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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early-trimester human fetal pancreas is a promising potential source of pancreatic progenitor cells. However, the ethical controversy associated with the source of these cells, and technical difficulties associated with their differentiation into insulin-producing cells have limited both their availability and utility. This study aimed to characterize a population of pancreatic progenitor cells (PPCs) isolated from human fetus and describe the effects of a novel factor, PDZ-domain containing-2 (PDZD2), and its secreted form (sPDZD2), on PPC proliferation and differentiation. In particular, we examined and characterized the expression of several stem cell (nestin, ABCG2, c-kit), growth and differentiation markers (GLP-1R, c-met, erbB1), and PDZD2 in PPCs by RT-PCR, Western blot, and immunocytochemistry. We also examined the effects of sPDZD2 on PPC proliferation and differentiation by examining BrdU incorporation, MTT, cell number, and real-time PCR as well as ELISA. PPCs were isolated, cultured and characterized from human fetal pancreas. PDZD2 and sPDZD2 were detected at high levels in both human fetal pancreas and in PPCs. sPDZD2 acted as a potent mitogen on PPCs, and inhibited the differentiation of PPC-derived islet-like cell-clusters (ICCs), evidenced by the downregulation of Isl-1, Pdx-1, and insulin mRNA levels. sPDZD2 treatment also reduced levels of C-peptide in ICCs. These results show that a novel pancreatic developmental factor, PDZD2, is sufficient to promote the proliferation of human fetal PPCs while limiting differentiation of ICCs into islet/endocrine cells. Findings from this study will contribute to the development of improved methods for islet transplantation therapy in the treatment of diabetes.
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PMID:PDZ-domain containing-2 (PDZD2) is a novel factor that affects the growth and differentiation of human fetal pancreatic progenitor cells. 1803 33

Interstitial Cajal-like Cells (ICLC) were recently recognized in a plethora of non-digestive organs. Here, we describe a cell type of rat mesentery sharing ultrastructural and immunohistochemical features with ICLC. Mesenteric ICLC were demonstrated by transmission electron microscopy (TEM) and further tested by light microscope immunohistochemistry. The cell described here fulfils the TEM diagnostic criteria accepted for ICLC: location in the connective interstitium; close vicinity to nerves, capillaries and other interstitial cells; characteristic long, moniliform cell processes; specialized cell-to-cell junctions; caveolae; mitochondria at 5-10% of cytoplasmic volume; rough endoplasmic reticulum at about 1-2%; intermediate and thin filaments, microtubules; undetectable thick filaments. The processes of this mesenteric ICLC were particularly long, with a mean length of 24.91 microm (10.27-50.83 micorm), and a convolution index of 2.32 (1.37-3.63) was calculated in order to measure their potential length. Mean distances versus main target cells of ICLC-nerve bundles, vessels, adipocytes and macrophages-were 110.69, 115.80, 205.07 and 34.65 nm, respectively. We also tested the expression of CD117/c-kit, CD34, vimentin, alpha-smooth muscle actin, nestin, NK-1, tryptase and chymase and the antigenic profile of the mesenteric ICLC was comparable if not identical with that recently observed in ICLC from other extra-digestive tissues. Due to the peculiar aspect of the mesenteric ICLC processes it can be hypothesized that these cells form a three-dimensional network within the mesentery that is at the same time resistant and deformable following stretches consequent to intestine movements, mainly avoiding blood vessels closure or controlling blood vessels rheology. It remains, however, to be established if and how such cells are connected with the archetypal enteric ICC.
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PMID:Interstitial Cajal-like cells in rat mesentery: an ultrastructural and immunohistochemical approach. 1819 43

