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再生医療・細胞移植に対する病理学的な評価システムの確立

Research Project

Project/Area Number 14657051
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Human pathology
Research InstitutionNational Research Institute for Child Health and Development

Principal Investigator

梅澤 明弘  国立成育医療センター研究所, 部長 (70213486)

Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Keywords細胞移植 / 再生医療 / 形質転換 / 間葉系細胞 / 骨髄間質 / 遺伝子導入 / 寿命延長 / 生体内マイクロデバイス / 病理学 / 幹細胞 / 評価システム / 細胞治療 / 心筋細胞 / ヒト骨髄間質細胞
Research Abstract

再生医療において移植細胞の生体内での局在を検出するシステムはいまだ確立されていない.移植細胞源として期待される骨髄間質細胞を生体外にて超常磁性体酸化鉄(SPIO)でラベルした後、モデル動物へ移植しMRIによる追跡が可能か否かを検討した.方法として、ヒト骨髄より採取した骨髄間質細胞を用い、SPIOであるResovistを培養液に添加し、細胞内への導入を行った.ラベル細胞の造影効果はNMR spectrometerにてT2緩和時間を測定した.ラベル細胞を免疫不全マウスの大腿部筋層内に注入し、T2-weighted fast spin-echoにてMRイメージングを行うとともに組織像との比較を行った.Resovist導入開始24時間で98%の細胞に鉄染色陽性を確認し、spectrometerにて細胞量に依存したT2短縮効果を認めた.移植後はT2強調像にて移植部位に境界明瞭な低信号領域が描出され、組織学的にも同領域に生存する移植細胞の局在を確認した.低信号領域は移植後8週にても描出されていたが、組織学的には移植後2週以降、宿主由来と思われる鉄染色強陽性細胞の増加が見られ、MRI画像が正確に移植細胞を反映しているとは言えなかった.以上のことより、結論として生体内外において細胞に導入されたSPIOの造影効果が維持され、MR画像にて描出できることが明らかになった.マウス移植モデルにおいては、MR信号減弱が移植細胞由来であると判断できるのは1週以内であったが、移植初期の細胞局在を確認するシステムとしては有効であることが明らかになったことは、「再生医療・細胞移植に対する病理学的な評価システムの確立」にとって極めて重要な意味があると考える.

Report

(3 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (33 results)

All 2005 Other

All Journal Article (2 results) Publications (31 results)

  • [Journal Article] Combination of hTERT and Bmi-1, E6 or E7 induce prolongation of the life span of bone marrow stromal cells from an elderly donor without affecting their neurogenic potential.2005

    • Author(s)
      Mori, T., Kiyono, et al.
    • Journal Title

      Mol Cell Biol in press,

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Immortalization of human fetal cells: The life span of umbilical-cord-blood-derived cells can be prolonged without manipulating p16INK4a/RB braking pathway.2005

    • Author(s)
      Terai, M., Uyama, T., Sugiki, T., Li, X-K., Umezawa, A., Kiyono, T
    • Journal Title

      Mol.Biol.Cell 16(3)

      Pages: 1491-1499

    • Related Report
      2004 Annual Research Report
  • [Publications] Imabayashi, H: "Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis."Experimental Cell Research. 288. 35-50 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsushita, K.: "Islet cell hyperplasia in transgenic mice overexpressing EAT/mcl-1, a bcl-2 related gene."Mol Cell Endocr.. 203. 105-116 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sharov, A.A.: "Transcriptome analysis of mouse stem cells and early embryos"PLoS Biology. 1. 410-419 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Gojo, S: "In vivo Cardiovasculogenesis by Direct Injection of Isolated Adult Mesenchymal Stem Cells."Experimental Cell Research. 288. 51-59 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Elizabeth H.Allan: "Differentiation potential of a Mouse bone marrow stromal cell line."Journal of cellular biochemistry. 90. 158-169 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohyama, M.: "Immunologic and histopathologic characterization of active disease model mouse for pemphigus vulgaris"J. Invest. Dermatol.. 118. 199-204 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hakuno, D.: "Bone marrow-derived regenerated cardiomyocytes (CMG cells) express functional adrenergic and muscarinic receptors"Circulation. 105. 380-386 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yabe, H.: "Matrix Metalloproteinase (MMP)-1 and -3 expression in Ewing's sarcoma may be due to loss of accessibility of the MMP regulatory element to the specific fusion protein in vivo"Biochem. Biophys. Res. Commun.. 293. 61-71 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogawa, S.: "A case of dilated cardiomyopathy with end-stage heart failure treated by prolonged continuous hemodiafiltration"Keio. J. Med.. 51・3. 165-177 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki, S.: "Expression of interleukin-6 in cerebral neurons and ovarian cancer tissue in Trousseau syndrome"Clin. Neuropathol.. 21・5. 232-235 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shibata, R: "Correlation between a specific Wilms tumor suppressor gene (Wt1) mutation and the histological findings in Wilms tumor (WT)"J. Med. Genet.. 39・12. E83 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ochi, K.: "The 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.. 194. 45-53 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukuma, M.: "Up-regulation of Id2,an oncogenic helix-loop-helix protein, is mediated by the chimeric EWS/ets protein in Ewing sarcoma"Oncogene. 22. 1-9 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shibata, R.: "Responsiveness of chemotherapy based on the histological type and WT1 mutation in bilateral Wilms tumor"Pathology international. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shibata, R.: "Primary carcinosarcoma of the vagina"Pathology Int.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 五條 理志: "多能性体性幹細胞としての間葉系幹細胞"最新医学. 57・1. 38-46 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 五條 理志: "間葉系幹細胞の分化制御機構"炎症と免疫. 10・1. 13-18 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 梅澤 明弘: "間葉系幹細胞による臓器再生"化学と生物. 40・6. 362-369 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 梅澤 明弘: "間葉系幹細胞(mesenchymaal stem cell)による造血再生"血液・腫瘍科. 44・2. 126-136 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 梅澤 明弘: "間葉系幹細胞"医学のあゆみ. 200・13. 1127-1228 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 梅澤 明弘: "間葉系幹細胞"ゲノム医学. 2・1. 87-94 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 梅澤 明弘: "間葉系幹細胞をもちいた再生医療研究"分子細胞治療. 1・1. 31-37 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 梅澤 明弘: "幹細胞とエピジェネティクス"Molecular Medicine 別刷. 39・7. 816-822 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 梅澤 明弘: "再生医療"小児科臨床. 55・5. 844-846 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 梅沢 明弘: "間葉系幹細胞"再生医学再生医療 現代化学増刊. 41. 16-23 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 梅澤 明弘: "骨芽細胞から神経への転換"最新医学 別刷. 57・7. 1640-1647 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 竹田 征治: "筋ジストロフィーに対する再生治療"医学のあゆみ. 204・3. 179-182 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 梅澤 明弘: "組織幹細胞と生殖細胞の再生医学"ドクターズマガジン. 8・33. 40-41 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 森 泰昌: "再生医学と幹細胞-成体幹細胞"日医雑誌. 129・3. 307-312 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 井出 利憲: "老化研究が分かる"羊土社. 124 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 堀内 正嗣: "生活習慣と遺伝子疾患"メディカルレビュー社. 396 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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