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

Bone marrow stem cells (BMSC) from adult mice are now believed to generate non-hematopoietic cell types. This newly defined property is referred to as stem cell plasticity. We tested the potential of lineage negative c-kit positive (Lin- c-kit+), GFP+ BMSC to differentiate into cardiac myocytes in myocardial infarcts produced by ligation of the left coronary artery. At 9 days post-transplant the hearts showed a band of developing GFP+ myocytes within the damaged myocardium. These GFP+ myocytes were positive for cardiac specific myosin and early expressed transcription factors. Endothelial cells and smooth muscle cells also developed from the donor bone marrow cells. Left ventricular end diastolic pressure (LVEDP) and left ventricular developed pressure (LVDP) were improved. Lin-c- kit- cells did not regenerate myocardium. We next tested the ability of cytokine-mobilized BMSC to regenerate myocardium. Nuclei in regenerating cardiomyocytes were positive for Csx/Nkx 2.5, GATA-4 and MEF2. Cytoplasmic proteins included desmin, nestin and connexin 43. Regenerating arterioles consisted of endothelial cells and smooth muscle cells positive for Ki67, and flkl. These regenerating vessels contained circulating TER119 positive red blood cells. Repair of infarcted myocardium resulted in improved heart function and survival. At day 27 after cytokine treatment and surgery, 11 of 15 mice survived compared with 9 of 52 non-treated mice. Left ventricular ejection fraction in infarcted hearts in cytokine-treated mice was 48%, 62% and 114% higher than the ejection fraction in non-treated mice at 9, 16 and 26 days following coronary artery occlusion. These findings demonstrate that circulating autologous stem cells traffic to the ischemic, infarcted myocardium and undergo differentiation into cardiomyocytes and vascular structures. We conclude that adult BMSC have the potential for repair in acute, ischemic heart disease.
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PMID:Stem cell repair in ischemic heart disease: an experimental model. 1243 Aug 44

It has been well documented that there are abundant endocrine progenitor cells in the neonatal pancreas. However, little is known of their relative proportions or even their phenotypes. The aim of this study was to examine the normal distribution and characteristics of putative endocrine precursor cells, identified by c-Kit or nestin expression, within the prenatal and postnatal rat pancreas during islet cell development. Here, we provide evidence of the existence of a subset of ductal, islet, and acinar cells with an immature morphology and high proliferative capacity that expressed c-Kit or nestin. The proportion of islet cells expressing c-Kit or nestin was highest at embryonic day 18 (25 +/- 4% and 28 +/- 6%) and decreased significantly by postnatal day 28 (P < 0.01), 1.3 +/- 0.2% and 5.7 +/- 1%, respectively. The expression of nestin mRNA decreased throughout development, while c-Kit mRNA expression was found to slightly increase in the developing pancreas. Coexpression patterns indicated that c-Kit and nestin form two distinct cell populations in the postnatal pancreas, and infrequently coexpress with other pancreatic cell-specific markers. Furthermore, decreased c-Kit and nestin expression in the islets in postnatal life correlated with an increase in cells immunopositive for Pdx-1 compared with birth (36 +/- 5% vs. 60 +/- 3%, P < 0.01), which accompanied a doubling in the proportion of Glut-2-positive cells (39.4 +/- 4% vs. 68.8 +/- 3%, P < 0.01), both of which are mature beta-cell markers. Taken together, these findings suggest that c-Kit- and nestin-expressing cells represent endocrine precursor cells that undergo marked changes in population dynamics during the transition from prenatal to postnatal pancreatic development in the rat. Characterization of the phenotype, relative abundance and location of these cells within the developing pancreas is an important step toward creating a strategy for isolating stem cell populations and modeling islet cell differentiation in vitro.
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PMID:Characterization of c-Kit and nestin expression during islet cell development in the prenatal and postnatal rat pancreas. 1504 5

