Dedifferentiated fat (DFAT) cells as a new donor cells for regenerative medicine.

• Project/Area Number: 15H04607
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Integrative animal science
• Research Institution: Nihon University
• Principal Investigator: KANO Koichiro 日本大学, 生物資源科学部, 教授 (80271039)
• Co-Investigator(Kenkyū-buntansha): 沖 嘉尚 日本大学, 生物資源科学部, 助教 (70525667) ; 森友 忠昭 日本大学, 生物資源科学部, 教授 (20239677) ; 伊藤 大介 日本大学, 生物資源科学部, 講師 (40508694) ; 北川 勝人 日本大学, 生物資源科学部, 教授 (50409067)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 成熟脂肪細胞 / 自発的脱分化 / 分化多能性 / 脱分化脂肪細胞 / 獣医再生医学 / 内臓脂肪組織 / 内視鏡 / 脱分化 / 細胞数 / 神経細胞 / 再生医療 / 脱分分化脂肪細胞 / 神経細胞分化誘導 / セロトニン作動性神経細胞 / グルタミン酸作動性神経細胞 / 再生医学 / DFAT細胞 / 多分化能 / 人工多能性細胞 / 細胞移植治療 / 細胞・組織 / 獣医学

Outline of Final Research Achievements

When mature adipocytes are subjected to an in vitro dedifferentiation strategy referred to as ceiling culture, these mature adipocytes can revert to a more primitive phenotype and gain cell proliferative ability. We refer to these cells as dedifferentiated fat (DFAT) cells. In the present study, we examined the multilineage differentiation potential of DFAT cells. DFAT cells obtained from adipose tissues of various animals exhibited a fibroblast-like morphology and sustained high proliferative activity. In vitro differentiation analysis revealed that DFAT cells could differentiate into adipocytes, osteoblasts and nerve cells under appropriate culture conditions. These results indicate that DFAT cells represent a type of multipotent progenitor cell. Since DFAT cells can be prepared from a small quantity of adipose tissue, they could facilitate cell-based therapies in small companion Animals such as dogs and cats.

