Establishment of salivary gland stem cell isolation, culture, and storage for the regeneration of salivary gland

• Project/Area Number: 22390381
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Matsumoto Dental University (2011-2012); The University of Tokyo (2010)
• Principal Investigator: KAGAMI Hideaki 松本歯科大学, 歯学部, 教授 (80242866)
• Co-Investigator(Kenkyū-buntansha): SUMITA Yoshinori 長崎大学, 医歯薬総合研究科, 准教授 (50456654) ; RI Kenki 松本歯科大学, 総合歯科医学研究所, 講師 (60350831)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2010: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 口腔外科学一般 / 唾液腺 / 再生 / 細胞培養 / 組織工学 / 遺伝子解析 / DNAマイクロアレイ / ディファレンシャルディスプレイ

Research Abstract

The final goal of this study is to develop a novel treatment for salivary gland dysfunction by cell transplantation. First, we established a mouse salivary gland atrophy model by irradiation. The administration of MNCs significantly increased saliva secretion as similar to the experiments with cultured salivary epithelial cells or mesenchymal stem cells. To understand the mechanism of salivary gland recovery by cell transplantation, in vitro salivary gland atrophy model was established. The results from this study have shown that the transplanted cells may affect the function of salary gland acinar cells via factors secreted from MNCs.

Research Products

• [Journal Article] Morphology-based prediction of osteogenic differentiation potential of human mesenchymal stem cells (2013)
  • Author(s): Matsuoka F et al.
  • Journal Title: Plos One Volume: 8 Issue: 2 Pages: e55082-e55082
  • DOI: 10.1371/journal.pone.0055082
  • Peer Reviewed
• [Journal Article] An aberrant parotid gland duct with a cutaneous orifice, accompanied by sialolithiasis. (2013)
  • Author(s): Miyashita M et al.
  • Journal Title: J Oral Maxillofac Surg. Volume: 71 Issue: 1 Pages: 77-82
  • DOI: 10.1016/j.joms.2012.04.007
  • Peer Reviewed
• [Journal Article] Ischemic culture of dental pulp-derived cells is a useful model in which to investigate mechanisms of post-ischemic tissue recovery. (2013)
  • Author(s): Agata H al.
  • Journal Title: Histol Histopathol Volume: 6
  • Peer Reviewed
• [Journal Article] Ischemic culture of dental pulp-derived cells is a useful model in which to investigate mechanisms of post-ischemic tissue recovery. (2013)
  • Author(s): Agata A et al.
  • Journal Title: Histol Histopathol Volume: 6
  • Peer Reviewed
• [Journal Article] Characteristic difference in the composition of osteogenic cell populations of BMSCs isolated from untreated, hemolysed, or Ficoll-treated rat bone marrow (2012)
  • Author(s): Agata H, Yamazaki M, Uehara M, Hori A, Sumita Y, Tojo A, Kagami H
  • Journal Title: Cytotherapy Volume: vol.14(7) Issue: 7 Pages: 791-801
  • DOI: 10.3109/14653249.2012.674639
  • Peer Reviewed
• [Journal Article] Effect of GDF-5 and BMP-2 on the expression of tendo/ligamentogenesis-related markers in human PDL-derived cells (2012)
  • Author(s): Inoue M
  • Journal Title: Oral disease Volume: 18 Issue: 2 Pages: 206-212
  • DOI: 10.1111/j.1601-0825.2011.01871.x
  • Peer Reviewed
• [Journal Article] their similarities and differences revealed from gene expression analyses. (2011)
  • Author(s): Ebisawa K, Kato R, Sugimura T, LatifMA, Hori Y, Narita Y, Ueda M, Honda H, Kagami H. Gingival and dermal fibroblasts
  • Journal Title: J Bioscien Bioeng Volume: 111 Issue: 3 Pages: 255-258
  • DOI: 10.1016/j.jbiosc.2010.11.014
  • Peer Reviewed
• [Journal Article] Bone marrow stromal cells bonemarrow-derived multipotent mesenchymal stromal cells for alveolar bone tissue engineering: basic science to clinical translation. (2011)
  • Author(s): Kagami H., Agata H, Tojo A.
