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PMID: 15923633 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Combination of hTERT and bmi-1, E6, or E7 induces prolongation of the life span of bone marrow stromal cells from an elderly donor without affecting their neurogenic potential.

Molecular and cellular biology ·Vol. 25 ·No. 12 ·2005-06-00 ·Pages 5183-95

Mori T, Kiyono T, Imabayashi H, Takeda Y, Tsuchiya K, Miyoshi S, Makino H, Matsumoto K, Saito H, Ogawa S, Sakamoto M, Hata J, Umezawa A

Abstract

Murine bone marrow stromal cells differentiate not only into mesodermal derivatives, such as osteocytes, chondrocytes, adipocytes, skeletal myocytes, and cardiomyocytes, but also into neuroectodermal cells in vitro. Human bone marrow stromal cells are easy to isolate but difficult to study because of their limited life span. To overcome this problem, we attempted to prolong the life span of bone marrow stromal cells and investigated whether bone marrow stromal cells modified with bmi-1, hTERT, E6, and E7 retained their differentiated capability, or multipotency. In this study, we demonstrated that the life span of bone marrow stromal cells derived from a 91-year-old donor could be extended and that the stromal cells with an extended life span differentiated into neuronal cells in vitro. We examined the neuronally differentiated cells morphologically, physiologically, and biologically and compared the gene profiles of undifferentiated and differentiated cells. The neuronally differentiated cells exhibited characteristics similar to those of midbrain neuronal progenitors. Thus, the results of this study support the possible use of autologous-cell graft systems to treat central nervous system diseases in geriatric patients.

