Evaluation of the Usefulness of Human Adipose-Derived Stem Cell Spheroids Formed Using SphereRing<sup>®</sup> and the Lethal Damage Sensitivity to Synovial Fluid In Vitro
Atsushi Fuku,
Yasuhiko Taki,
Yuka Nakamura,
Hironori Kitajima,
Takashi Takaki,
Terutsugu Koya,
Ikuhiro Tanida,
Kaori Nozaki,
Hiroshi Sunami,
Hiroaki Hirata,
Yoshiyuki Tachi,
Togen Masauji,
Naoki Yamamoto,
Yasuhito Ishigaki,
Shigetaka Shimodaira,
Yusuke Shimizu,
Toru Ichiseki,
Ayumi Kaneuji,
Satoshi Osawa,
Norio Kawahara
Affiliations
Atsushi Fuku
Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
Yasuhiko Taki
Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
Yuka Nakamura
Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
Hironori Kitajima
Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
Takashi Takaki
Division of Electron Microscopy, Showa University, Tokyo 142-8555, Japan
Terutsugu Koya
Center for Regenerative Medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan
Ikuhiro Tanida
Genome Biotechnology Laboratory, Kanazawa Institute of Technology, Hakusan 924-0838, Ishikawa, Japan
Kaori Nozaki
Department of Pharmacy, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan
Hiroshi Sunami
Advanced Medical Research Center, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nakagami 903-0215, Okinawa, Japan
Hiroaki Hirata
Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
Yoshiyuki Tachi
Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
Togen Masauji
Department of Pharmacy, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan
Naoki Yamamoto
Center for Clinical Trial and Research Support, Research Promotion and Support Headquarters, Fujita Health University, Toyoake 470-1192, Aichi, Japan
Yasuhito Ishigaki
Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
Shigetaka Shimodaira
Center for Regenerative Medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan
Yusuke Shimizu
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Nakagami 903-0215, Okinawa, Japan
Toru Ichiseki
Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
Ayumi Kaneuji
Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
Satoshi Osawa
Genome Biotechnology Laboratory, Kanazawa Institute of Technology, Hakusan 924-0838, Ishikawa, Japan
Norio Kawahara
Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
Osteoarthritis (OA) is an irreversible degenerative condition causing bone deformation in the joints and articular cartilage degeneration with chronic pain and impaired movement. Adipose-derived stem cell (ADSC) or crushed adipose tissue injection into the joint cavity reportedly improve knee function and symptoms, including pain. Stem cell spheroids may be promising treatment options due to their anti-inflammatory and enhanced tissue regeneration/repair effects. Herein, to form human ADSC spheroids, we used first SphereRing® (Fukoku Co., Ltd., Ageo, Japan), a newly developed rotating donut-shaped tube and determined their characteristics by DNA microarray of mRNA analysis. The variable gene expression cluster was then identified and validated by RT-PCR. Gene expression fluctuations were observed, such as COL15A1 and ANGPTL2, related to vascular endothelial cells and angiogenesis, and TNC, involved in tissue formation. In addition, multiplex cytokine analysis in the medium revealed significant cytokines and growth factors production increase of IL-6, IL-10, etc. However, ADSC administration into the joint cavity involves their contact with the synovial fluid (SF). Therefore, we examined how SF collected from OA patient joint cavities affect 2D-culture ADSCs and ADSC spheroids and observed SF induced cell death. ADSC spheroids could become promising OA treatment options, although studying the administration methods and consider their interaction with SF is essential.