  • Journal Title: Int J. Biochem. Cell Biol. Volume: 43 Issue: 3 Pages: 286-289
  • DOI: 10.1016/j.biocel.2010.12.006
  • Peer Reviewed
• [Journal Article] Bone Marrow Derived Cells : a potential approach for the treatment of xerostomia (2011)
  • Author(s): Tran SD, Sumita Y, Khalili S
  • Journal Title: Int J Biochem Cell Biol Volume: vol.43(1) Issue: 1 Pages: 5-9
  • DOI: 10.1016/j.biocel.2010.10.010
  • Peer Reviewed
• [Journal Article] Microchimerism in salivary glands after blood- and marrow-derived stem cell transplantation (2011)
  • Author(s): Tran SD, Redman RS, Barrett AJ, Pavletic SZ, Key S, Liu Y, Carpenter A, Nguyen HM, Sumita Y, Baum BJ, Pillemer SR, Mezey E
  • Journal Title: Biol Blood Marrow Transplant Volume: vol.17(3) Issue: 3 Pages: 429-433
  • DOI: 10.1016/j.bbmt.2010.09.021
  • Peer Reviewed
• [Journal Article] Bone marrow-derived cells rescue salivary gland function in mice with head and neck irradiation (2011)
  • Author(s): Sumita Y, Liu Y, Khalili S, Maria OM, Xia D, Key S, Cotrim AP, Mezey E, Tran SD
  • Journal Title: Int J Biochem Cell Biol Volume: vol.43(1) Issue: 1 Pages: 80-87
  • DOI: 10.1016/j.biocel.2010.09.023
  • Peer Reviewed
• [Journal Article] A compact, automated cell culture system for clinical scale cell expansion from primary tissues. (2010)
  • Author(s): Kato R, Iejima D, Agata H, Asahina I, Okada K, Ueda M, Honda H, Kagami H
  • Journal Title: Tissue Eng Part C Methods Volume: 16 Issue: 5 Pages: 947-956
  • DOI: 10.1089/ten.tec.2009.0305
  • Peer Reviewed
• [Journal Article] Differential effect of scaffold shape on dentin regeneration (2010)
  • Author(s): Tonomura A, Mizuno D, Hisada A, Kuno N, Ando Y, Sumita Y, Honda MJ, Satomura K, Sakurai H, Ueda M, Kagami H
  • Journal Title: Ann Biomed Eng Volume: vol.38 Issue: 4 Pages: 1664-1671
  • DOI: 10.1007/s10439-010-9910-z
  • Peer Reviewed
• [Journal Article] Efficacy of membranous cultured periosteum for the treatment of patients with severe periodontitis : A proof-of-concept study. (2010)
  • Author(s): Mizuno H, Kagami H, Mase J, Mizuno D, Ueda M.
  • Journal Title: Nagoya J Med Sci Volume: 72 Pages: 59-70
  • NAID: 110007507311
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/20229704.
  • Peer Reviewed
• [Journal Article] Effects of extracellular matrix on differentiation of human bone marrow-derived mesenchymal stem cells into smooth muscle cell lineageUtility for cardiovascular tissue engineering. (2010)
  • Author(s): Suzuki S, Narita Y, Yamawaki A, Murase Y, Satake M, Mutsuga M, Okamoto H, Kagami H, Ueda M, Ueda Y.
  • Journal Title: Cells Tissues Organs Volume: 269-280 Issue: 4 Pages: 269-280
  • DOI: 10.1159/000260061
  • Peer Reviewed
• [Journal Article] Evaluation of scaffold materials fortooth tissue engineering. (2010)
  • Author(s): Ohara T, Itaya T, Usami K, Ando Y, Sakurai H, Honda MJ, Ueda M, Kagami H
  • Journal Title: J Biomed MaterRes A Volume: 94 Issue: 3 Pages: 800-805
  • DOI: 10.1002/jbm.a.32749
  • Peer Reviewed
• [Journal Article] Differential effects of growth/ differentiation factor-5 on the porcine dental papilla- and follicle-derived cells (2010)
  • Author(s): Sumita Y, Kagami H, Honda MJ, Ueda M.
