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The better isolation and detection methods of cranial neural crest stem cells (CNCSC) and the therapeutic potentiality of CNCSC in the treatment of craniofacial abnormalities.

Research Project

Project/Area Number 13357015
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Morphological basic dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

ETO Kazuhiro  Tokyo Medical and Dental University, Section of Molecular Craniofacial Embryology, Professor, 大学院・医歯学総合研究科, 教授 (30014161)

Co-Investigator(Kenkyū-buntansha) OTA Masato  Tokyo Medical and Dental University, Section of Molecular Craniofacial Embryology, Assistant Professor, 大学院・医歯学総合研究科, 助手 (70313228)
ISEKI Sachiko  Tokyo Medical and Dental University, Section of Molecular Craniofacial Embryology, Assistant Professor, 大学院・医歯学総合研究科, 助手 (80251544)
IIMURA Tadahiro  Tokyo Medical and Dental University, Section of Molecular Craniofacial Embryology, Assistant Professor, 大学院・医歯学総合研究科, 助手 (20282775)
IKEDA Masa-aki  Tokyo Medical and Dental University, Section of Molecular Craniofacial Embryology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (20193211)
NAKAHARA Taka  Tokyo Medical and Dental University, Section of Molecular Craniofacial Embryology, Research Associate, 歯学部, 非常勤講師 (10366768)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥50,050,000 (Direct Cost: ¥38,500,000、Indirect Cost: ¥11,550,000)
Fiscal Year 2004: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2003: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2002: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2001: ¥22,230,000 (Direct Cost: ¥17,100,000、Indirect Cost: ¥5,130,000)
KeywordsCranial Neural Crest Cells / Cranial Neural Crest Stem Cells / in situ Tissue Engineering / Cell-based therapy / Cell proliferation / Cell differentiation / Twist / Tissue regeneration / 再生 / 幹細胞 / 細胞分離 / 細胞培養 / 哺乳類頭部神経堤幹細胞 / 頭蓋顔面部の組織再生 / LacZ遺伝子導入マウス / 凍結保存 / DNazyme / 哺乳類頭部神経堤細胞 / 頭部間葉 / 全胚培養 / GFP遺伝子導入マウス / 全胚培養と上顎器官培養
Research Abstract

We tried isolation and isolation of Cranial Neural Crest Stem Cells for the cell-based therapy in the future indicated as below.
1)Identification of the stem cell niche of Neural Crest Cells
a)Distribution pattern of Cranial Neural Crest Cells during Craniofacial morphogenesis in Wnt-1/Cre mouse.
The distribution pattern of Cranial Neural Crest Cells (CNCCs) was examined in Wnt-1/Cre mouse, which indicate b-galactosidase activity in Neural Crest Cells, during craniofacial morphogenesis. B-galactosidase positive CNCCs were identified in the frontal and facial bone, and these pattern were constructed until E9.5.
b)Method for identification of Mesenchymal Stem cells in Craniofacial region by chasing the Label-Retaining Cells (LRCs).
2)Isolation of Cranial Neural Crest Stem Cells (CNCSCs).
a)Modification the isolation methods of CNCSCs
3)Molecular understanding of cell proliferation and apoptosis in cranial neural crest cells
a)Expression pattern of cell-cycle regulators in developing cranial sutu … More re
b)Cell cycle regulation in terminal-differentiated cells in
c)Twist-dependent regulation of cell proliferation and apoptosis
We examined Twist function in CNCCs in Twist null mice and found that Twist is essential for the Cranial nerve patterning, cell growth, and anti-apoptotic activity in CNCCs. We also developed the knockdown methods of Twist activity in vitro by DNazyme and, antisense morpholino nucleotide methods.
d)The transcriptional regulation of cell-cycle regulator E2F1.
e)Cell-cycle related acetylation of the p220/NPAT by CBP histone acetyltransferase
4)Clinical potentialities of Cranial Neural Crest Cells
a)Periodontal tissue regeneration by in situ tissue engineering by the combination of growth factors and scaffolds
b)Periodontal tissue regeneration by in situ tissue engineering by the combination of cell and scaffolds
We examined the clinical potentialities of cranial neural crest cells by tissue engineering methods, and data suggested that they will be a powerful tool in cell-based therapy in the future.
5)Gene expression profiling of the Cranial Neural Crest Stem Cells Less

