Regeneration using adipose-derived stem cells and fluorescent imaging evaluation for a defect after bone and soft tissue tumor surgery

• Project/Area Number: 26462271
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kanazawa University
• Principal Investigator: Hayashi Katsuhiro 金沢大学, 附属病院, 助教 (80507054)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 脂肪由来幹細胞 / 骨軟部腫瘍

Outline of Final Research Achievements

We compared osteogenic and adipogenic differentiation potency between MSCs isolated and cultured from normal adipose tissues and atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) from the same patients. We found greater osteogenic differentiation potency in ALT/WDL-derived MSCs than in normal fat-derived MSCs. In adipogenic differentiation, contrary to our expectations, more fatty acid droplets were observed in normal fatderived MSCs than in ALT/WDL-derived MSCs. In osteogenic differentiation, as expected, MSCs derived from ALT/WDL had higher differentiation potency than normal fat-derived MSCs. The gap of osteogenic differentiation potency based on ALP staining between ALT/WDL-derived MSCs and normal fat-derived MSCs disappeared as Nutlin-3 concentration increased, suggesting that greater osteogenic differentiation could be caused by amplied MDM2 in ALT/WDL.

Research Products

• [Journal Article] Do Mesenchymal Stem Cells Derived From Atypical Lipomatous Tumors Have Greater Differentiation Potency Than Cells From Normal Adipose Tissues? (2017)
  • Author(s): Inatani H, Yamamoto N, Hayashi K, Kimura H, Takeuchi A, Miwa S, Higuchi T, Abe K, Taniguchi Y, Yamada S, Asai K, Otsuka T, Tsuchiya H.
  • Journal Title: Clin Orthop Relat Res Volume: 印刷中 Issue: 6 Pages: 1693-1701
  • DOI: 10.1007/s11999-017-5259-z
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 運動器再生医療における脂肪由来幹細胞の潜在能力 (2016)
  • Author(s): 林克洋
  • Journal Title: 臨床整形外科 Volume: 51 Pages: 635-639
  • NAID: 40020890789
• [Journal Article] The paracrine effect of adipose-derived stem cells inhibits osteoarthritis progression. (2015)
  • Author(s): Kuroda K, Kabata T, Hayashi K, Maeda T, Kajino Y, Iwai S, Fujita K, Hasegawa K, Inoue D, Sugimoto N, Tsuchiya H.
  • Journal Title: BMC Musculoskelet Disord. Volume: 16 Issue: 1
  • DOI: 10.1186/s12891-015-0701-4
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Salvage method for unplanned excision of soft tissue sarcoma: long-term results of second-look surgery following radio-hyperthermo-chemotherapy. (2015)
  • Author(s): Hayashi K, Yamada S, Inatani H, Okamoto H, Takeuchi A, Nishida H, Yamamoto N, Tsuchiya H, Otsuka T
  • Journal Title: Anticancer Res. Volume: 35 Pages: 493-498
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Factors that influence functional outcome after total or subtotal scapulectomy: Japanese Musculoskeletal Oncology Group (JMOG) study. (2014)
  • Author(s): Hayashi K, Iwata S, Ogose A, Kawai A, Ueda T, Otsuka T, Tsuchiya H.
  • Journal Title: PLoS One Volume: 9 Issue: 6 Pages: e100119-e100119
  • DOI: 10.1371/journal.pone.0100119
  • Peer Reviewed / Open Access
• [Journal Article] Uncultured autogenous adipose-derived regenerative cells promote bone formation during distraction osteogenesis in rats. (2014)
  • Author(s): Nomura I, Watanabe K, Matsubara H, Hayashi K, Sugimoto N, Tsuchiya H.
  • Journal Title: Clin Orthop Relat Res Volume: 472 Issue: 12 Pages: 3798-806