  • Journal Title: Growth Factors Volume: vol.28 Issue: 1 Pages: 56-65
  • DOI: 10.3109/08977190903373380
  • Peer Reviewed
• [Journal Article] Characteristic change and loss of in vivo osteogenic abilities of human bone marrow stromal cells during passage. (2010)
  • Author(s): Agata H, Asahina I, Watanabe N, Ishii Y, Kubo N, Ohshima S, Yamazaki M, Tojo A, Kagami H
  • Journal Title: Tissue. Engineering Part A Volume: 16 Issue: 2 Pages: 663-673
  • DOI: 10.1089/ten.tea.2009.0500
  • Peer Reviewed
• [Journal Article] Limited but heterogeneous osteogenic response of human bone marrow mesenchymal stem cells to bone morphogenetic protein-2 and serum. (2010)
  • Author(s): Mizuno M, Agata H, Furue H, Kimura A, Narita Y, Watanabe N, Ishii Y, Ueda M, Tojo A, Kagami H
  • Journal Title: Growth Factors Volume: 28 Issue: 1 Pages: 34-43
  • DOI: 10.3109/08977190903326362
  • Peer Reviewed
• [Journal Article] Recovery process of sciatic nerve defect with novel bioabsorbable collagen tubes packed with collagen filaments in dogs. (2010)
  • Author(s): Okamoto H, Hata K-I, Kagami H, Okada K, Ito Y, Narita Y, Hirata H, Sekiya I, Otsuka T, Ueda M
  • Journal Title: J Biomed MaterRes A Volume: 92 Issue: 3 Pages: 859-868
  • DOI: 10.1002/jbm.a.32421
  • Peer Reviewed
• [Journal Article] The potential of somatic stem cells for alveolar bone tissue engineering. (2010)
  • Author(s): Kagami H, Agata H.
  • Journal Title: Int. J. Oral-Medical Sci. Volume: 9 Pages: 1-10
  • NAID: 130000411500
  • URL: https://mol.medicalonline.jp/archive/search?jo=de1ijoms&vo=9&nu=1.
  • Peer Reviewed
• [Journal Article] Bone marrow cells are a source of undifferentiated cells to prevent Sjogren's syndrome and to preserve salivary glands function in the non-obese diabetic mice (2010)
  • Author(s): Khalili S, Liu Y, Sumita Y, Maria OM, Blank D, Key S, Mezey E, Tran SD
  • Journal Title: Int J Biochem Cell Biol Volume: vol.42(11) Issue: 11 Pages: 1893-1899
  • DOI: 10.1016/j.biocel.2010.08.008
  • Peer Reviewed
• [Journal Article] The potential of somatic stem cells for alveolar bone tissue engineering. (2010)
  • Author(s): Kagami H, Agata H.
  • Journal Title: Int.J.Oral-Medical Sci Volume: 9 Pages: 1-10
  • NAID: 130000411500
  • Peer Reviewed
• [Journal Article] Efficacy of membranous cultured periosteum for the treatment of patients with severe neriodontitis : A nroof-of-concept study. (2010)
  • Author(s): Mizuno H, Kagami H, et al.
  • Journal Title: Nagoya J Med Sci Volume: 72 Pages: 59-70
  • Peer Reviewed
• [Journal Article] Effects of extracellular matrix on differentiation of human bone marrow-derived mesenchymal stem cells into smooth muscle cell lineage : Utility for cardiovascular tissue engineering. (2010)
  • Author(s): Suzuki S, Narita Y, et al.
  • Journal Title: Cells Tissues Organs Volume: 191 Pages: 269-280
  • Peer Reviewed
• [Journal Article] Evaluation of scaffold materials for tooth tissue engineering. (2010)
  • Author(s): Ohara T, Itaya T, et al.
  • Journal Title: J Biomed Mater Res A Volume: 94 Pages: 800-805
  • Peer Reviewed
• [Journal Article] Morphology-based prediction of osteogenic differentiation potential of human mesenchymal stem cells.
  • Author(s): Matsuoka F, Takeuchi I, Agata H, Kagami H, Shiono H, Kiyota Y, Honda H, Kato R.
  • Journal Title: Plos One
  • Peer Reviewed
• [Journal Article] Ischemic culture of dental pulp-derived cells is a useful model in which to investigate mechanisms of post-ischemic tissue recovery.
  • Author(s): Agata A, Sumita Y, Asahina I, Tojo A, Kagami H
  • Journal Title: Histol Histopathol
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/23629696.
