Nucleostemin Is a Marker of Proliferating Stromal Stem Cells in Adult Human Bone Marrow

Kafienah, Wáel; Mistry, Sanjay; Williams, Christopher; Hollander, Anthony P.

doi:10.1634/stemcells.2005-0416

Cited by 105 publications

(103 citation statements)

References 35 publications

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“…Besides the bone marrow, adult stem cells have been isolated from a variety of tissues, such as the liver, nerve, muscle, skin, synovium and cartilage. 33,34 Recent studies have shown that extracted non-decayed impacted third molar tooth germ tissues could serve as a very valuable source of stem cells. As these tissues are removed during standard prophylactic interventions and do not require additional surgical procedures, utilization of such resources to isolate stem cells offers an attractive alternative.…”

Section: Discussionmentioning

confidence: 99%

“…Real-time PCR analysis revealed that hTGSCs present undifferentiated cell markers such as nucleo-stemin and human telomerase reverse-transcriptase, indicating that these cells are in an undifferentiated, proliferative state. 34 Although hTGSCs were proliferative, the expression of oct4 decreased gradually as the passage number increased. As oct4 is crucial for the maintenance of the pluri-potency, 35 decrease in oct4 in subsequent passages might indicate the loss of differentiation capacity of hTGSCs and potential senescence.…”

Section: Figurementioning

confidence: 99%

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Isolation and characterization of stem cells derived from human third molar tooth germs of young adults: implications in neo-vascularization, osteo-, adipo- and neurogenesis

et al. 2009

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A number of studies have reported in the last decade that human tooth germs contain multipotent cells that give rise to dental and peri-odontal structures. The dental pulp, third molars in particular, have been shown to be a significant stem cell source. In this study, we isolated and characterized human tooth germ stem cells (hTGSCs) from third molars and assessed the expression of developmentally important transcription factors, such as oct4, sox2, klf4, nanog and c-myc, to determine their pluri-potency. Flowcytometry analysis revealed that hTGSCs were positive for CD73, CD90, CD105 and CD166, but negative for CD34, CD45 and CD133, suggesting that these cells are mesenchymal-like stem cells. Under specific culture conditions, hTGSCs differentiated into osteogenic, adipogenic and neurogenic cells, as well as formed tube-like structures in Matrigel assay. hTGSCs showed significant levels of expression of sox2 and c-myc messenger RNA (mRNA), and a very high level of expression of klf4 mRNA when compared with human embryonic stem cells. This study reports for the first time that hTGSCs express developmentally important transcription factors that could render hTGSCs an attractive candidate for future somatic cell re-programming studies to differentiate germs into various tissue types, such as neurons and vascular structures. In addition, these multipotential hTGSCs could be important stem cell sources for autologous transplantation.

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Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Isolation and characterization of stem cells derived from human third molar tooth germs of young adults: implications in neo-vascularization, osteo-, adipo- and neurogenesis

et al. 2009

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“…High levels of nucleostemin expression are also detected in several types of cancer cells [16][17][18]. Although the role of nucleostemin in U2OS human osteosarcoma cells has been assessed extensively by siRNA-mediated knockdown experiments, the physiological function of nucleostemin in stem cells has been little characterized, with the exception of a few studies [15,45]. Here, we assessed the roles of nucleostemin in ES cells and ES cell-derived neural stem cells.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it is generally assumed that nucleostemin plays an important role in stem cell proliferation. However, with the exception of a few studies using stromal stem cells from adult human bone marrow [15], most studies investigating nucleostemin function have been performed using nonstem cells, such as U2OS osteosarcoma cells [16][17][18]. The role of nucleostemin in stem cells is therefore still unclear.…”

Section: Introductionmentioning

confidence: 99%

Differential Requirement for Nucleostemin in Embryonic Stem Cell and Neural Stem Cell Viability

et al. 2009

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Stem cells have the remarkable ability to self-renew and to generate multiple cell types. Nucleostemin is one of proteins that are enriched in many types of stem cells. Targeted deletion of nucleostemin in the mouse results in developmental arrest at the implantation stage, indicating that nucleostemin is crucial for early embryogenesis. However, the molecular basis of nucleostemin function in early mouse embryos remains largely unknown, and the role of nucleostemin in tissue stem cells has not been examined by gene targeting analyses due to the early embryonic lethality of nucleostemin null animals. To address these questions, we generated inducible nucleostemin null embryonic stem (ES) cells in which both alleles of nucleostemin are disrupted, but nucleostemin cDNA under the control of a tetracycline-responsive transcriptional activator is introduced into the Rosa26 locus. We show that loss of nucleostemin results in reduced cell proliferation and increased apoptosis in both ES cells and ES cell-derived neural stem/progenitor cells. The reduction in cell viability is much more profound in ES cells than in neural stem/progenitor cells, an effect that is mediated at least in part by increased induction and accumulation of p53 and/or activated caspase-3 in ES cells than in neural stem/progenitor cells.