Research Products

• [Journal Article] Transplantation of dedifferentiated fat cell-derived micromass pellets contributed to cartilage repair in the rat osteochondral defect model. (2018)
  • Author(s): Shimizu Manabu, Matsumoto Taro, Kikuta Shinsuke, Ohtaki Munenori, Kano Koichiro, Taniguchi Hiroaki, Saito Shu, Nagaoka Masahiro, Tokuhashi Yasuaki
  • Journal Title: Journal of Orthopedic Science Volume: 23 Issue: 4 Pages: 688-696
  • DOI: 10.1016/j.jos.2018.03.001
  • Peer Reviewed / Open Access
• [Journal Article] Effect of collagenase concentration on the isolation of small adipocytes from human buccal fat pad (2018)
  • Author(s): Tsurumachi N, Akita D, Kano K, Matsumoto T, Toriumi T Kazama T, Oki Y, Saito-Tamura Y, Tonogi M, Shimizu N, Honda M
  • Journal Title: Journal of Oral Science Volume: 60 Issue: 1 Pages: 14-23
  • DOI: 10.2334/josnusd.16-0786
  • NAID: 130006539176
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access
• [Journal Article] Transplantation of mature adipocyte-derived dedifferentiated fat cells into three-wall defects in the rat periodontium induces tissue regeneration (2017)
  • Author(s): Suzuki D, Akita D, Tsurumachi N, Kano K, Yamanaka K, Kaneko T, Kawano E, Iguchi S, Toriumi T, Arai Y, Matsumoto T, Sato S, Honda M
  • Journal Title: Journal of Oral Science Volume: 59 Issue: 4 Pages: 611-620
  • DOI: 10.2334/josnusd.16-0878
  • NAID: 130006286520
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access
• [Journal Article] Transplantation of dedifferentiation fat cells promotes intervertebral disc regeneration in a rat intervertebral disc degeneration model (2017)
  • Author(s): Nakayama Enshi、Matsumoto Taro、Kazama Tomohiko、Kano Koichiro、Tokuhashi Yasuaki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 493 Issue: 2 Pages: 1004-1009
  • DOI: 10.1016/j.bbrc.2017.09.101
  • Peer Reviewed / Open Access
• [Journal Article] Dedifferentiated fat cells, as a novel source for cell therapy to target neonatal hypoxic ischemic encephalopathy. (2017)
  • Author(s): Mikrogeorgiou A, Kondo T, Hattori T, Sugiyama Y, Nakanishi K, Tsuji M, Kazama T, Kano K, Matsumoto T, Hayakawa M, Sato Y
  • Journal Title: Developmental Neuroscience Volume: 印刷中 Issue: 1-4 Pages: 273-286
  • DOI: 10.1159/000455836
  • Peer Reviewed
• [Journal Article] Transplantation of mature adipocyte-derived dedifferentiated fat cells for treatment of vesicoureteral reflux in a rat model. (2016)
  • Author(s): Ikado Y, Obinata D, Matsumoto T, Murata Y, Kano K, Fukuda N, Yamaguchi K, Takahashi S
  • Journal Title: International Urology and Nephrology Volume: 48 Issue: 12 Pages: 1951-1960
  • DOI: 10.1007/s11255-016-1426-5
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Use of Rat Mature Adipocyte-Derived Dedifferentiated Fat Cells as a Cell Source for Periodontal Tissue Regeneration (2016)
  • Author(s): Akita D, Kano K, Saito-Tamura Y, Mashimo T, Sato-Shionome M, Tsurumachi N, Yamanaka K, Kaneko T, Toriumi T, Arai Y, Tsukimura N, Matsumoto T, Ishigami T, Isokawa K, Honda M.
  • Journal Title: Front Physiol Volume: 7 Pages: 50-50
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Small Buccal Fat Pad Cells Have High Osteogenic Differentiation Potential. (2016)
  • Author(s): Tsurumachi N, Akita D, Kano K, Matsumoto T, Toriumi T, Kazama T, Oki Y, Tamura Y, Tonogi M, Isokawa K, Shimizu N, Honda M
