The potentiality of adipose tissue-derived stem cells in hematopoietic stem cell transplantation

Research Project

Project/Area Number	15K09667
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Pediatrics
Research Institution	Nippon Medical School
Principal Investigator	HAYAKAWA JUN 日本医科大学, 医学部, 講師 (10386196)
Co-Investigator(Kenkyū-buntansha)	植田高弘日本医科大学, 医学部, 准教授 (20322505)
Research Collaborator	Uchimura Ryoichi
Project Period (FY)	2015-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000) Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	脂肪幹細胞 / 間葉系幹細胞 / 血管炎 / 抗炎症効果 / 骨髄不全症 / 脂肪由来骨髄間葉系幹細胞 / 造血支持組織 / 脂肪由来間葉系幹細胞 / 造血不全症
Outline of Final Research Achievements	Although Mesenchymal stem cells (MSCs) regulate in immune response and bone marrow recovery, adipose-tissue derived mesenchymal stem cells (ADSCs) are still not well defined. Similar possibility was expected by ADSCs as alternated tool of MSCs. The harvest of ADSCs was less invasive and more safe. We tried to evaluate the behavior of ADSCs in vivo mice model. In vasculitis model, we demonstrated that ADSCs has anti-inflammatory and immune regulatory functions by suppressed cytokines such as IL-1b and TNF-α, IL10, IL-13, IL-17. Our pathological data also suggested ADSCs do not act directly on the site of inflammation, suppressing pro-inflammatory related cytokines causes reduction of vasculitis by acting indirectly through some factors. Further studies required to clarify the role of ADSCs, ADSCs could potentially lead to unique tools in therapeutic strategies of vasculitis and bone marrow recovery.
Academic Significance and Societal Importance of the Research Achievements	安定した脂肪由来間葉系幹細胞(ADSC)を樹立し生態に投与することで生体内での働きを評価した。マウスから樹立した脂肪幹細胞をマウス血管炎モデルに投与したところ、ADSCが造血回復の際に血管炎の抑制に寄与することを示した。ADSCはIL-17やTNF-αといった炎症関連サイトカインを抑制することで冠動脈などの大動脈での炎症の改善に貢献し抗炎症効果をもたらすことを証明できた。しかし、本研究で目標とした骨髄不全症疾患などの造血幹細胞移植時における脂肪幹細胞の有用性の評価と造血回復への関与に関しての充分なdataは得ることができず今後の課題として残された。