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (43 results)

All 2004 2003 2002 2001 Other

All Journal Article (27 results) Book (1 results) Publications (15 results)

  • [Journal Article] Twist is required for patterning the cranial nerves and maintaining the viability of mesodermal cells.2004

    • Author(s)
      Ota M.S., Loebel D.A, ORoukeMP, Wong N, Tsoi B, Tam P.P.
    • Journal Title

      Dev Dyn 230

      Pages: 216-228

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In situ tissue engineering of periodontal tissues by seeding with periodontal ligament-derived cells.2004

    • Author(s)
      Nakahara T., Nakamura T, Kobayashi E., Kuremoto K, Matsuno T., Tabata Y, Eto K, Shimizu Y.
    • Journal Title

      Tissue Eng. 10

      Pages: 537-544

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dynamic interaction of p220(NPAT) and CBP/p300 promotes S-phase entry.2004

    • Author(s)
      Wang A., Ikura T., Eto K., Ota M.S.
    • Journal Title

      Biochem Biophys Res Commun. 325

      Pages: 1509-1516

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Twist is required for patterning the cranial nerves and maintaining the viability of mesodermal cells.2004

    • Author(s)
      Ota M.S., Loebel D.A., O'Rourke M.P., Wong N., Tsoi B., Tam P.P.
    • Journal Title

      Dev Dyn 230(2)

      Pages: 216-228

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dynamic interaction of p220 (NPAT) and CBP/p300 promotes S-phase entry.2004

    • Author(s)
      Wang A., Ikura T., Eto K., Ota M.S.
    • Journal Title

      Biochem Biophys Res Commun 325

      Pages: 1509-1516

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In situ tissue engineering of periodontal tissues by seeding with periodontal ligament-derived cells.2004

    • Author(s)
      Nakahara T., Nakamura T., Kobayashi E., Kuremoto K., Matsuno T., Tabata Y, Eto K., Shimizu Y.I
    • Journal Title

      Tissue Eng 10

      Pages: 537-544

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In situ tissue engineering of periodontal tissues by seeding with periodontal ligament-derived cells.2004

    • Author(s)
      Nakahara T., Nakamura T., Kobayashi E., Kuremoto K., Matsuno T., Tabata Y., Eto K., Shimizu Y.
    • Journal Title

      Tissue Eng. 10

      Pages: 537-544

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Dynamic interaction of p220(NPAT) and CBP/p300 promotes S-phase entry.2004

    • Author(s)
      Wang A., Ikura T., Kobayashi E., ETO K., Ota MS.
    • Journal Title

      Biochem Biophys Res Commun. 325・4

      Pages: 1509-1516

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Twist is required for patterning the cranial nerves and maintaining the viability of mesodermal cells.2004

    • Author(s)
      Ota MS., Loebel DA., O'Rourke MP.Wong N., Tsoi B., Tam PP.
    • Journal Title

      Dev.Dyn. 230・2

      Pages: 216-228

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Disappearance of epidermal growth factor receptor is essential in the fusion of the nasal epithelium.2003

    • Author(s)
      Fujino M., Osumi N., Ninomiya Y., Iseki S., Shibasaki Y., Eto K.
    • Journal Title

      Anat.Sci.Int. 78(1)

      Pages: 25-35

    • NAID

      50000771412

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Exposure of neonatal rats to diethylstilbestrol affects the expression of genes involved in ovarian differentiation.2003

    • Author(s)
      Nagai A., Ikeda Y., Aso T., Eto K., Ikeda M.A.
    • Journal Title

      J.Med.Dent.Sci. 50(1)