The objective of this study was to identify and characterize a self-renewing subpopulation of human ovarian tumor cells (ovarian cancer-initiating cells, OCICs) fully capable of serial propagation of their original tumor phenotype in animals. Ovarian serous adenocarcinomas were disaggregated and subjected to growth conditions selective for self-renewing, nonadherent spheroids previously shown to derive from tissue stem cells. To affirm the existence of OCICs, xenoengraftment of as few as 100 dissociated spheroid cells allowed full recapitulation of the original tumor (grade 2/grade 3 serous adenocarcinoma), whereas >10(5) unselected cells remained nontumorigenic. Stemness properties of OCICs (under stem cell-selective conditions) were further established by cell proliferation assays and reverse transcription-PCR, demonstrating enhanced chemoresistance to the ovarian cancer chemotherapeutics cisplatin or paclitaxel and up-regulation of stem cell markers (Bmi-1, stem cell factor, Notch-1, Nanog, nestin, ABCG2, and Oct-4) compared with parental tumor cells or OCICs under differentiating conditions. To identify an OCIC cell surface phenotype, spheroid immunostaining showed significant up-regulation of the hyaluronate receptor CD44 and stem cell factor receptor CD117 (c-kit), a tyrosine kinase oncoprotein. Similar to sphere-forming OCICs, injection of only 100 CD44(+)CD117(+) cells could also serially propagate their original tumors, whereas 10(5) CD44(-)CD117(-) cells remained nontumorigenic. Based on these findings, we assert that epithelial ovarian cancers derive from a subpopulation of CD44(+)CD117(+) cells, thus representing a possible therapeutic target for this devastating disease.
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PMID:Identification and characterization of ovarian cancer-initiating cells from primary human tumors. 1851 91

Stem cells are self-renewing multipotent progenitors with the broadest developmental potential in a given tissue at a given time. Normal stem cells in the adult organism are responsible for renewal and repair of aged or damaged tissue. Adult stem cells are present in virtually all tissues and during most stages of development. In this review, we introduce the reader to the basic information about the field. We describe selected stem cell isolation techniques and stem cell markers for various stem cell populations. These include makers for endothelial progenitor cells (CD146/MCAM/MUC18/S-endo-1, CD34, CD133/prominin, Tie-2, Flk1/KD/VEGFR2), hematopoietic stem cells (CD34, CD117/c-Kit, Sca1), mesenchymal stem cells (CD146/MCAM/MUC18/S-endo-1, STRO-1, Thy-1), neural stem cells (CD133/prominin, nestin, NCAM), mammary stem cells (CD24, CD29, Sca1), and intestinal stem cells (NCAM, CD34, Thy-1, CD117/c-Kit, Flt-3). Separate section provides a concise summary of recent clinical trials involving stem cells directed towards improvement of a damaged myocardium. In the last part of the review, we reflect on the field and on future developments.
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PMID:Adult stem cells and their trans-differentiation potential--perspectives and therapeutic applications. 1862 66

Pancreatic stem cells (PSC) have proved their high plasticity by differentiating into cell types of all three germ layers after the formation of organoid bodies. Motivated by this high differentiation potential this study focused on the immanent stem cell, endothelial and epithelial characteristics of PSC to elucidate whether PSC are a possible source for a stem cell-based in vitro model for screening of pharmaceutical substances. Furthermore, it was investigated whether marker expression was influenced by application of protocols for inducing endothelial or epithelial differentiation originating from research with mesenchymal stem cells or by cultivation on extracellular matrices (ECM). PSC showed expression of relevant stem cell markers CD 45, nestin, Oct 4 and c-kit. As endothelial characteristics they displayed the markers endoglin, VCAM 1, VEGFR 1 and vWF as well as the formation of vessel-like structures. Those endothelial properties were not further intensified by application of protocols employing vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF) and endothelial cell growth medium. As typical epithelial characteristics PSC showed expression of keratin 7, 8, 18 and 19, ZO-1 and catenin beta1. In order to induce epithelial differentiation PSC were cocultured with the lung epithelial cell lines A549 and Calu-3 either by the usage of conditioned medium or by cultivation of PSC on fixed epithelial cells. Depending on the applied coculture system and epithelial cell type used expression of the epithelial marker cadherin-1 was altered compared to control. Cultivation on different ECM changed expression of all investigated markers only marginally. These results confirm that PSC possess endothelial and epithelial properties. Furthermore, epithelial characteristics represented by expression of CDH 1 were altered by coculture with epithelial cell lines.
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PMID:Differentiation potential of human pancreatic stem cells for epithelial- and endothelial-like cell types. 1869 69