  • Journal Title: Tissue Eng Part C Methods Volume: 22 Pages: 250-259
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increases in TNF-stimulated gene 6 (2015)
  • Author(s): Maruyama T, Fukuda N, Matsumoto T, et al.
  • Journal Title: Stem Cell Research & Therapy Volume: 6 Issue: 1 Pages: 1-16
  • DOI: 10.1186/s13287-015-0069-2
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 成熟脂肪細胞に由来する脱分化脂肪細胞DFATの肝細胞への分化 (2018)
  • Author(s): 萩原玲子, 沖 嘉尚, 加野浩一郎
  • Organizer: 日本畜産学会第124回大会
• [Presentation] 成熟脂肪細胞由来のDFAT細胞はセロトニンおよびグルタミン酸作動性神経細胞へと分化する (2017)
  • Author(s): 沖嘉尚、渡辺真平、松本太郎、加野浩一郎
  • Organizer: 日本畜産学会第122回大会
  • Place of Presentation: 神戸大学（兵庫県神戸市）
  • Year and Date: 2017-03-27
• [Presentation] ヒト吸引脂肪組織からの脱分化脂肪細胞の調整 (2017)
  • Author(s): 風間智彦、山元智衣、風間美奈子、長岡悠紀、谷口浩章、萩倉一博、加野浩一郎、相川佳之、松本太郎
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2017-03-07
• [Presentation] Identification of the master regulator gene for hepatocyte differentiation in de-differentiated fat (DFAT) cells (2017)
  • Author(s): Hagiwara R, Oki Y, Kano K
  • Organizer: 第40回日本分子生物学会年会
• [Presentation] 成熟脂肪細胞から多能性細胞をつくる ~脱分化脂肪細胞DFATの開発とその特性~ (2017)
  • Author(s): 加野浩一郎
  • Organizer: 第86回原爆後障害医療研究所 研究集会
  • Invited
• [Presentation] 成熟脂肪細胞から多能性細胞をつくる ~DFAT細胞の特性と再生医療への応用展開~ (2017)
  • Author(s): 加野浩一郎
  • Organizer: 先端医療実用化推進事業シンポジウム
  • Invited
• [Presentation] イヌ脱分化脂肪細胞のレチノイン酸および塩基性線維芽脂肪成長因子による神経分化 (2017)
  • Author(s): 中野令、加野浩一郎、松本太郎、杉谷博士
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] 成熟脂肪細胞に由来する脱分化脂肪細胞のセロトニン作動性神経細胞様細胞への分化 (2016)
  • Author(s): 渡辺真平、沖 嘉尚、松本太郎、加野浩一郎
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-12-01
• [Presentation] 成熟脂肪細胞に由来する多能性細胞DFATの開発とその特性 ～獣医領域における再生医療への応用～ (2016)
  • Author(s): 加野浩一郎
  • Organizer: 第159回日本獣医学会学術集会
  • Place of Presentation: 日本大学（神奈川県藤沢市）
  • Year and Date: 2016-09-06
  • Invited
• [Presentation] 終末分化した体細胞から多能性細胞をつくる ～自発的な脱分化と多能性獲得～ (2016)
  • Author(s): 加野浩一郎
  • Organizer: 第８回日本創傷外科学会総会・学術集会
  • Place of Presentation: メトロポリタンホテル東京池袋（東京都豊島区）
  • Year and Date: 2016-07-21
  • Invited
• [Presentation] Dedifferentiated fat cells, a novel source for cell therapy to target neonatal hypoxia-ischemia (2016)
  • Author(s): Alkisti Mikrogeorgiou、佐藤義朗、杉山裕一朗、鈴木俊彦、北瀬悠磨、近藤大貴、中西圭子、辻雅弘、風間智彦、松本太郎、加野浩一郎、早川昌弘
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪国際会議（大阪市北区）
  • Year and Date: 2016-03-17
• [Presentation] 吸引脂肪組織を利用した脱分化脂肪細胞DFATの調製と機能評価 (2015)
  • Author(s): 風間智彦，副島一孝，加野浩一郎，松本太郎
  • Organizer: 第36回日本炎症再生医学会
  • Place of Presentation: 虎ノ門ヒルズフォーラム（東京都港区）
  • Year and Date: 2015-07-21
• [Presentation] 脱分化脂肪細胞移植による歯周組織再生の試み (2015)
  • Author(s): 本田雅規，秋田大輔，加野浩一郎，鶴町仁奈，鳥海拓，井口慎也，鈴木大悟，河野英輔，松本太郎，磯川桂太郎
  • Organizer: 第58回春季日本歯周病学会学術大会
  • Place of Presentation: 幕張メッセ 国際会議場（千葉市美浜区）
  • Year and Date: 2015-05-15
• [Presentation] 脱分化脂肪細胞(DFAT)の臨床用細胞製造と細胞治療への応用 (2015)
  • Author(s): 副島一孝, 松本太郎, 樫村勉, 風間智彦, 加野浩一郎, 仲沢弘明
  • Organizer: 第58回日本形成外科学会総会・学術集会
  • Place of Presentation: ウェスティン都ホテル京都（京都市東山区）
  • Year and Date: 2015-04-08
• [Patent(Industrial Property Rights)] 哺乳動物由来の脱分化脂肪細胞から神経細胞を製造する方法及び哺乳動物由来の脱分化脂肪細胞から神経細胞への分化誘導用キット (2017)
  • Inventor(s): 杉谷博士，中野令，松本太郎，加野浩一郎
  • Industrial Property Rights Holder: 学校法人 日本大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-237231
  • Filing Date: 2017