当科骨軟部腫瘍チームでは、主に下記のような基礎研究、臨床研究を行っております。
骨軟部肉腫における化学療法は発達してきていますが、進行性肉腫における効果は未だ完全ではありません。近年、他の癌においてPD-1/PD-L1免疫チェックポイント機構の関与が示され、PD-1/PD-L1阻害薬が治療に用いられています。当科では肉腫とPD-1/PD-L1免疫チェックポイント機構の関係について病理組織学を中心に研究を行っております。
臨床研究として、炎症と肉腫予後における関係性を調査しております。
炎症が肉腫に与える影響を、主に血液検査データを用いて研究しております。
高齢者(65歳以上)肉腫における治療成績や最善の治療法、また、AYA世代(15-39歳)の問題点、治療法について臨床像を明らかにし、各世代の問題点およびその対策について研究をおこなっております。
この他、JMOG(日本骨軟部腫瘍研究会)に所属し、共同研究に多数参加しています。
私たちは、間葉系幹細胞移植した人工神経鞘の開発を目指し、そのために2014年度より続けて文部科学省科学研究費も獲得し、京都大学整形外科学教室池口良輔准教授と共同して研究しています。ラット坐骨神経欠損モデルで、今まで10mmが限界とされていた神経再生距離を20mmにまで伸ばし、神経再生数、再生軸索直径も自家神経移植の70-80%を達成しました。
(Tanaka H et al. Pros one 2021)
Aoyama T, Goto K, Kakinoki R, Ikeguchi R, Ueda M, Kasai Y, Maekawa T, Tada H, Teramukai S, Nakamura T, Toguchida J.An Exploratory Clinical Trial for Idiopathic Osteonecrosis of Femoral Head by Cultured Autologous Multipotent Mesenchymal Stromal Cells Augmented with Vascularized Bone Grafts. Tissue Eng Part B Rev. 2014 Apr 9. [Epub ahead of print]
Duncan SF, Briski DC, Steinmann SP, Adams J, Kakinoki R. Unique application of a metacarpophalangeal joint implant as a radial head prosthesis. J Shoulder Elbow Surg. 2014 Oct 16;23(12):e308-e312
Ohta S, Kakinoki R, Noguchi T, Kaizawa Y, Matsuda S. Reconstruction of active elbow flexion in patients with radial ray deficiency: report of two cases. J Shoulder Elbow Surg. 2014 Oct 16;23(12):e313-e317.
Aoyama T, Fujita Y, Madoba K, Nankaku M, Yamada M, Tomita M, Goto K, Ikeguchi R, Kakinoki R, Matsuda S, Nakamura T, Toguchida J. Rehabilitation program after mesenchymal stromal cell transplantation augmented by vascularized bone grafts for idiopathic osteonecrosis of the femoral head: A preliminary study. Arch Phys Med Rehabil. 2014 Oct 31. pii: S0003-9993(14)01210-6.
Duncan SF, Hendawi TK, Sperling J, Kakinoki R, Hartsock L. iPhone and iPad Use in Orthopedic Surgery. Ochsner J. 2015 Spring;15(1):52-7. Review.
Duncan SF, Kakinoki R, Rizzo M, Kang W. Extrusion of a NeuroTube: A Case Report. Ochsner J. 2015 Summer;15(2):191-2.
Kakinoki R, Duncan SF, Ikeguchi R, Ohta S, Nankaku M, Sakai H, Noguchi T, Kaizawa Y, Akagi M. Motor and sensory cortical changes after contralateral cervical seventh nerve root (CC7) transfer in patients with brachial plexus injuries. J Hand Surg-AP 2016 in press.
Aoyama T, Fujita Y, Madoba K, Nankaku M, Yamada M, Tomita M, Goto K, Ikeguchi R, Kakinoki R, Matsuda S, Nakamura T, Toguchida J. Rehabilitation program after mesenchymal stromal cell transplantation augmented by vascularized bone grafts for idiopathic osteonecrosis of the femoral head: a preliminary study. Arch Phys Med Rehabil. 2015 Mar;96(3):532-9.
Hirata H, Tanaka K, Sakai A, Kakinoki R, Ikegami H, Tateishi N. Efficacy and safety of collagenase Clostridium histolyticum injection for Dupuytren's contracture in non-Caucasian Japanese patients (CORD-J Study): the first clinical trial in a non-Caucasian population. J Hand Surg Eur Vol. 2016 Jun 16.
Kakinoki R, Hashimoto K, Tanaka H, Akagi M. Suspension Arthroplasty Combined with Ligament Reconstruction of the Thumb CMC Joint to Salvage Two Failed Arthroplasties: A Case Report. J Orthopaedic Case Reports. 2017; 7(1):50-53.
Kakinoki R, Duncan SFM, Ikeguchi R, Ohta S, Nankaku M, Sakai H, Noguchi T, Kaizawa Y, Akagi M. Motor and Sensory Cortical Changes after Contralateral Cervical Seventh Nerve Root (CC7) Transfer in Patients with Brachial Plexus Injuries. J Hand Surg Asian Pac Vol. 2017 Jun;22(2):138-149.
