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Journal ArticleDOI

Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion

04 Apr 2002-Nature (Nature Publishing Group)-Vol. 416, Iss: 6880, pp 542-545
TL;DR: It is demonstrated that mouse bone marrow cells can fuse spontaneously with embryonic stem cells in culture in vitro that contains interleukin-3, which, without detailed genetic analysis, might be interpreted as ‘dedifferentiation’ or transdifferentiation.
Abstract: Recent studies have demonstrated that transplanted bone marrow cells can turn into unexpected lineages including myocytes, hepatocytes, neurons and many others. A potential problem, however, is that reports discussing such 'transdifferentiation' in vivo tend to conclude donor origin of transdifferentiated cells on the basis of the existence of donor-specific genes such as Y-chromosome markers. Here we demonstrate that mouse bone marrow cells can fuse spontaneously with embryonic stem cells in culture in vitro that contains interleukin-3. Moreover, spontaneously fused bone marrow cells can subsequently adopt the phenotype of the recipient cells, which, without detailed genetic analysis, might be interpreted as 'dedifferentiation' or transdifferentiation.
Citations
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Journal ArticleDOI
04 Jul 2002-Nature
TL;DR: It is reported here that cells co-purifying with mesenchymal stem cells—termed here multipotent adult progenitor cells or MAPCs—differentiate, at the single cell level, not only into meschymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro.
Abstract: We report here that cells co-purifying with mesenchymal stem cells--termed here multipotent adult progenitor cells or MAPCs--differentiate, at the single cell level, not only into mesenchymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro. When injected into an early blastocyst, single MAPCs contribute to most, if not all, somatic cell types. On transplantation into a non-irradiated host, MAPCs engraft and differentiate to the haematopoietic lineage, in addition to the epithelium of liver, lung and gut. Engraftment in the haematopoietic system as well as the gastrointestinal tract is increased when MAPCs are transplanted in a minimally irradiated host. As MAPCs proliferate extensively without obvious senescence or loss of differentiation potential, they may be an ideal cell source for therapy of inherited or degenerative diseases.

5,475 citations

Journal ArticleDOI
TL;DR: It is shown that a naturally exfoliated human organ contains a population of stem cells that are completely different from previously identified stem cells, which may be an unexpected unique resource for stem-cell therapies including autologous stem- cell transplantation and tissue engineering.
Abstract: To isolate high-quality human postnatal stem cells from accessible resources is an important goal for stem-cell research. In this study we found that exfoliated human deciduous tooth contains multipotent stem cells [stem cells from human exfoliated deciduous teeth (SHED)]. SHED were identified to be a population of highly proliferative, clonogenic cells capable of differentiating into a variety of cell types including neural cells, adipocytes, and odontoblasts. After in vivo transplantation, SHED were found to be able to induce bone formation, generate dentin, and survive in mouse brain along with expression of neural markers. Here we show that a naturally exfoliated human organ contains a population of stem cells that are completely different from previously identified stem cells. SHED are not only derived from a very accessible tissue resource but are also capable of providing enough cells for potential clinical application. Thus, exfoliated teeth may be an unexpected unique resource for stem-cell therapies including autologous stem-cell transplantation and tissue engineering.

2,633 citations

Journal ArticleDOI
18 Oct 2002-Science
TL;DR: The transcriptional profiles of mouse embryonic, neural, and hematopoietic stem cells were compared to define a genetic program for stem cells and provide a foundation for a more detailed understanding of stem cell biology.
Abstract: The transcriptional profiles of mouse embryonic, neural, and hematopoietic stem cells were compared to define a genetic program for stem cells. A total of 216 genes are enriched in all three types of stem cells, and several of these genes are clustered in the genome. When compared to differentiated cell types, stem cells express a significantly higher number of genes (represented by expressed sequence tags) whose functions are unknown. Embryonic and neural stem cells have many similarities at the transcriptional level. These results provide a foundation for a more detailed understanding of stem cell biology.

1,776 citations

Journal ArticleDOI
09 Aug 2002-Cell
TL;DR: It is shown that developmentally relevant signaling factors can induce mouse embryonic stem cells to differentiate into spinal progenitor cells, and subsequently into motor neurons, through a pathway recapitulating that used in vivo.

1,763 citations


Cites background from "Bone marrow cells adopt the phenoty..."

  • ...Analysis of the Certain cell populations have been reported to undergo fusion with somatic cells (Terada et al., 2002; Ying pattern of peripheral projections of eGFP motor axons in stage 27 embryos revealed that HBG3 ES cell-derived et al., 2002) prompting us to test the possibility that HBG3 ES cell-derived eGFP /HB9 MNs might have MNs grafted at rostral cervical levels projected to axial musculature (data not shown), MNs grafted at thoracic formed somatic hybrids with chick neurons....

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  • ...…progenitor cells derived from of MNs (Renoncourt et al., 1998), but neither the pathwayother tissues and organs (Brazelton et al., 2000; Mezey of generation of these neurons nor their developmentalet al., 2000; Terada et al., 2002; Ying et al., 2002), and potential in vivo have been explored....

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  • ..., 1998), but neither the pathway other tissues and organs (Brazelton et al., 2000; Mezey of generation of these neurons nor their developmental et al., 2000; Terada et al., 2002; Ying et al., 2002), and potential in vivo have been explored....

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  • ...Analysis of theCertain cell populations have been reported to un- dergo fusion with somatic cells (Terada et al., 2002; Ying pattern of peripheral projections of eGFP motor axons in stage 27 embryos revealed that HBG3 ES cell-derivedet al., 2002) prompting us to test the possibility that HBG3 ES…...

