Regenerative medicine using dedifferentiated fat cell-derived condition media and exosome

• Project/Area Number: 26293170
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Nihon University
• Principal Investigator: MATSUMOTO Taro 日本大学, 医学部, 教授 (50366580)
• Co-Investigator(Kenkyū-buntansha): 副島 一孝 日本大学, 医学部, 准教授 (00246589) ; 加野 浩一郎 日本大学, 生物資源科学部, 教授 (80271039) ; 風間 智彦 日本大学, 医学部, 助手 (80525668)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 脱分化脂肪細胞 / 細胞治療 / 間葉系幹細胞 / 再生医療 / エクソソーム / 再生医学 / 脂肪細胞

Outline of Final Research Achievements

In the present study, we examined the characteristics and therapeutic potential of dedifferentiated fat (DFAT) cell-derived exosomes. As results, we found that DFAT cell-derived exosomes contained a variety of microRNAs that are thought to play important roles in intercellular communications. The expression profile of microRNAs in DFAT cell-derived exosomes was very similar to that in adipose-derived stem cell (ASC)-derived exosomes. DFAT cell-derived exosomes inhibited proliferation of T lymphocytes and promoted differentiation of naive T cells into regulatory T cells. In addition, DFAT cell-derived exosomes stimulated proliferation of nucleus pulposus cells of intervertebral disc and increased expression of SOX9, a critical transcription factor for chondrogenesis. These results suggest that DFAT cell-derived exosomes have therapeutic potential for T cell-mediated autoimmune disorders and intervertebral disc degeneration.