MeSH Terms
Aged Aged, 80 and over Animals Bone Marrow Cells/cytology,physiology Calcium/metabolism Cell Cycle Proteins/genetics,metabolism Cell Differentiation/physiology Cell Lineage Cells, Cultured DNA-Binding Proteins Female Gene Expression Profiling Gene Expression Regulation Humans Karyotyping Mice Multipotent Stem Cells/cytology,physiology Neurons/cytology,physiology Nuclear Proteins/genetics,metabolism Oligonucleotide Array Sequence Analysis Oncogene Proteins, Viral/genetics,metabolism Polycomb Repressive Complex 1 Proto-Oncogene Proteins/genetics,metabolism Repressor Proteins/genetics,metabolism Stromal Cells/cytology,physiology Telomerase/genetics,metabolism Telomere/metabolism
Chemicals
Bmi1 protein, mouse Cell Cycle Proteins DNA-Binding Proteins Nuclear Proteins Oncogene Proteins, Viral Proto-Oncogene Proteins Repressor Proteins Polycomb Repressive Complex 1 Telomerase Calcium
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Mori Taisuke
Department of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
Kiyono Tohru
Imabayashi Hideaki
Takeda Yukiji
Tsuchiya Kohei
Miyoshi Shunichirou
Makino Hatsune
Matsumoto Kenji
Saito Hirohisa
Ogawa Satoshi
Sakamoto Michiie
Hata Jun-Ichi
Umezawa Akihiro
References (39)
39 references, click to expand
  1. Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF.
    Genes Dev. 1999 Oct 15;13(20):2678-90 PMID: 10541554
  2. Extension of life-span by introduction of telomerase into normal human cells.
    Science. 1998 Jan 16;279(5349):349-52 PMID: 9454332
  3. Inhibition of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression reduces dopaminergic sprouting in the injured striatum.
    Eur J Neurosci. 2000 Oct;12(10):3462-8 PMID: 11029615
  4. Bone development.
    Annu Rev Cell Dev Biol. 2000;16:191-220 PMID: 11031235
  5. From marrow to brain: expression of neuronal phenotypes in adult mice.
    Science. 2000 Dec 1;290(5497):1775-9 PMID: 11099418
  6. EAT/mcl-1 expression in the human embryonal carcinoma cells undergoing differentiation or apoptosis.
    Exp Cell Res. 2001 May 15;266(1):114-25 PMID: 11339830
  7. Interactions between fibroblast growth factors and Notch regulate neuronal differentiation.
    J Neurosci. 2001 Aug 1;21(15):5587-96 PMID: 11466430
  8. Brain from bone: efficient "meta-differentiation" of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent.
    Differentiation. 2001 Oct;68(4-5):235-44 PMID: 11776476
  9. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease.
    Nature. 2002 Jul 4;418(6893):50-6 PMID: 12077607
  10. Clonal heterogeneity in differentiation potential of immortalized human mesenchymal stem cells.
    Biochem Biophys Res Commun. 2002 Jul 12;295(2):354-61 PMID: 12150956
  11. The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells.
    Cancer Res. 2002 Aug 15;62(16):4736-45 PMID: 12183433
  12. Use of isolated mature osteoblasts in abundance acts as desired-shaped bone regeneration in combination with a modified poly-DL-lactic-co-glycolic acid (PLGA)-collagen sponge.
    J Cell Physiol. 2003 Jan;194(1):45-53 PMID: 12447988
  13. Mutations in NR4A2 associated with familial Parkinson disease.
    Nat Genet. 2003 Jan;33(1):85-9 PMID: 12496759
  14. The constitutive and inducible expression of Nurr1, a key regulator of dopaminergic neuronal differentiation, in human neural and non-neural cell lines.
    Neuropathology. 2002 Dec;22(4):219-32 PMID: 12564761
  15. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
    Nature. 2003 May 15;423(6937):302-5 PMID: 12714971
  16. Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis.
    Exp Cell Res. 2003 Aug 1;288(1):35-50 PMID: 12878157
  17. Induction of growth arrest and cell death by overexpression of the cyclin-Cdk inhibitor p21 in hamster BHK21 cells.
    Oncogene. 1998 Jan 22;16(3):369-80 PMID: 9467962
  18. Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells.
    Nature. 1998 Nov 5;396(6706):84-8 PMID: 9817205
  19. The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus.
    Nature. 1999 Jan 14;397(6715):164-8 PMID: 9923679
  20. Expression of EGF receptor and FGF receptor isoforms during neuroepithelial stem cell differentiation.
    J Neurobiol. 1999 Feb 5;38(2):207-24 PMID: 10022567
  21. Cardiomyocytes can be generated from marrow stromal cells in vitro.
    J Clin Invest. 1999 Mar;103(5):697-705 PMID: 10074487
  22. The Notch-Hes pathway in mammalian neural development.
    Cell Res. 1999 Sep;9(3):179-88 PMID: 10520600
  23. Immortalization of human fetal cells: the life span of umbilical cord blood-derived cells can be prolonged without manipulating p16INK4a/RB braking pathway.
    Mol Biol Cell. 2005 Mar;16(3):1491-9 PMID: 15647378
  24. In vivo cardiovasculogenesis by direct injection of isolated adult mesenchymal stem cells.
    Exp Cell Res. 2003 Aug 1;288(1):51-9 PMID: 12878158
  25. Differentiation potential of a mouse bone marrow stromal cell line.
    J Cell Biochem. 2003 Sep 1;90(1):158-69 PMID: 12938165
  26. Neuroectodermal differentiation from mouse multipotent adult progenitor cells.
    Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11854-60 PMID: 12925733
  27. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.
    Science. 2003 Oct 17;302(5644):415-9 PMID: 14564000
  28. Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a.
    Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12747-52 PMID: 14557550
  29. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation.
    Nature. 2003 Oct 30;425(6961):962-7 PMID: 14574365
  30. Comprehensive transcriptome analysis of differentiation of embryonic stem cells into midbrain and hindbrain neurons.
    Dev Biol. 2004 Jan 15;265(2):491-501 PMID: 14732407
  31. Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging.
    Cell. 1991 May 31;65(5):737-52 PMID: 1904008
  32. Targeted degradation of the retinoblastoma protein by human papillomavirus E7-E6 fusion proteins.
    EMBO J. 1992 Jul;11(7):2425-31 PMID: 1321031
  33. Telomere length predicts replicative capacity of human fibroblasts.
    Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10114-8 PMID: 1438199
  34. The two-stage mechanism controlling cellular senescence and immortalization.
    Exp Gerontol. 1992 Jul-Aug;27(4):383-9 PMID: 1333985
  35. Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination.
    J Neurosci Res. 1993 Aug 1;35(5):567-76 PMID: 8377226
  36. Epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and basic fibroblast growth factor (bFGF) differentially influence neural precursor cells of mouse embryonic mesencephalon.
    J Neurosci Res. 1995 Oct 1;42(2):172-83 PMID: 8568917
  37. Dopamine neuron agenesis in Nurr1-deficient mice.
    Science. 1997 Apr 11;276(5310):248-50 PMID: 9092472
  38. Spectral karyotyping refines cytogenetic diagnostics of constitutional chromosomal abnormalities.
    Hum Genet. 1997 Dec;101(3):255-62 PMID: 9439652
  39. The bHLH gene Hes1 regulates differentiation of multiple cell types.
    Mol Cells. 2000 Feb 29;10(1):1-7 PMID: 10774739
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
2005-06-00
Pages
5183-95
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1140572
Subset
IM
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