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Journal ArticleDOI
08 Apr 2004-Nature
TL;DR: The data suggest that even in the microenvironment of the injured heart, c-kit-enriched BM cells, Lin- c- Kit+ BM cells and c-Kit+ Thy1.1lo Lin- Sca-1+ long-term reconstituting haematopoietic stem cells adopt only traditional haem atopoetic fates.
Abstract: Under conditions of tissue injury, myocardial replication and regeneration have been reported. A growing number of investigators have implicated adult bone marrow (BM) in this process, suggesting that marrow serves as a reservoir for cardiac precursor cells. It remains unclear which BM cell(s) can contribute to myocardium, and whether they do so by transdifferentiation or cell fusion. Here, we studied the ability of c-kit-enriched BM cells, Lin- c-kit+ BM cells and c-kit+ Thy1.1(lo) Lin- Sca-1+ long-term reconstituting haematopoietic stem cells to regenerate myocardium in an infarct model. Cells were isolated from transgenic mice expressing green fluorescent protein (GFP) and injected directly into ischaemic myocardium of wild-type mice. Abundant GFP+ cells were detected in the myocardium after 10 days, but by 30 days, few cells were detectable. These GFP+ cells did not express cardiac tissue-specific markers, but rather, most of them expressed the haematopoietic marker CD45 and myeloid marker Gr-1. We also studied the role of circulating cells in the repair of ischaemic myocardium using GFP+-GFP- parabiotic mice. Again, we found no evidence of myocardial regeneration from blood-borne partner-derived cells. Our data suggest that even in the microenvironment of the injured heart, c-kit-enriched BM cells, Lin- c-kit+ BM cells and c-kit+ Thy1.1(lo) Lin- Sca-1+ long-term reconstituting haematopoietic stem cells adopt only traditional haematopoietic fates.

1,748 citations

References
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Journal ArticleDOI
02 Apr 1999-Science
TL;DR: Adult stem cells isolated from marrow aspirates of volunteer donors could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages.
Abstract: Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

20,479 citations


"Bone marrow cells adopt the phenoty..." refers background in this paper

  • ...Bone marrow contains haematopoietic stem cells producing all the blood cells, and mesenchymal stem cell...

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Journal ArticleDOI
27 Feb 1997-Nature
TL;DR: The birth of lambs from differentiated fetal and adult cells confirms that differentiation of that cell did not involve the irreversible modification of genetic material required for development to term and reinforces previous speculation that by inducing donor cells to become quiescent it will be possible to obtain normal development from a wide variety of differentiated cells.
Abstract: Fertilization of mammalian eggs is followed by successive cell divisions and progressive differentiation, first into the early embryo and subsequently into all of the cell types that make up the adult animal. Transfer of a single nucleus at a specific stage of development, to an enucleated unfertilized egg, provided an opportunity to investigate whether cellular differentiation to that stage involved irreversible genetic modification. The first offspring to develop from a differentiated cell were born after nuclear transfer from an embryo-derived cell line that had been induced to become quiescent. Using the same procedure, we now report the birth of live lambs from three new cell populations established from adult mammary gland, fetus and embryo. The fact that a lamb was derived from an adult cell confirms that differentiation of that cell did not involve the irreversible modification of genetic material required for development to term. The birth of lambs from differentiated fetal and adult cells also reinforces previous speculation that by inducing donor cells to become quiescent it will be possible to obtain normal development from a wide variety of differentiated cells.

4,721 citations


"Bone marrow cells adopt the phenoty..." refers background in this paper

  • ...The transferred nuclei from adult cells could be reprogrammed by a factor or factors in the cytoplasm of oocytes, showing the same potential for normal animal development as early embryonic nucle...

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Journal ArticleDOI
30 Oct 1998-Cell
TL;DR: It is reported that the activity of Oct4 is essential for the identity of the pluripotential founder cell population in the mammalian embryo and also determines paracrine growth factor signaling from stem cells to the trophectoderm.

3,461 citations


"Bone marrow cells adopt the phenoty..." refers background in this paper

  • ...Oct3/4 and UTF1, markers of undifferentiated embryonic stem cell...

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Journal ArticleDOI
06 Mar 1998-Science
TL;DR: Transplantation of genetically marked bone marrow into immunodeficient mice revealed that marrow-derived cells migrate into areas of induced muscle degeneration, undergo myogenic differentiation, and participate in the regeneration of the damaged fibers.
Abstract: Growth and repair of skeletal muscle are normally mediated by the satellite cells that surround muscle fibers. In regenerating muscle, however, the number of myogenic precursors exceeds that of resident satellite cells, implying migration or recruitment of undifferentiated progenitors from other sources. Transplantation of genetically marked bone marrow into immunodeficient mice revealed that marrow-derived cells migrate into areas of induced muscle degeneration, undergo myogenic differentiation, and participate in the regeneration of the damaged fibers. Genetically modified, marrow-derived myogenic progenitors could potentially be used to target therapeutic genes to muscle tissue, providing an alternative strategy for treatment of muscular dystrophies.

2,881 citations


"Bone marrow cells adopt the phenoty..." refers background in this paper

  • ...Moreover, transplantation of adult bone marrow cells has generated unexpected phenotypes in vivo , including muscle cell...

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Journal ArticleDOI
04 May 2001-Cell
TL;DR: It is shown that rare cells that home to bone marrow can LTR primary and secondary recipients, and this finding may contribute to clinical treatment of genetic disease or tissue repair.

2,773 citations

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