Feeding a low-protein (LP) diet to pregnant and lactating rats impairs pancreatic islet mass and insulin release in the offspring, leading to glucose intolerance as adults. We hypothesized that an LP diet changes the number of pancreatic endocrine precursor cells or cells supporting endocrine cell neogenesis. Pregnant rats were given LP (8% protein) or a control (20% protein) diet from conception until postnatal d 21. Cells containing nestin, CD34, or c-Kit were quantified in pancreata of the offspring. Stellate cells immunoreactive for nestin were seen to be adjacent to ductal epithelium and were resident within the islets. These were proliferative and immunonegative for cytokeratin 20, fibronectin, tyrosine hydroxylase, pancreatic duodenal homeobox 1, Nk homeodomain transcription factor 6.1, or insulin, but expressed vimentin. Approximately 20% of islet nestin-positive cells also expressed the endothelial cell marker platelet endothelial cell adhesion molecule-1. Both ducts and islets also contained CD34- and c-Kit-positive cells with similar morphology to those expressing nestin. Offspring from rats fed the LP diet had significantly less nestin/CD34-positive cells and reduced expression of nestin mRNA. Within islets, there was an associated decrease in cell proliferation and in cells immunopositive for pancreatic duodenal homeobox 1. Nestin-positive cell number within islets correlated positively with the percent area of beta-cells. Supplementation of pregnant and lactating rats with taurine reversed the deficits in mean islet area and nestin-positive cells caused by the LP diet within the islets of the offspring. Nutritional programming of postnatal beta-cell mass may involve an altered abundance of cells expressing nestin and/or CD34, which may limit endocrine cell development.
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PMID:Low-protein diet during early life causes a reduction in the frequency of cells immunopositive for nestin and CD34 in both pancreatic ducts and islets in the rat. 1504 74

The ability of hematopoietic tissue-derived adult stem cells to transdifferentiate into neural progenitor cells offers an interesting alternative to central nervous system (CNS)- or embryonic-derived stem cells as a viable source for cellular therapies applied to brain regeneration. Umbilical cord blood (CB) due to its primitive nature and it unproblematic collection appears as a promising candidate for multipotent stem cell harvest. We developed a negative immunomagnetic selection method that depletes CB from hematopoietic lineage marker-expressing cells, hence isolating a discrete lineage negative (LinNeg) stem cell population (0.1% of CB mononucleated cell [MCN] population). In liquid culture supplemented with thrombopoietin, flt-3 ligand, and c-kit ligand (TPOFLK), CB LinNeg stem cells could expand primitive nonadherent hematopoietic progenitors (up to 47-fold) and simultaneously produce slow-dividing adherent cells with neuroglial progenitor cell morphology over 8 weeks. Laser scanning confocal microscopy analysis identified these adherent cells to express glial fibrillary acidic protein (GFAP). Gene expression analysis showed upregulation of primitive neuroglial progenitor cell markers including, GFAP, nestin, musashi-1, and necdin. ELISA quantification of liquid culture supernatant revealed the in vitro release of transforming growth factor beta-1 (TGFbeta1), glial cell line-derived neurotrophic factor (GDNF) suggesting their contribution to CB LinNeg stem cell transdifferentiation into neuroglial progenitors. Our study supports that a single CB specimen can be pre-expanded in TPOFLK to produce both primitive hematopoietic and neuropoietic progenitors, hence widening CB clinical potential for cellular therapies.
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PMID:Umbilical cord blood stem cells can expand hematopoietic and neuroglial progenitors in vitro. 1509 35

Ligation of the pancreatic duct has been shown to induce islet cell neogenesis from duct cells in the adult rat pancreas. The transcription factors that regulate islet cell neogenesis and the phenotype of putative precursor cells involved in neogenesis are unknown. We, therefore, studied the expression of the transcription factors Pdx1, Pbx1, Meis2, Nkx2.2 and the putative stem cell markers c-Kit and nestin in rat pancreata 3, 5 and 7 days after duct ligation. Immunocytochemical staining revealed a subpopulation of cells in the ligated portion of the pancreas that was positive for the putative stem cell markers c-Kit and nestin. The c-Kit immunoreactivity was upregulated, reaching a peak at day 3, while nestin expression peaked at day 7. The c-Kit-positive cells were located among the duct and islet cells, while nestin-expressing cells were found scattered in the duct epithelium at day 3 and around the ducts at day 7. Both c-Kit- and nestin-positive cells showed high proliferative activity, as determined by BrdU labeling. Pdx1 and Nkx2.2 were found predominantly in the duct cells of the ligated pancreas. There were significant changes in the expression patterns of Pbx1 and Meis2 in the ductular complexes. The findings indicate that the stem cell markers c-Kit and nestin as well as the transcription factors Pdx1 and Nkx2.2 are upregulated in compartments of the pancreas that are involved in islet cell neogenesis after duct ligation.
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PMID:Expression of stem cell markers and transcription factors during the remodeling of the rat pancreas after duct ligation. 1566 Feb 82

