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)

Epimorphin, a mesenchymal cell surface-associated molecule, is detected on hepatic stellate cells (HSCs) in the liver. Here, we show the involvement of epimorphin in differentiation of rat hepatic stem-like cells (HSLCs) through contact with HSCs. HSLCs, isolated from adult rats, cultured in stellate cell-conditioned medium had no phenotypic and morphological changes, whereas HSLCs co-cultured with HSCs expressed albumin, transferrin, and tyrosine aminotransferase. An anti-epimorphin antibody inhibited hepatocytic differentiation of HSLCs in co-culture. Furthermore, epimorphin induced mRNA expression of albumin, transferrin, tyrosine aminotransferase, and gamma-glutamyl transpeptidase with decrease of c-kit and musashi-1. Morphologically, HSLCs piled up when co-cultured with HSCs, which was dramatically inhibited by an anti-epimorphin antibody. HSLCs contact with epimorphin started piling up, changed their shape from flat to cuboidal, and subsequently developed bile-canaliculi-like structures. In conclusion, epimorphin is a factor that induces differentiation of hepatic stem-like cells through epithelial-mesenchymal cell contact.
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PMID:Epimorphin is involved in differentiation of rat hepatic stem-like cells through cell-cell contact. 1459 30

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

Focal injury of the adult liver causes formation of granulomatous tissue and fibrosis. When thermoreversible gelation polymer (TGP) was applied to such defects of the rat liver, complete recovery of hepatic tissues was observed without granulation. We analyzed the mechanism of the regeneration. TGP is a chemically synthesized biocompatible polymer material whose sol-gel transition is reversible by changing the temperature. Cooled TGP was poured into a penetration lesion of the rat liver. Immunohistochemistry and polymerase chain reaction were carried out using tissues and cultured cells isolated from ductular structures. Immunocytochemical and ultrastructural analyses were also conducted. Seven days after TGP treatment, ductular reactions were observed around the wound and ductules elongated to the injured area. Cells in the structures were alpha-fetoprotein (AFP) positive, albumin+, CK19+, c-Kit+, and Thyl+. Hepatocyte-like cells possessing glycogen appeared around the tips of the ductules from day 9. The defect was completely replaced with hepatocytes by day 28. Cells isolated from the ductules expressed Musashi-1, c-Kit, Thyl, AFP, albumin, transferrin, connexin 43, and CK19. When the cultured cells were covered by TGP, they rapidly proliferated to form colonies, whereas without TGP cells gradually died. Morphologically and ultrastructurally the cells were similar to hepatocytes. They expressed not only albumin and transferrin but TAT, CYP2E1, and CCAAT/enhancer binding protein a. Some cells formed bile canaliculus-like structures. In conclusion, TGP may trigger the initiation of hepatic stem cells in biliary ductules, and stem cell activation may occur even in the regeneration of the normal liver.
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PMID:Thermoreversible gelation polymer induces the emergence of hepatic stem cells in the partially injured rat liver. 1662 35

We report the presence of neural crest-derived corneal precursors (COPs) that initiate spheres by clonal expansion from a single cell. COPs expressed the stem cell markers nestin, Notch1, Musashi-1, and ABCG2 and showed the side population cell phenotype. COPs were multipotent with the ability to differentiate into adipocytes, chondrocytes, as well as neural cells, as shown by the expression of beta-III-tubulin, glial fibrillary acidic protein, and neurofilament-M. COP spheres prepared from E/nestin-enhanced green fluorescent protein (EGFP) mice showed induction of EGFP expression that was not originally observed in the cornea, indicating activation of the neural-specific nestin second intronic enhancer in culture. COPs were Sca-1(+), CD34(+), CD45(-), and c-kit(-). Numerous GFP(+) cells were observed in the corneas of mice transplanted with whole bone marrow of transgenic mice ubiquitously expressing GFP; however, no GFP(+) COP spheres were initiated from these mice. On the other hand, COP spheres from transgenic mice encoding P0-Cre/Floxed-EGFP as well as Wnt1-Cre/Floxed-EGFP were GFP(+), indicating the neural crest origin of COPs, which was confirmed by the expression of the embryonic neural crest markers Twist, Snail, Slug, and Sox9. Taken together, these data indicate the existence of neural crest-derived, multipotent stem cells in the adult cornea.
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PMID:Isolation of multipotent neural crest-derived stem cells from the adult mouse cornea. 1688 82