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“…The lack of expression of these pluripotency markers in intact patellar tendon suggested that immunohistochemical staining of these markers was not suitable for the detection of tendon stem cell in intact tendon in situ. The activation of Oct4, Nanog, Sox2, and nucleostemin as well as CD146 after tendon injury might be related to the functions of these proteins in regulating self-renewal, cell proliferation, differentiation, and/or angiogenesis [28][29][30][31][32].…”

Section: Role Of Lrcs During Tendon Repairmentioning

confidence: 99%

In Vivo Identity of Tendon Stem Cells and the Roles of Stem Cells in Tendon Healing

Tan

Lui

Lee

2013

Stem Cells and Development

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We investigated the spatial distribution of stem cells in tendons and the roles of stem cells in early tendon repair. The relationship between tendon-derived stem cells (TDSCs) isolated in vitro and tendon stem cells in vivo was also explored. Iododeoxyuridine (IdU) label-retaining method was used for labeling stem cells in rat patellar tendons with and without injury. Co-localization of label-retaining cells (LRCs) with different markers was done by immunofluorescent staining. TDSCs were isolated from patellar tendon mid-substance after IdU pulsing, and the expression of different markers in fresh and expanded cells was done by immunofluorescent staining. More LRCs were found at the peritenon and tendon-bone junction compared with the mid-substance. Some LRCs at the peritenon were located at the perivascular niche. The LRC number and the expression of proliferative, tendon-related, pluripotency, and pericyte-related markers in LRCs in the window wound increased. Most of the freshly isolated TDSCs expressed IdU, and some TDSCs expressed pericyte-related markers, which were lost during expansion. Both freshly isolated and subcultured TDSCs expressed pluripotency markers, which were absent in LRCs in intact tendons. In conclusion, we identified LRCs at the peritenon, mid-substance, and tendon-bone junction. There were both vascular and non-vascular sources of LRCs at the peritenon, while the source of LRCs at the mid-substance was non-vascular. LRCs participated in tendon repair via migration, proliferation, activation for tenogenesis, and increased pluripotency. Some LRCs in the window wound were pericyte like. Most of the mid-substance TDSCs were LRCs. The pluripotency markers and pericyte-related marker in LRCs might be important for function after injury. Recently, stem/progenitor cells have been isolated from tendon tissues of varies species, including human, horse, rabbit, rat, and mouse [3][4][5][6]. These stem/progenitor cells isolated from tendon tissues exhibited self-renewal and multilineage differentiation potential [3][4][5][6]. Since the origin and identity of these cells were not clear, we called them tendon-derived stem cells (TDSCs) to indicate only the tissue from which the cells were isolated [5].Many studies suggested that the wall of capillaries, small vessels, and large vessels harbored stem/progenitor cells [7][8][9][10][11]. Some studies further suggested that mesenchymal stem cells (MSCs) were derived from pericytes [9,12].Pericytes/perivascular cells from a variety of tissues were reported to exhibit characteristics that were strikingly similar to those of MSCs [7][8][9][10][11]. For tendons, there was also evidence that the vasculature of tendon tissue might harbor stem cells [13]. However, tendon mid-substance is hypovascular compared with other tissues and receives its blood supply mainly from the endotenon and paratenon [14]. TDSCs isolated from the tendon mid-substance, while positive for alpha smooth muscle actin [5], were not positive for other pericyte-related markers [3,15]. Tend...

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Nucleostemin Is a Marker of Proliferating Stromal Stem Cells in Adult Human Bone Marrow

Cited by 105 publications

References 35 publications

Isolation and characterization of stem cells derived from human third molar tooth germs of young adults: implications in neo-vascularization, osteo-, adipo- and neurogenesis

Isolation and characterization of stem cells derived from human third molar tooth germs of young adults: implications in neo-vascularization, osteo-, adipo- and neurogenesis

Differential Requirement for Nucleostemin in Embryonic Stem Cell and Neural Stem Cell Viability

In Vivo Identity of Tendon Stem Cells and the Roles of Stem Cells in Tendon Healing

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