Ultrastructural and immunohistochemical studies of 4 groups of cells-(human embryonic stem cells (hES), embryoid bodies (EB), and spontaneously and retinoic acid (RA)-induced differentiating cells)-were carried out to investigate their detailed phenotype. Immunohistochemically, the EB cells showed strong immunoreactivity for CD34, CD117, and nestin. Differentiating cells expressed pancytokertin, vimentin, CD31, CD56, GFAP, nestin, and NeuN as well as CD34, and c-Kit. However, synaptophysin and neurofilaments were not present in these same differentiating cells. Transmission electron microscopy showed that hES and EB cells were very similar to germ cells or cells of the inner cell mass. Spontaneously and RA-induced differentiating cells exhibited epithelial, mesenchymal, endodermal, and neuronal phenotypes. The perikarya of the neuronal cells had rich RERs (Nissl substance) and long cytoplasmic processes filled with numerous neural tubules. However, neither synaptic junctions nor synaptic vesicles were developed. In our study, RA treatment with brain-derived growth factor and TGFalpha in neuron differentiation medium induced not only neuronal differentiation but also pluripotential differentiation. Full neuronal differentiation did not occur after 2 weeks in culture, as no synaptic junctions and synaptic vesicles developed.
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PMID:Ultrastructure of human embryonic stem cells and spontaneous and retinoic acid-induced differentiating cells. 1569 34

We describe here--presumably for the first time--a Cajal-like type of tubal interstitial cells (t-ICC), resembling the archetypal enteric ICC. t-ICC were demonstrated in situ and in vitro on fresh preparations (tissue cryosections and primary cell cultures) using methylene-blue, crystal-violet, Janus-Green B or MitoTracker-Green FM Probe vital stainings. Also, t-ICC were identified in fixed specimens by light microscopy (methylene-blue, Giemsa, trichrome stainings, Gomori silver-impregnation) or transmission electron microscopy (TEM). The positive diagnosis of t-ICC was strengthened by immunohistochemistry (IHC; CD117/c-kit+ and other 14 antigens) and immunofluorescence (IF; CD117/c-kit+ and other 7 antigens). The spatial density of t-ICC (ampullar-segment cryosections) was 100-150 cells/mm2. Non-conventional light microscopy (NCLM) of Epon semithin-sections revealed a network-like distribution of t-ICC in lamina propria and smooth muscle meshwork. t-ICC appeared located beneath of epithelium, in a 10-15 microm thick 'belt', where 18+/-2% of cells were t-ICC. In the whole lamina propria, t-ICC were about 9%, and in muscularis approximately 7%. In toto, t-ICC represent ~8% of subepithelial cells, as counted by NCLM. In vitro, t-ICC were 9.9+/-0.9% of total cell population. TEM showed that the diagnostic 'gold standard' (Huizinga et al., 1997) is fulfilled by 'our' t-ICC. However, we suggest a 'platinum standard', adding a new defining criterion- characteristic cytoplasmic processes (number: 1-5; length: tens of microm; thickness: < or =0.5 microm; aspect: moniliform; branching: dichotomous; organization: network, labyrinthic-system). Quantitatively, the ultrastructural architecture of t-ICC is: nucleus, 23.6+/-3.2% of cell volume, with heterochromatin 49.1+/-3.8%; mitochondria, 4.8+/-1.7%; rough and smooth endoplasmic-reticulum (1.1+/-0.6%, 1.0+/-0.2%, respectively); caveolae, 3.4+/-0.5%. We found more caveolae on the surface of cell processes versus cell body, as confirmed by IF for caveolins. Occasionally, the so-called 'Ca2+-release units' (subplasmalemmal close associations of caveolae+endoplasmic reticulum+mitochondria) were detected in the dilations of cell processes. Electrophysiological single unit recordings of t-ICC in primary cultures indicated sustained spontaneous electrical activity (amplitude of membrane potentials: 57.26+/-6.56 mV). Besides the CD117/c-kit marker, t-ICC expressed variously CD34, caveolins 1&2, alpha-SMA, S-100, vimentin, nestin, desmin, NK-1. t-ICC were negative for: CD68, CD1a, CD62P, NSE, GFAP, chromogranin-A, PGP9.5, but IHC showed the possible existence of (neuro)endocrine cells in tubal interstitium. We call them 'JF cells'. In conclusion, the identification of t-ICC might open the door for understanding some tubal functions, e.g. pace-making/peristaltism, secretion (auto-, juxta- and/or paracrine), regulation of neurotransmission (nitrergic/purinergic) and intercellular signaling, via the very long processes. Furthermore, t-ICC might even be uncommitted bipotential progenitor cells.
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PMID:Novel type of interstitial cell (Cajal-like) in human fallopian tube. 1596 70