      Pages: 35-40

    • NAID

      110000076015

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter.2003

    • Author(s)
      Araki K., Nakajima Y., Eto K., Ikeda M.A.
    • Journal Title

      Oncogene. 22(48)

      Pages: 7632-7641

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Role of cyclin D1 cytoplasmic sequestration in the survival of postmitotic neurons.2003

    • Author(s)
      Sumrejkanchanakij P., Tamamori-Adachi M., Matsunaga Y., Eto K., Ikeda M.A.
    • Journal Title

      Oncogene. 22

      Pages: 8723-8730

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of p16(INK4a) in tumors.2003

    • Author(s)
      Auerkari E.I., Suwelo I.S., Tjarta A., Cornain S., Sarwono A.T., Widurini, Joewono, V, Handjari, D.R., Eto, K., Ikeda, M.A.
    • Journal Title

      Oral Oncology. 9

      Pages: 241-246

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] DNazyme-mediated cleavage of Twist transcripts and increase in cellular apoptosis.2003

    • Author(s)
      Hjiantoniou E., Iseki S., Uney J.B., Phylactou L.A.
    • Journal Title

      Biochem.Biophys.Res.Commun. 300

      Pages: 178-181

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel approach to regeneration of periodontal tissues based on in situ tissue engineering : Effects of controlled release of basic fibroblast growth factor from a sandwich membrane.2003

    • Author(s)
      Nakahara T., Kobayashi E., Shigeno K., Eto K., Shimizu Y.
    • Journal Title

      Tissue Engineering 9

      Pages: 153-162

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mouse GLl3 Regulates Fgf8 Expression and Apoptosis in the Developing Neural Tube, Face, and Limb Bud.2002

    • Author(s)
      Aoto K., Nishimura T., Eto K., Motoyama J.
    • Journal Title

      Dev.Biol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Phosphate depletion enhances bone morphogenetic protein-4 gene expression in a cultured mouse marrow stromal cell line ST2.2002

    • Author(s)
      Goseki-Sone M, Yamada A, Hamatani R, Mizoi L, Iimura T, Ezawa I.
    • Journal Title

      Biochem Biophys Res Commun 299

      Pages: 395-399

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Synergistic effect of fibroblast growth factor-4 in ectopic bone formation induced by bone morphogenetic protein-2.2002

    • Author(s)
      Kubota K, Iseki S, Kuroda S, Oida S, Iimura T, Duarte WR, Ohya K, Ishikawa I, Kasugai S.
    • Journal Title

      Bone 31

      Pages: 465-471

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effect of swimming on cartilage formation.2002

    • Author(s)
      Yamada A., Maruoka Y., Asahi K, Iimura T., Oida S., Ezawa I., Goseki-Sone M.A
    • Journal Title

      J Nutr Sci Vitaminol 48

      Pages: 238-241

    • NAID

      50000585333

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Onset of the segmentation clock in the chick embryo : evidence for oscillations in the somite precursors in the primitive streak.2002

    • Author(s)
      Jouve C., Iimura T., Pourquie O.
    • Journal Title

      Development 129

      Pages: 1107-1117

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tissue origins and interactions in the mammalian skull vault.2002

    • Author(s)
      Jiang X., Iseki S., Maxson R.E., Sucov H.M., Morriss-Kay G.M.
    • Journal Title

      Dev.Biol. 241

      Pages: 106-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Study of Fibroblast Growth Factor Receptor Signaling during Skull Vault Development by Ex-Utero Surgery.2001

    • Author(s)
      Iseki S., Morriss-Kay G.M., Eto K.
    • Journal Title

      J.Hard Tissue Biology 10

      Pages: 25-29

    • NAID

      110001142353

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of the curly tail genotype on neuroepithelial integrity and cell proliferation during late stages of primary neurulation.2001

    • Author(s)
      Hall M., Gofflot F., Iseki S., Morriss-Kay G.M.
    • Journal Title

      J.Anat 199

      Pages: 645-655

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genetic control of the cell pro-liferation-differentiation balance in the developing skull vault : roles of fibroblast growth factor receptor signaling pathways.2001

    • Author(s)
      Morriss-Kay G.M., Iseki S., Johnson D.
    • Journal Title

      The Molecular Basis of Skeletogenesis (ed.J.Goode) Novartis Fund Symp. 232

      Pages: 102-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Development and cell dynamics of PLCb2 cells in mouse taste buds.