  • Peer Reviewed
• [Presentation] In vitro 唾液腺萎縮モデルによる 唾液腺再生メカニズムの検討 (2013)
  • Author(s): 堀暁子、縣秀樹、上嶋 伸知、東條有伸、 各務 秀明
  • Organizer: 第12回日本再生医療学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-21
• [Presentation] 朝比奈泉歯槽骨・唾液腺の再生研究今後の展開 (2013)
  • Author(s): 各務秀明 、縣秀樹、 住田吉慶
  • Organizer: 第12回日本再生医療学会総会 シンポジウム 5歯科における再生医療の将 来
  • Place of Presentation: 横浜
• [Presentation] 放射線性唾液腺萎縮の in vitro モデルによる検討 (2012)
  • Author(s): 堀暁子、縣秀樹、山崎 美香 、上嶋 伸知、東條有伸、各務秀明
  • Organizer: 第11回日本再 生医療学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-12
• [Presentation] 再生医療における品質管理の 課題:歯槽骨再生治療について 日本臨床試験研究会 (2012)
  • Author(s): 各務秀明
  • Organizer: 第3回学術集会総会 分科会:再生医療 再生医療と規制
  • Place of Presentation: 福岡国際会議場 第1会場 501室
  • Year and Date: 2012-02-24
• [Presentation] 骨髄細胞を用いた骨再生と インプラント治療バイオインテグレーショ ン学会 (2012)
  • Author(s): 各務秀明
  • Organizer: 第2回学術大会・総会
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2012-01-29
• [Presentation] 骨再生医療の現状と展望について (2012)
  • Author(s): 各務秀明
  • Organizer: 第57回日本口腔外科学会総会・学術大会 シンポジウムI 歯・歯周組織・骨の再生医療
  • Place of Presentation: 横浜
• [Presentation] 歯からはじまるアンチエイ ジングーインプラントと骨の再生医療ー (2011)
  • Author(s): 各務秀明
  • Organizer: 第12回 市民公開医療懇談会
  • Place of Presentation: 東京大学医科学研究所附属病院
  • Year and Date: 2011-07-28
• [Presentation] 自己骨髄由来培養骨芽細胞様 細胞による歯槽骨再生 スーパー特区:医 工連携による先進医療機器の実用化プロジェクト (2011)
  • Author(s): 各務秀明
  • Organizer: 第三回シンポジウム文部科学省橋渡し研究支援推進プログラム:先端医療 の開発支援拠点形成と実践第五回シンポジウム
  • Place of Presentation: 東京大学医学部附属病院
  • Year and Date: 2011-02-28
• [Presentation] Bone marrow stromal cells bone marrow-derived multipotent mesenchymal stromal cells for alveolar bone tissue engineering basic science to clinical translation. Thursday, February 28,2013 (2011)
  • Author(s): Kagami H.
  • Organizer: The 16th US-Japan Cellular and Gene Therapy Conference, N
  • Place of Presentation: IDCR, NIH
• [Presentation] Bone marrow stromal cells bone marrow-derived multipotent mesenchymal stromal cells for alveolarbone tissue engineering basic science to clinical translation. (2011)
  • Author(s): Kagami H.
  • Organizer: The Second Chinese National Conference on Oral Maxillofacial Development and Regeneration July 28-31
  • Place of Presentation: Wuyishan city, Fujian Province, China.
• [Presentation] 実用化を目指した新たな歯槽骨再生臨床研究の開始について 第10回松本ボーンフォーラム (2011)
  • Author(s): 各務秀明
  • Organizer: 松本歯科大学 30周年記念棟
  • Place of Presentation: 松本歯科大学 30 周年記念棟
• [Presentation] 自己骨髄由来培養骨芽細胞 様細胞による歯槽骨再生スーパー特区:医 工連携による先進医療機器の実用化プロジ ェクト (2010)
  • Author(s): 各務秀明
  • Organizer: 第三回シンポジウム文部科学省 橋渡し研究支援推進プログラム:先端医療 の開発支援拠点形成と実践第五回シンポジ ウム
  • Place of Presentation: 東京大学医学部附属病院
  • Year and Date: 2010-12-28
• [Presentation] ヒト幹細胞指針に基づいた臨床研究とネットワーク構築によるトランス レーショナルリサーチの展開 (2010)
  • Author(s): 各務秀明
  • Organizer: 日本再生歯科医学会 シンポジウム 自己骨髄間質細胞を用いた歯槽骨再生治療
  • Place of Presentation: 鶴見大学会館 メインホール
  • Year and Date: 2010-12-11
• [Presentation] Bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for alveolar bone tissue engineering: basic science to clinical translation.
