHOR]

Cell therapy to prevent cardiac dysfunction after myocardial infarction (MI) is less effective in aged patients because aged cells have decreased regenerative capacity. Allogeneic transplanted stem cells (SCs) from young donors are usually rejected. Maintaining transplanted SC immunoprivilege may dramatically improve regenerative outcomes. The uterus has distinct immune characteristics, and we showed that reparative uterine SCs home to the myocardium post-MI. Here, we identify immunoprivileged uterine SCs and assess their effects on cardiac regeneration after allogeneic transplantation. We found more than 20% of cells in the mouse uterus have undetectable MHC I expression by flow cytometry. Uterine MHC I (neg) and MHC I (pos) cells were separated by magnetic cell sorting. The MHC I (neg) population expressed the SC markers CD34, Sca-1 and CD90, but did not express MHC II or c-kit. In vitro , MHC I (neg) and (pos) SCs show colony formation and endothelial differentiation capacity. In mixed leukocyte co-culture, MHC I (neg) cells showed reduced cell death and leukocyte proliferation compared to MHC I (pos) cells. MHC I (neg) and (pos) cells had significantly greater angiogenic capacity than mesenchymal stem cells. The benefits of intramyocardial injection of allogeneic MHC I (neg) cells after MI were comparable to syngeneic bone marrow cell transplantation, with engraftment in cardiac tissue and limited recruitment of CD4 and CD8 cells up to 21 days post-MI. MHC I (neg) cells preserved cardiac function, decreased infarct size and improved regeneration post–MI. This new source of immunoprivileged cells can induce neovascularization and could be used as allogeneic cell therapy for regenerative medicine. [ABSTRACT FROM AUTHOR]