    • Author(s)
      Yamada Y.
    • Journal Title

      J.Stmatol.Soc In press

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Twist is involved in establishment of the coronal suture.

    • Author(s)
      Yoshida T., Phylactou LA., Uney JB., Ishikawa I., Eto K., Iseki S.
    • Journal Title

      J.Anatomy In press

    • Related Report
      2004 Annual Research Report
  • [Book] 歯の健康学2004

    • Author(s)
      江藤 一洋 編
    • Total Pages
      203
    • Publisher
      岩波新書
    • Related Report
      2004 Annual Research Report
  • [Publications] Fujino M. et al.: "Disappearance of epidermal growth factor receptor is essential in the fusion of the nasal epithelium."Anat.Sci.Int.. 78(1). 25-35 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hijantoniou E. et al.: "DNazyme-mediated cleavage of Twist transcripts and increase in cellular apoptosis."Biochem.Biophys.Res.Commun.. 178-181 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ota M.S.et al.: "Twist is required for patterning the cranial nerves and maintaining the viability of mesodermal cells."Dev.Dynam.. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] 井関 祥子: "細胞周期関連分子の局在によるマウス胎児頭蓋冠縫合部における細胞増殖と分化の検討"炎症再生. 23(1). 29-33 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 井関 祥子: "哺乳類の発生学-着床初期および器官形成期中期"小児外科学. 35(3). 368-347 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Aoto K., Nishimura T., Eto K., Motoyama J: "Mouse GLI3 Regulates Fgf8 Expression and Apoptosis in the Developing NeruralTube. Face. and Limb Bud"Developmental Biology. 251. 320-332 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kubota K, Iseki S, Kuroda S, Oida S, Iimura T, Duarte WR, Ohya K, Ishikawa I, Kasugai S.: "Synergistic effect of fibroblast growth factor-4 in ectopic bone formation in-duced by bone morphogenetic protein-2"Bone. 31. 465-471 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakahara T, Nakamura T, Kobayashi E, Inoue M, Shigeno K, Tabata Y, Eto K., Shimizu Y.: "Novel approach to regeneration of periodontal tissues based on in situ tissue engineering : effects of controlled release of basic fibroblast growth factor from a sandwich membrane"Tissue Engineering. 9・1. 153-162 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujino M., Osumi N., Ninomiya Y., Iseki S., Shibasaki Y., Eto K.: "Disappearance of epidermal growth factor receotor is essential in fusion of the nasal epithelium"Anatomical Science International. 78. 25-35 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 井関祥子, 野地澄晴: "FGFシステムと骨パターン形成"実験医学増刊「最新の骨研究に迫る」. 20. 107-112 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中原 貴, 中村達郎, 田畑泰彦, 江藤一洋, 清水慶彦: "In situ Tissue Engineeringによる歯周組織の再生"炎症・再生. 23・2. 116-121 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kouki T, Imai H, Aoto K, Eto K, Shioda S, Kawamura K, Kikuyama S.: "Developmental origin of the rat adenohypophysis prior to the formation of Rathke's pouch"Development. 128(6). 959-963 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hall M, Gofflot F, Iseki S, Morriss-Kay GM.: "Effects of the curly tail genotype on neuroepithelial integrity and cell proliferation during late stages of primary neurulation"Journal of anatomy. 199. 645-655 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hall M, Gofflot F, Iseki S, Morriss-Kay GM.: "Tissue origins and interactions in the mammalian skull vault"Developmental Biology. 241. 106-116 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 丸山征郎, 山村研一, 柳雄介編(分担:今井元, 太田正人, 江藤一洋): "発生・再生と医学-阿蘇シンポジウム2000-"南山堂. 115 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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