Directed differentiation of embryonic stem cells indicates that mesodermal lineages in the mammalian heart (cardiac, endothelial, and smooth muscle cells) develop from a common, multipotent cardiovascular precursor. To isolate and characterize the lineage potential of a resident pool of cardiovascular progenitor cells (CPcs), we developed BAC transgenic mice in which enhanced green fluorescent protein (EGFP) is placed under control of the c-kit locus (c-kit(BAC)-EGFP mice). Discrete c-kit-EGFP(+) cells were observed at different stages of differentiation in embryonic hearts, increasing in number to a maximum at about postnatal day (PN) 2; thereafter, EGFP(+) cells declined and were rarely observed in the adult heart. EGFP(+) cells purified from PN 0-5 hearts were nestin(+) and expanded in culture; 67% of cells were fluorescent after 9 days. Purified cells differentiated into endothelial, cardiac, and smooth muscle cells, and differentiation could be directed by specific growth factors. CPc-derived cardiac myocytes displayed rhythmic beating and action potentials characteristic of multiple cardiac cell types, similar to ES cell-derived cardiomyocytes. Single-cell dilution studies confirmed the potential of individual CPcs to form all 3 cardiovascular lineages. In adult hearts, cryoablation resulted in c-kit-EGFP(+) expression, peaking 7 days postcryolesion. Expression occurred in endothelial and smooth muscle cells in the revascularizing infarct, and in terminally differentiated cardiomyocytes in the border zone surrounding the infarct. Thus, c-kit expression marks CPc in the neonatal heart that are capable of directed differentiation in vitro; however, c-kit expression in cardiomyocytes in the adult heart after injury does not identify cardiac myogenesis.
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PMID:c-kit expression identifies cardiovascular precursors in the neonatal heart. 1957 Sep 94

Heart disease is the leading cause of death in the industrialized world, and stem cell therapy seems to be a promising treatment for injured cardiac tissue. To reach this goal, the scientific community needs to find a good source of stem cells that can be used to obtain new myocardium in a very period range of time. Since there are many ethical and technical problems with using embryonic stem cells as a source of cells with cardiogenic potential, many laboratories have attempted to isolate potential cardiac stem cells from several tissues. The best candidates seem to be cardiac "progenitor" and/or "stem" cells, which can be isolated from subendocardial biopsies from the same patient or from embryonic and/or fetal myocardium. Regardless of the technique used to isolate and characterize these cells, it appears that the different cells isolated from adult myocardium to date are all phenotypic variations of a unique cell type that expresses several markers, such as c-Kit, CD34, MDR-1, Sca-1, CD45, nestin, or Isl-1, in various combinations.
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PMID:Cardiac stem cell research: an elephant in the room? 1924 73

