Original Article Transplantation of autologous bone marrow-derived mesenchymal stem cells under arthroscopic surgery with microfracture versus microfracture alone for articular cartilage lesions in the knee: A multicenter prospective randomized control clinical trial Yusuke Hashimoto a , Yohei Nishida a , Shinji Takahashi a , Hiroaki Nakamura a , Hisashi Mera b , Kaori Kashiwa c , Shinichi Yoshiya c , Yusuke Inagaki d , Kota Uematsu d , Yasuhito Tanaka d , Shigeki Asada e , Masao Akagi e , Kanji Fukuda f , Yoshiya Hosokawa g , Akira Myoui g , Naosuke Kamei h , Masakazu Ishikawa h , Nobuo Adachi h , Mitsuo Ochi h , Shigeyuki Wakitani i, * a Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan b Department of Orthopaedic Surgery, Uonuma Kikan Hospital, Minamiuonuma, Japan c Department of Orthopaedic Surgery, Hyogo College of Medicine, Hyogo, Japan d Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan e Department of Orthopaedic Surgery, Kindai University Faculty Medicine, Osaka, Japan f Institute of Advanced Clinical Medicine, Division of Cell Biology for Regenerative Medicine, Faculty of Medicine, Kindai University, Osaka, Japan g Medical Center for Translational Research, Osaka University Hospital, Osaka, Japan h Department of Orthopaedic Surgery, Graduate School of Biomedical & Health Sciences. Hiroshima University, Hiroshima, Japan i Department of Orthopaedic Surgery, Koryokai Hospital, Osaka, Japan article info Article history: Received 6 May 2019 Accepted 6 June 2019 Keywords: Bone marrow-derived mesenchymal stem cells Microfracture Prospective randomized control clinical trial abstract Introduction: To investigate the efficacy of the transplantation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) under arthroscopy with microfracture (MFX) compared with micro- fracture alone. Methods: Eleven patients with a symptomatic articular cartilage defect of the knee were included in the study. They were randomized to receive BMSCs with MFX (cell-T group, n¼7) or MFX alone (control group, n¼4). Clinical results were evaluated using International Knee Documentation committee (IKDC) knee evaluation questionnaires and the Knee Injury and Osteoarthritis Outcome Score (KOOS) before and 48 weeks after surgery. Quantitative and qualitative assessments of repair tissue were carried out at 48 weeks by T2 mapping of magnetic resonance images (MRIs) and the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system with follow-up MRI. Results: No significant differences between preoperative and postoperative IKDC and KOOS were observed in the cell-T or control group. However, forty-eight weeks after surgery, the cell-T group showed a trend for a greater KOOS QOL score compared with the control group (79.4 vs. 39.1, respec- tively; P¼0.07). The T2 value did not differ significantly between the two groups, but the mean MOCART score was significantly higher in the cell-T group than in the control group (P¼0.02). Abbreviations: BMSCs, bone marrow-derived mesenchymal stem cells; MFX, microfracture; IKDC, International Knee Documentation committee; KOOS, Knee Injury and Osteoarthritis Outcome Score; MRIs, magnetic resonance images; MOCART, magnetic resonance observation of cartilage repair tissue; QOL, quality of life; HA, hyaluronic acid; KL, KellgreneLawrence; RCT, randomized controlled trial; CPC, cell processing centers; GFP, green fluorescent protein. * Corresponding author. E-mail addresses: hussy@med.osaka-cu.ac.jp (Y. Hashimoto), haru_the_49ers@ yahoo.co.jp (Y. Nishida), a99m042@yahoo.co.jp (S. Takahashi), hnakamura@med. osaka-cu.ac.jp (H. Nakamura), hisme0214@gmail.com (H. Mera), kaok48@yahoo. co.jp (K. Kashiwa), yoshiya0307@gmail.com (S. Yoshiya), yinagaki@naramed-u.ac. jp (Y. Inagaki), k-uematsu@nara-jadecom.jp (K. Uematsu), yatanaka@naramed-u. ac.jp (Y. Tanaka), asada@med.kindai.ac.jp (S. Asada), makagi@med.kindai.ac.jp (M. Akagi), fukuda@med.kindai.ac.jp (K. Fukuda), yoshiyahosokawa@endmet.med. osaka-u.ac.jp (Y. Hosokawa), myoi@hp-mctr.med.osaka-u.ac.jp (A. Myoui), nahkamei@hiroshima-u.ac.jp (N. Kamei), mishikawa@hiroshima-u.ac.jp (M. Ishikawa), nadachi@hiroshima-u.ac.jp (N. Adachi), ochim@hiroshima-u.ac.jp (M. Ochi), swakitani44@gmail.com (S. Wakitani). Peer review under responsibility of the Japanese Society for Regenerative Medicine. Contents lists available at ScienceDirect Regenerative Therapy journal homepage: http://www.elsevier.com/locate/reth https://doi.org/10.1016/j.reth.2019.06.002 2352-3204/© 2019, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Regenerative Therapy 11 (2019) 106e113