Hepatocyte growth factor (HGF), a pleiotropic cytokine of mesenchymal origin promoting migration, proliferation, and survival in a wide spectrum of cells, can also modulate different biological responses in stem cells, but the mechanisms involved are not completely understood so far. In this context, we show that short-term exposure of mesenchymal stem cells (MSCs) to HGF can induce the activation of its cognate Met receptor and the downstream effectors ERK1/2, p38MAPK, and PI3K/Akt, while long-term exposure to HGF resulted in cytoskeletal rearrangement, cell migration, and marked inhibition of proliferation through the arrest in the G1-S checkpoint. When added to MSCs, the K252A tyrosine kinase inhibitor prevented HGF-induced responses. HGF's effect on MSC proliferation was reversed by p38 inhibitor SB203580, while the effects on cell migration were abrogated by PI3K inhibitor Wortmannin, suggesting that HGF acts through different pathways to determine its complex effects on MSCs. Prolonged treatment with HGF induced the expression of cardiac-specific markers (GATA-4, MEF2C, TEF1, desmin, alpha-MHC, beta-MHC, and nestin) with the concomitant loss of the stem cell markers nucleostemin, c-kit, and CD105.
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PMID:Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation. 1610 5

Transgenic rats expressing a mutated form of the human Cu/Zn superoxide dismutase (hSOD1(G93A)) develop an amyotrophic lateral sclerosis (ALS)-like phenotype, including motor neurone degeneration and reactive gliosis in the spinal cord. This study aimed at examining the presence of endogenous neural progenitors in the lumbar spinal cord of these rats at the end-stage of the disease. Immunohistochemical data clearly demonstrated the induced expression of the stem cell factor reported as a chemoattractant and survival factor for neural stem cells as well as nestin (neuro-epithelial stem cell intermediate filament) in the spinal cord sections. While the stem cell factor immunolabelling appeared diffuse throughout the gray matter, nestin labelling was restricted to clusters within the ventral horn. Interestingly, as paralysis regularly develops asymmetrically, induction of nestin was only detected on the ipsilateral side of the predominant symptoms. Finally, immunohistochemical detection of the stem cell factor receptor (c-Kit) revealed its specific induction which coincided with nestin immunolabelling. Together, these results are indicative of endogenous recruitment of neural progenitors within lesioned tissues and could support the development of treatments involving endogenous or exogenous stem cells.
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PMID:Unilateral induction of progenitors in the spinal cord of hSOD1(G93A) transgenic rats correlates with an asymmetrical hind limb paralysis. 1654 Feb 43

Previous studies of bone marrow-derived stem cell transdifferentiation into neurons have not involved purified cell populations and determined their exact phenotype prior to differentiation. The present study investigates whether highly purified mouse adult hematopoietic stem cells (HSCs), characterized by lineage marker depletion and expression of the cell surface markers Sca1 and c-Kit (Lin(-) Sca1(+) c-Kit(+) [LSK]), can be stimulated to adopt a neuronal fate. When the HSC(LSK) cells were cultured in vitro in neuronal differentiation medium supplemented with retinoic acid, 50% of the cells expressed the neural progenitor marker nestin and no cells had become postmitotic. Electrophysiological recordings on neuron-like cells showed that these cells were incapable of generating action potentials. When the HSC(LSK) cells either were grown in vitro together with neural precursor cells or were transplanted into the striatum or cerebellum of wild-type mouse, they either differentiated into Iba1-immunopositive macrophage/microglia or died. In conclusion, we demonstrate that adult HSC(LSK) cells do not have the capacity to leave the hematopoietic lineage and differentiate into neurons.
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PMID:Failure of transdifferentiation of adult hematopoietic stem cells into neurons. 1655 7


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