Parathyroid tissue is able to spontaneously induce angiogenesis, proliferate, and secrete parathyroid hormone when autotransplanted in patients undergoing total parathyroidectomy. Angiogenesis is also involved in parathyroid tumorigenesis. Here we investigated the anatomical and molecular relationship between endothelial and parathyroid cells within human parathyroid glands. Immunohistochemistry for CD34 antigen identified two subpopulations in normal and tumoral parathyroid glands: one constituted by cells lining small vessels that displayed endothelial antigens (factor VIII, isolectin, laminin, CD146) and the other constituted of single cells scattered throughout the parenchyma that did not express endothelial markers. These parathyroid-derived CD34(+) cells were negative for the hematopoietic and mesenchymal markers CD45, Thy-1/CD90, CD105, and CD117/c-kit; however, a subset of CD34(+) cells co-expressed the parathyroid specific genes glial cell missing B, parathyroid hormone, and calcium sensing receptor. When cultured, these cells released significant amount of parathyroid hormone. Parathyroid-derived CD34(+) cells, but not CD34(-) cells, proliferated slowly and differentiated into mature endothelial cells. CD34(+) cells from parathyroid tumors differed from those derived from normal parathyroid glands as: 1) they were more abundant and mainly scattered throughout the parenchyma; 2) they rarely co-expressed CD146; and 3) a fraction co-expressed nestin. In conclusion, we identified cells expressing endothelial and parathyroid markers in human adult parathyroid glands. These parathyroid/endothelial cells were more abundant and less committed in parathyroid tumors compared with normal glands, showing features of endothelial progenitors, which suggests that they might be involved in parathyroid tumorigenesis.
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PMID:Expression of parathyroid-specific genes in vascular endothelial progenitors of normal and tumoral parathyroid glands. 1964 13

Pluripotent mesenchymal stem-like cell lines were established from lungs of 3-4 months old aborted fetus. The cells present the high ex vivo expansion potential of MSC, a typical fibroblast-like morphology and proliferate up to 15 passages without displaying clear changes in morphology. Immunological localization and flow cytometry analyses showed that these cells are positive for OCT4, c-Kit, CD11, CD29, CD44, telomerase, CD106, CD105, CD166, and SSEA1, weakly expression or negative for SSEA1, SSEA3, SSEA4, CD34, CD105 and CD106. These cells can give rise to the adipogenic as evidenced by accumulation of lipid-rich vacuoles within cells identified by Oil-red O when they were induced with 0.5 mM isobutylmethylxanthine, 200 microM indomethacin, 10(-6)M dexamethasone, and 10 microg/ml of insulin in high-glucose DMEM. Osteogenic lineage cells were generated in 0.1 microM dexamethasone, 50 microg/ml ascorbic acid, 10 mM beta-glycerophosphate, which are shaped as the osteoblastic morphology, expression of alkaline phosphatase (AP), and the formation of a mineralized extracellular matrix identified by Alizarin Red staining. Neural cells are observed when the cultures were induced with 2-mercapometal, which are positive for nestin, NF-100, MBP and GFAP. Additionally, embryoid bodies (EBs) and sperm like cells are obtained in vitro differentiation of these lung MSCs induced with 10(-5)M retinoic acid (RA). These results demonstrated that these MSCs are pluripotent and may provide an in vitro model to study germ-cell formation and also as a potential source of sperms for male infertility.
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PMID:Characterization of mesenchymal stem cells (MSCs) from human fetal lung: potential differentiation of germ cells. 1965 22

Novel human embryonal stem cell lines C612 and C910 have been established from hatching blastocytes. Cells were cultivated in mTeST medium on mouse fibroblast feeder-layers. They express common pluripotent markers such as alkaline phosphatase, Oct 3/4, SEEA-4, Nanog, Rex1. Immunophenotyping of these cells by flow cytometry revealed expression of CD90 (Thy-1) and CD117 (c-kit) antigens and weak or no expression of CD13, CD34, CD45, CD130, HLA class I and HLA class II antigens. This pattern of surface antigen expression is common for human embryonic stem cells. G-banding assay of C612 and C910 metaphase plates showed that karyotypic structure of these cells was normal both in chromosome number and structure. The cells are pluripotent because of their capability to generate embryoid bodies, undergo spontaneous differentiation and express markers of all germ layers: nestin, keratin, vimentin (ectoderm), alpha-fetoprotein (entoderm), and muscle alpha-actinin (mesoderm). Thus, C612 and C910 cells have all attributes of typical human embryonic stem cells (diploid, capable of self-renewal, express pluripotent markers and differentiate into three germ layers) and may be of potential use for fundamental and regenerative medicine researches.
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PMID:[Novel human embryonic stem cell lines C612 and C910]. 1976 46


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