Research Products

• [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] Comparison of capacities to maintain hematopoietic stem cells among different types of stem cells derived from the placenta and umbilical cord. (2016)
  • Author(s): Nishikawa E, Matsumoto T, Ishige M, Tsuji T, Mugishima H, Takahashi S
  • Journal Title: Regenerative Therapy Volume: 4 Pages: 48-61
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An efficient method to obtain dedifferentiated fat cells. (2016)
  • Author(s): Taniguchi H, Kazama T, Hagikura K, Yamamoto C, Kazama M, Nagaoka Y, Matsumoto T
  • Journal Title: Journal of Visualized Experiments Volume: ー Issue: 113
  • DOI: 10.3791/54177
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The effect of mature adipocyte-derived dedifferentiated fat (DFAT) cells on a dorsal skin flap model. (2016)
  • Author(s): Kahimura T, Soejima K, Asamai T, Kazama T, Matsumoto T, Nakazawa H
  • Journal Title: Journal of Investigative Surgery Volume: 29 Issue: 1 Pages: 6-12
  • DOI: 10.3109/08941939.2015.1035820
  • Peer Reviewed
• [Journal Article] Small buccal fat pad cells have high osteogenic differentiateon 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 Engineering Part C: Methods Volume: 22 Issue: 3 Pages: 250-9
  • DOI: 10.1089/ten.tec.2015.0420
  • Peer Reviewed
• [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: Frontier Physiology Volume: 7 Pages: 50-50
  • DOI: 10.3389/fphys.2016.00050
  • Peer Reviewed / Open Access
• [Journal Article] Influence of donor age and passage number on angiogenic activity in human adipose-derived stem cell-conditioned media. (2015)
  • Author(s): Nakamura T, Kazama T, Nagaoka Y, Inamo Y, Mugishima H, Takahashi S, Matsumoto T
  • Journal Title: Journal of Stem Cell Research and Therapy Volume: 5 Issue: 09 Pages: 1000307-1000307
  • DOI: 10.4172/2157-7633.1000307
  • Peer Reviewed / Open Access / 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
• [Journal Article] Effects of mature adipocyte-derived dedifferentiated fat (DFAT) cells on generation and vascularisation of dermis-like tissue after artificial dermis grafting (2015)
  • Author(s): Asami T, Soejima K, Kashimura T, Kazama T, Matsumoto T, Morioka K, Nakazawa H
  • Journal Title: J Plast Surg Hand Surg Volume: 49 Issue: 4 Pages: 1-5
  • DOI: 10.3109/2000656x.2015.1020315
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Smooth muscle-like tissue constructs with circumferentially oriented cells formed by the cell fiber technology. (2015)
  • Author(s): Hsiao AY, Okitsu T, Onoe H, Kiyosawa M, Teramae H, Iwanaga S, Kazama T, Matsumoto T, Takeuchi S.
  • Journal Title: PLoS ONE Volume: 10(3) Issue: 3 Pages: 1-16
  • DOI: 10.1371/journal.pone.0119010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of mature adipocyte-derived dedifferentiated fat (DFAT) cells on generation and vascularisation of dermis-like tissue after artificial dermis grafting (2015)
  • Author(s): Soejima K, Kashimura T, Asami T, Kazama T, Matsumoto T, Nakazawa H
  • Journal Title: J Plast Surg Hand Surg Volume: 49 Issue: 1 Pages: 25-31
  • DOI: 10.3109/2000656x.2014.920712
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Adipocyte-derived and dedifferentiated fat cells promoting facial nerve regeneration in a rat model. (2014)
  • Author(s): Matsumine H., Takeuchi Y., Sasaki R., Kazama T., Kano K., Matsumoto T., Sakurai H., Miyata M., Yamato M.
  • Journal Title: Plast Reconstr Surg Volume: 134 Issue: 4 Pages: 686-697
  • DOI: 10.1097/prs.0000000000000537
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ヒト吸引脂肪組織からの脱分化脂肪細胞の調製 (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: 2017-03-08
• [Presentation] ヒト脱分化脂肪細胞(hDFAT)由来exosomeの免疫抑制能の検討 (2017)
  • Author(s): 小野賀功, 小沼憲祥, 金澤剛二, 後藤俊平, 橋本真, 越永従道, 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: 2017-03-08
• [Presentation] 脱分化脂肪細胞(DFAT)を用いた血管再生細胞治療 (2017)
  • Author(s): 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
  • Invited
• [Presentation] Dedifferentiated fat cells as a new cell source for therapeutic angiogenesis and regenerative medicine. (2016)
  • Author(s): Matsumoto T
  • Organizer: The 22nd Annual Meeting of Japan Society of Gene and Cell Therapy
  • Place of Presentation: 虎ノ門ヒルズ (東京都, 港区）
  • Year and Date: 2016-07-30
  • Invited
• [Presentation] 脱分化脂肪細胞(DFAT)のTSG-6を介した腎症改善効果 (2016)
  • Author(s): 丸山高史, 福田昇, 阿部雅紀, 上野高浩, 松本太郎, 遠藤守人, 岡田一義, 松本紘一, 相馬正義, 河内裕
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜 (神奈川県, 横浜市)
  • Year and Date: 2016-06-18
• [Presentation] 脱分化脂肪細胞（DFAT）の血管壁細胞分化 (2016)
  • Author(s): 後藤俊平, 小沼憲祥, 小野賀功, 橋本真, 渡邉拓史, 萩倉一博, 越永従道, 松本太郎
  • Organizer: 第37回日本炎症・再生医学会
  • Place of Presentation: 京都市勧業館みやこめっせ(京都府, 京都市）
  • Year and Date: 2016-06-16
• [Presentation] ラット椎間板変性モデルに対する脱分化脂肪細胞(DFAT)移植の効果 (2016)
  • Author(s): 中山渕志, 風間智彦, 加野浩一郎, 徳橋泰明, 松本太郎
  • Organizer: 第45回日本脊椎脊髄病学会学術集会
  • Place of Presentation: 幕張メッセ国際会議場・国際展示場 (千葉県, 千葉市)
  • Year and Date: 2016-04-15
• [Presentation] 受動喫煙ラット椎間板変性モデルにおける脱分化脂肪細胞(DFAT)静脈内投与の治療効果 (2016)
  • Author(s): 宮方啓行, 松本太郎, 風間智彦, 小山公行, 上井浩, 徳橋泰明
  • Organizer: 第45回日本脊椎脊髄病学会学術集会
  • Place of Presentation: 幕張メッセ国際会議場・国際展示場 (千葉県, 千葉市)
  • Year and Date: 2016-04-15
• [Presentation] 脂肪細胞を用いた再生医療 (2015)
  • Author(s): 松本太郎
  • Organizer: 第19回日本内分泌病理学会学術総会
  • Place of Presentation: アバンセ佐賀（佐賀県・佐賀市）
  • Year and Date: 2015-10-25
  • Invited
• [Presentation] 受動喫煙ラット椎間板モデルにおける脱分化脂肪細胞(DFAT)静脈内投与の治療効果 (2015)
  • Author(s): 小山公行, 宮方啓行, 風間智彦, 徳橋泰明, 松本太郎
  • Organizer: 第30回日本整形外科学会基礎学術集会
  • Place of Presentation: 富山国際会議場（富山県・富山市）
  • Year and Date: 2015-10-22
• [Presentation] 脱分化脂肪細胞(DFAT)の全身投与はTSG-6を介して免疫性糸球体腎炎を改善した (2015)
  • Author(s): 丸山高史, 福田昇, 渡辺めぐみ, 上野高浩, 阿部雅紀, 松本太郎, 遠藤守人, 岡田一義, 松本紘一, 相馬正義, 河内裕
  • Organizer: 第38回日本高血圧学会総会
  • Place of Presentation: 愛媛県県民文化会館（愛媛県・松山市）
  • Year and Date: 2015-10-09
• [Presentation] ブタ脱分化脂肪細胞の心筋分化指向性の検討 (2015)
  • Author(s): 遠山一人, 風間智彦, 松本太郎, 加野浩一郎, 平山篤志
  • 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] 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] 脱分化脂肪細胞を用いた再生医療 (2015)
  • Author(s): 松本太郎
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 海峡メッセ下関（山口県、下関市）
  • Year and Date: 2015-05-22
  • Invited
• [Presentation] 脱分化脂肪細胞による再生医療 (2014)
  • Author(s): 松本太郎
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: シーガイアコンベンションセンター(宮崎県、宮崎市）
  • Year and Date: 2014-10-25
  • Invited
• [Presentation] 創傷治癒に対する脱分化脂肪 (DFAT) 細胞の効果 (2014)
  • Author(s): 副島一孝, 樫村勉, 山本改, 浅見崇, 風間智彦, 松本太郎, 今田正人, 仲沢弘明
  • Organizer: 第40回日本熱傷学会総会・学術集会
  • Place of Presentation: ラフレさいたま（埼玉県、さいたま市）
  • Year and Date: 2014-06-05
  • Invited
• [Book] 臨床免疫・アレルギー科 第65巻 第6号 (2016)
  • Author(s): 丸山高史, 松本太郎
  • Total Pages: 6
  • Publisher: 科学評論社
• [Remarks] 脱分化脂肪細胞を細胞源とする再生医療
  • URL: http://www.med.nihon-u.ac.jp/department/saisei/dfat.html
• [Remarks] 脱分化脂肪細胞(DFAT)を細胞源とする再生医療
  • URL: http://www.med.nihon-u.ac.jp/department/saisei/dfat.html