Head and neck cancer is the fifth most common malignancy and accounts for 3% of all new cancer cases each year. Despite relatively high survival rates, the quality of life of these patients is severely compromised because of radiation-induced impairment of salivary gland function and consequential xerostomia (dry mouth syndrome). In this study, a clinically applicable method for the restoration of radiation-impaired salivary gland function using salivary gland stem cell transplantation was developed. Salivary gland cells were isolated from murine submandibular glands and cultured in vitro as salispheres, which contained cells expressing the stem cell markers Sca-1, c-Kit and Musashi-1. In vitro, the cells differentiated into salivary gland duct cells and mucin and amylase producing acinar cells. Stem cell enrichment was performed by flow cytrometric selection using c-Kit as a marker. In vitro, the cells differentiated into amylase producing acinar cells. In vivo, intra-glandular transplantation of a small number of c-Kit(+) cells resulted in long-term restoration of salivary gland morphology and function. Moreover, donor-derived stem cells could be isolated from primary recipients, cultured as secondary spheres and after re-transplantation ameliorate radiation damage. Our approach is the first proof for the potential use of stem cell transplantation to functionally rescue salivary gland deficiency.
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PMID:Rescue of salivary gland function after stem cell transplantation in irradiated glands. 1844 41

Bone marrow derived mesenchymal stem cells (BM-MSCs) take part in the colonic mucosal regeneration. They are multipotent cells, which can be identified with both negative (i.e. CD13, CD 14, CD45, c-Kit, major histocompatibility complex /MHC class I and II) and positive (i.e. CD54 (ICAM1), CD133, CD146 (MCAM), CD166, Flk-1, Sca-1, Thy-1, stage-specific antigen I /SSEA-I and Musashi-1, HLA class I) markers. These cells can repopulate the gastrointestinal mucosa as they may differentiate into stromal- (i.e. myofi-broblast) or epithelial-like (Paneth-, epithel-, goblet or enteroendocrin) cells without proliferation. During the mesenchymal to epithelial transition (MET) stem cells enter the epithelial layer and take up epithelial cell-like properties. Rarely BM-MSCs may retain their stem cell characteristics and are capable of producing progeny. The isolated lymphoid aggregates may serve as a platform from where BM-MSCs migrate to the nearby crypts as mediated by several chemoattractant proteins, which are expressed in injured tissue. The number of BM-MSCs is influenced by the degree of inflammation. In this review we summarize the current information about the role of BM-MSCs in the repair progress of injured colonic epithelium and their potential clinical applications.
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PMID:The role of the bone marrow derived mesenchymal stem cells in colonic epithelial regeneration. 2040 50

It is thought that the regenerative capacity of the mammary gland following post-lactation involution resides in multipotent stem cells within the luminal tissue. Adult stem cells make up a small percentage of the cells found in mature organ systems, however to define useful markers has long been a challenge. c-Kit (KIT) and its ligand stem cell factor (KITLG), ATP-binding cassette sub-family G member 2 (ABCG2) and Musashi 1 (MSI1) are good candidate to identify progenitor cells in their niche. Using real-time PCR we showed that KIT, KITLG and MSI1 expressions were up regulated before lambing and at involution relatively to prepubertal stage. The in situ hybridization analysis for KIT gene confirmed and localized the expression in luminal epithelial cells. The changes in the expression profile of putative stem cell markers in mammary glands of sheep suggest that they modify with the progression of lactation cycle, being up regulated during differentiation and down regulated during lactation.
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PMID:Expression of putative stem cell markers related to developmental stage of sheep mammary glands. 2080 17

'Cancer stem cells' (CSCs) are tumor cells with stem cell properties hypothesized to be responsible for tumorigenesis, metastatis, and resistance to treatment, and have been identified in different tumors including cutaneous melanoma, using stem cell markers such as CD133. This study explored expression of CD133 and other putative stem cell markers in uveal melanoma. Eight uveal melanoma cell lines were subjected to flow-cytometric (fluorescence-activated cell sorting) analysis of CD133 and other stem cell markers. Eight paraffin-embedded tumors were analyzed by immunohistochemistry for CD133, Pax6, Musashi, nestin, Sox2, ABCB5, and CD68 expressions. Ocular, uveal melanoma, and hematopoietic stem cell distributions of C-terminal and N-terminal CD133 mRNA splice variants were compared by reverse-transcription PCR. Fluorescence-activated cell sorting analysis revealed a population of CD133-positive/nestin-positive cells in cell lines Mel270, OMM 2.3, and OMM2.5. All cell lines studied were positive for nestin, CXCR-4, CD44, and c-kit. Immunohistochemistry identified cells positive for CD133, Pax6, Musashi, nestin, Sox2, ABCB5, and CD68 predominantly at the invading tumor front. C-terminal primers interacting with CD133 splice variant s2 detected a novel variant lacking exon 27. Differential expression of CD133 splice variants was found in iris, ciliary body, retina, and retinal pigment epithelium/choroid as well as in uveal melanoma cell lines. mRNA for nestin, Sox2, and Musashi was present in all studied cell lines. Uveal melanoma such as cutaneous melanoma may therefore contain CSCs. Further experiments are needed to isolate stem cell marker-positive cells, to evaluate their functional properties and to explore therapeutical approaches to these putative CSCs in uveal melanoma.
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PMID:Expression of CD133 and other putative stem cell markers in uveal melanoma. 2190 Jul 92