  • DOI: 10.1007/s11999-014-3608-8
  • Peer Reviewed
• [Journal Article] A novel method to apply osteogenic potential of adipose derived stem cells in orthopaedic surgery (2014)
  • Author(s): Fang X, Murakami H, Demura S, Hayashi K, Matsubara H, Kato S, Yoshioka K, Inoue K, Ota T, Shinmura K, Tsuchiya H
  • Journal Title: PLoS One Volume: 9(2) Issue: 2 Pages: e88874-e88874
  • DOI: 10.1371/journal.pone.0088874
  • Peer Reviewed / Open Access
• [Presentation] From Fat to Bone: Making Adipose Derived Stem Cell Sheets and Osteogenesis of Adipose Derived Stem Cell Sheets (2017)
  • Author(s): Xiang Fang, Katsuhiro Hayash, Hideki Murakami, Hiroyuki Tsuchiya
  • Organizer: American Academy of Orthopedic Surgeons
  • Place of Presentation: Convention Center (USA)
  • Year and Date: 2017-03-14
  • Int'l Joint Research
• [Presentation] 脂肪腫と異型脂肪腫瘍腫瘍／高分化型脂肪肉腫70例の臨床的特徴の比較 (2016)
  • Author(s): 稲谷弘幸, 山本憲男, 林克洋, 武内章彦, 三輪真嗣, 樋口貴史, 阿部健作, 谷口裕太, 土屋弘行
  • Organizer: 第49回日本整形外科学会骨軟部学術集会
  • Place of Presentation: 東京ドームホテル（東京）
  • Year and Date: 2016-07-14
• [Presentation] The Comparative Analysis Of Differentiation Potency Between The Mesenchymal Stem Cells Derived From The Same Human Normal Adipose Tissue And Atypical Lipomatous Tumor (2016)
  • Author(s): Inatani H, Yamamoto N, Hayashi K, Kimura H, Takeuchi A, Miwa S, Otsuka T, Tsuchiya H
  • Organizer: 11th Asia Pacific Musculoskeletal Tumor Society Meeting
  • Place of Presentation: Grand Copthorne Waterfront (シンガポール）
  • Year and Date: 2016-04-21
  • Int'l Joint Research
• [Presentation] A novel method to apply adipose-derived stem cells to bone and soft tissue defects after tumor excision. (2015)
  • Author(s): Hayashi K
  • Organizer: International Society of Limb Salvage & Musculoskeletal Tumor Society combined meeting
  • Place of Presentation: W Marriott Orlando Grande Lakes (USA)
  • Year and Date: 2015-10-06
  • Int'l Joint Research
• [Presentation] The comparative analysis of differentiation potency between the mesenchymal stem cells derived from the same human normal adipose tissue and atypical lipomatous tumor (2015)
  • Author(s): Inatani H, Yamamoto N, Hayashi K
  • Organizer: International Society of Limb Salvage & Musculoskeletal Tumor Society combined meeting
  • Place of Presentation: W Marriott Orlando Grande Lakes (USA)
  • Year and Date: 2015-10-06
  • Int'l Joint Research
• [Presentation] 骨端を含む悪性骨腫瘍に対して液体窒素処理した自家骨軟骨移植術の経験 (2015)
  • Author(s): 林克洋
  • Organizer: 第125回中部日本整形外科災害外科学会・学術集会
  • Place of Presentation: ウインクあいち (名古屋）
  • Year and Date: 2015-10-02
• [Presentation] Case analysis of poor prognostic bone sarcoma patient who underwent tumor-bearing frozen autograft (2014)
  • Author(s): 林克洋
  • Organizer: 低温医学学会総会
  • Place of Presentation: 野依記念学術交流館（愛知県名古屋市）
  • Year and Date: 2014-11-13 – 2014-11-14
• [Presentation] The diagnosis using MDM2 and CDK4 for low-grade osteosarcoma and treatment with biologic reconstruction (2014)
  • Author(s): Katsuhiro Hayashi
  • Organizer: Societe Internationale de Chirurgie Orthopedique et de Traumatologie
  • Place of Presentation: SulAmerica Convention Centre (Brazil)
  • Year and Date: 2014-11-09 – 2014-11-22
• [Presentation] マウス内で肉腫細胞の転移臓器播種リアルタイムイメージング (2014)
  • Author(s): 林克洋
  • Organizer: 第 23回日本がん転移学会
  • Place of Presentation: 文化ホール（石川県金沢市）
  • Year and Date: 2014-07-10 – 2014-07-11