Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have documented the presence of stem cells within the myocardium and their role in the repair of ischaemic injury. Nevertheless, the pathogenic role of stem cells in non-ischaemic myocardial diseases, as well as the factors potentially responsible for their activation, is still under debate. The present study demonstrates the presence of an increased number of c-kit positive, MDR-positive, and Sca-1-positive stem cells within the myocardium of hereditary delta-SG null hamsters, a spontaneously occurring model of hypertrophic cardiomyopathy. When hamsters are 80 days old, ie at the 'hypertrophic' stage of the disease, but without haemodynamic overload, these cells associate with a multitude of cells co-expressing c-kit, cMet, GATA4, or MEF-2, and proliferating myocytes co-expressing myosin heavy chain, telomerase, ki67 and cyclin B. Furthermore, at the same animal age, the number of myocardial cells co-expressing c-kit and Flk-1, and the number of capillary vessels, is also amplified. In order to identify factors potentially responsible for stem cell activation, the myocardial expression of HGF and cMet and HGF plasma levels were evaluated, demonstrating their increase in 80-day-old delta-SG null hamsters. To demonstrate the possible ability of HGF to induce stem cell differentiation, bone-marrow-derived mesenchymal stem cells were challenged with HGF at the same plasma concentration observed in vivo. HGF induced cMet phosphorylation, and caused loss of stem cell features and overexpression of MEF-2, TEF1, and MHC. Our results demonstrate that stem cell activation occurs within the cardiomyopathic myocardium, very likely to maintain an efficient cardiac architecture. In this context, elevated levels of HGF might play a role in induction of stem cell commitment to the cardiomyocyte lineage and in cardioprotection through its anti-apoptotic action. Consistently, when cytokine levels declined to physiological concentrations, as in 150-day-old cardiomyopathic animals, myocardial apoptosis prevailed, prejudicing cardiac function.
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PMID:Stem cell activation sustains hereditary hypertrophy in hamster cardiomyopathy. 1568 36

Here we have analyzed the behavior and fate of stem cells from human umbilical cord blood (scHUCBs) when grafted into the myocardial wall of normal and damaged hearts of chicken embryos. We started by characterizing the scHUCBs before grafting and we found that they express precardiogenic genes including Nkx2.5, GATA4, MEF-2, and SERCA2a together with undifferentiation markers as CD34 or c-kit. In grafting experiments using scHUCBs labeled with DiI we observed that these cells were not rejected by the host and survived when implanted in chicken hearts, being able to migrate through the myocardial wall. By 3 days after grafting we found labeled cells with morphological characters of myocardiocytes in concordance with the identification of the expression of human genes for myosin light chain 2a (Mlc2a) and myosin heavy chain-beta (Mhc beta) in the chicken heart. When a small injury was applied to the heart wall, grafted scHUCBs were vigorously attracted by the damaged myocardium. This directed migration was only sustained for 12 h after injury, time period required for healing of the damaged heart wall. The rate of myocardial differentiation of scHUCBs in damaged hearts was not significantly increased with respect to that found when implanted in healthy hearts. However, we found stimulation of endothelial differentiation in injured hearts deduced by the increased expression of human genes for platelet endothelial cell-adhesion molecule 1 or vascular endothelial growth factor receptor 2 and the presence of DiI-labeled endothelial cells. Together all these findings support the embryonic chicken heart as a feasible model for experimentation in stem cell therapy and emphasize the relevance of the physiological conditions of the myocardial host tissue for engraftment and differentiation of exogenously applied scHUCBs.
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PMID:Migration and differentiation of human umbilical cord stem cells after heart injury in chicken embryos. 1839 37

Stem cell capability enhanced with cytokine administration is a promising treatment for myocardial infarction. Bone marrow stem cells (BMSCs) were isolated from C57BL/6 mice (8-12 weeks old) expressing GFP and characterized with c-kit and CD34. Infarcted heart tissue fragments were placed into dishes with BMSCs and medium supplemented with G-CSF, SCF, IGF-1 or combinations thereof were given to the BMSC-infarcted myocardium in vitro model. The IGF-1-G-CSF group showed significantly higher migration (67.7% +/- 2.6) of c-kit(+) BMSCs towards the ischemic tissue and expressed MEF-2 (43.7% +/- 1.7). Of the single treatment groups, the G-CSF group demonstrated significantly higher migration of c-kit(+) BMSCs (60.5 +/- 2.7) with MEF-2 expression (38.7 +/- 1.4). IGF-1 complements G-CSF and was relatively more significant in its effects on BMSC migration and cardiac lineage commitment towards ischemic heart tissue.
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PMID:IGF-1 and G-CSF complement each other in BMSC migration towards infarcted myocardium in a novel in vitro model. 1928 66