  • Author(s): Kagami H
  • Organizer: The 16th US-Japan Cellular and Gene Therapy Conference
  • Place of Presentation: NIH, Bethesda, USA
  • Invited
• [Presentation] 歯槽骨・唾液腺の再生研究今後の展開
  • Author(s): 各務秀明他
  • Organizer: 第12回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Invited
• [Presentation] 骨再生医療の現状と展望について
  • Author(s): 各務秀明
  • Organizer: 第57回日本口腔外科学会総会・学術大会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Invited
• [Presentation] In vitro 唾液腺萎縮モデルによる唾液腺再生メカニズムの検討
  • Author(s): 堀 暁子他
  • Organizer: 第12回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜、横浜市
• [Presentation] 放射線性唾液腺萎縮のin vitroモデルに関する検討
  • Author(s): 堀 暁子他
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜、横浜市
• [Presentation] Bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for alveolar bone tissue engineering: basic science to clinical translation.
  • Author(s): Kagami H
  • Organizer: The 16th US-Japan Cellular and Gene Therapy Conference
  • Place of Presentation: NIH, Bethesda, MD, USA
  • Invited
• [Presentation] Bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for alveolar bone tissue engineering: basic science to clinical translation
  • Author(s): Kagami H
  • Organizer: The Second Chinese National Conference on Oral Maxillofacial Development and Regeneration
  • Place of Presentation: Wuyishan city, Fujian Province, China
  • Invited
• [Presentation] 自己骨髄由来培養骨芽細胞様細胞による歯槽骨
  • Author(s): 各務秀明
  • Organizer: 再生スーパー特区：「医工連携による先進医療機器の実用化プロジェクト」第三回シンポジウム、＊文部科学省 橋渡し研究支援推進プログラム：「先端医療の開発支援拠点形成と実践」第五回シンポジウム
  • Place of Presentation: 東京大学、東京都
  • Invited
• [Presentation] 再生医療における品質管理の課題：歯槽骨再生治療について
  • Author(s): 各務秀明
  • Organizer: 日本臨床試験研究会第３回学術集会総会
  • Place of Presentation: 福岡国際会議場、福岡市
  • Invited
• [Presentation] 骨髄細胞を用いた骨再生とインプラント治療
  • Author(s): 各務秀明
  • Organizer: バイオインテグレーション学会第2回学術大会・総会
  • Place of Presentation: 東京医科歯科大学、東京都
  • Invited
• [Presentation] 実用化を目指した新たな歯槽骨再生臨床研究の開始について
  • Author(s): 各務秀明
  • Organizer: 第10回松本ボーンフォーラム
  • Place of Presentation: 松本歯科大学、塩尻市、長野県
• [Book] TherapeuticApplications in Disease and Injury, Volume2, Springer (2011)
  • Author(s): Kagami H, Agata H, Sumita Y, Tojo A. Heterogeneous responses of human bone marrow stromal cells multipotent mesenchyme stromal cells to osteogenic induction.
  • Publisher: Ed. Hayat MA, Stem Cells and Cancer Stem Cells
• [Book] Fundamental technological developments required for increased availability of tissue engineering. (2011)
  • Author(s): Kagami H, Agata H, Kato R, Matsuoka F, Tojo A.
  • Publisher: Ed. Regenerative Medicine and Tissue Engineering: From Cells to Organs. Intech20113.Kagami H, Agata H, Satake M, Narita Y. Considerations on designing scaffold for soft and hard tissue engineering. Ed. Gilson Khang. The Handbook of Intelligent Scaffold for Regenerative Medicine Pan Stanford Publishing
• [Book] The Handbook of Intelligent Scaffold for Regenerative Medicine Pan Stanford Publishing (2011)
  • Author(s): Kagami H, Agata H, Satake M, Narita Y.
  • Publisher: Considerations on designing scaffold for soft and hard tissue engineering. Ed. Gilson Khang.
• [Book] Stem Cells and Cancer Stem Cells: Therapeutic Applications in Disease and Injury (2011)
  • Author(s): Kagami H et al.
  • Total Pages: 425
  • Publisher: Springer
• [Book] Regenerative Medicine and Tissue Engineering: From Cells to Organs (2011)
  • Author(s): Kagami H et al.
  • Total Pages: 588
  • Publisher: Intech
• [Book] The Handbook of Intelligent Scaffold for Regenerative Medicine (2011)
  • Author(s): Kagami H et al.
  • Total Pages: 974
  • Publisher: Pan Stanford Publishing
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/hematology/terg/index.html