Ikeguchi R, Aoyama T, Kakinoki R, Ueda M, Kasai Y, Maekawa T, Tada H, Yamamoto M, Matsuda S, Nakamura T, Toguchida J. A clinical trial for Kienböck disease by cultured autologous multipotent mesenchymal stromal cells augmented with vascularized bone grafts: A report of five cases. J Orthop Sci. 2017 Mar 5;22(2).
Duncan SFM, Kakinoki R, Dunbar R. Endoscopic Trigger Finger Release: Surgical Technique. J Hand Surg Asian Pac Vol. 2018 Mar;23(1):158-161.
Matsumoto T, Kakinoki R, Ikeguchi R, Ohta S, Akagi M, Matsuda S. .Vascularized Bone Graft to the Lunate Combined With Temporary Scaphocapitate Fixation for Treatment of Stage III Kienböck Disease: A Report of the Results, a Minimum of 2 Years After Surgery. J Hand Surg Am. 2018 Aug;43(8):773.e1-773.e7.
Ryosuke Kakinoki, Kazuhiro Ohtani, Kazuhiko Hashimoto, Hiroki Tanaka, Ryosuke Ikeguchi, Souichi Ohta, Masao Akagi. Use of Dorsal Skin Islands as Firebreak Grafts to the Palm to Reduce the Recurrence Rate of Dupuytren's Contracture. Techniques in Hand and Upper Extremity Surgery. 2018 Sep;22(3):110-115. doi: 10.1097/BTH.0000000000000204.
Kakinoki R, Ohtani K, Hashimoto K, Tanaka H, Ikeguchi R, Ohta S, Akagi M. Use of Dorsal Skin Islands as Firebreak Grafts to the Palm to Reduce the Recurrence Rate of Dupuytren's Contracture. Tech Hand Up Extrem Surg. 2018 Sep;22(3):110-115. doi:10.1097/BTH.0000000000000204.PMID: 30080740
Iemura S, Kakinoki R, Ohtani K, Hashimoto K, Nakamura F, Tanaka H, Akagi M. Treatment of a patient suffering from posttraumatic painful neuromas formed at the bilateral digital nerves of the left middle finger using two neurovascular island flaps. JPRAS Open. 2018 Oct 26;19:1-5. doi: 10.1016/j.jpra.2018.10.001. eCollection 2019 Mar.PMID: 32158846
Tsumura T, Matsumoto T, Matsushita M, Doi H, Shiode H, Kakinoki R. Correction of Humpback Deformities in Patients With Scaphoid Nonunion Using 1,2-Intercompartmental Supraretinacular Artery Pedicled Vascularized Bone Grafting With a Dorsoradial Approach. J Hand Surg Am. 2020 Feb;45(2):160.e1-160.e8. doi: 10.1016/j.jhsa.2019.06.003. Epub 2019 Jul 23.PMID: 31350100
Otani K, Kakinoki R, Akagi M, Kitano N, Ohue M.Delayed Rupture of All Digital Flexor Tendons Following Volar Locking Plate Fixation for Distal Radius Fracture: A Case Report. J Hand Surg Asian Pac Vol. 2021 Jun;26(2):301-304. doi: 10.1142/S2424835521720127.PMID: 33928843
Kakinoki R, Nishichi H, Ikeguchi R, Ohta S, Ohtani K, Akagi M. Vascularized Bone Graft to the Lunate Combined with Shortening of the Capitate and Radius for Treatment of Advanced Kienbock Disease After a Follow-Up for More Than 10 Years. Journal of Hand Surgery Global Online 2020 2 102e108
Kakinoki R, Ikeguchi R, Ohta S, Nishichi H, Tanaka H, Ohtani K, Akagi M. Comparison Between Capsular and Transossous Suture Techniques for Treatment of Triangular Fibrous Cartilage Complex Injuries with Distal Radio-Ulnar Joint Instability. Acta Scientific Orthopedics 2021 4(1): 31-37
Aoyama T, Goto K, Ikeguchi R, Nankaku M, Madoba K, Nagai-Tanima M, Ito A, Kakinoki R, Nakamura T, Matsuda S, Toguchida J. Effect of a Rehabilitation Program After Mesenchymal Stromal Cell Transplantation for Advanced Osteonecrosis of the Femoral Head: A 10-Year Follow-Up Study. Arch Rehabil Res Clin Transl. 2022 Jan 13;4(1):100179. doi: 10.1016/j.arrct.2022.100179. eCollection 2022 Mar.PMID: 35282152
Yamamoto M, Yasunaga H, Kakinoki R, Tsubokawa N, Morita A, Tanaka K, Sakai A, Kurahashi T, Hirata H; CeCORD J study Group. The CeCORD-J study on collagenase injection versus aponeurectomy for Dupuytren's contracture compared by hand function and cost effectiveness. Sci Rep. 2022 May 31;12(1):9094. doi: 10.1038/s41598-022-12966-z.PMID: 35641603
Tsumura T, Matsumoto T, Ikeguchi R, Kakinoki R. Lateral shotgun approach for proximal interphalangeal joint silicone arthroplasty. J Hand Surg Eur Vol. 2023 Apr 26:17531934231170341. doi: 10.1177/17531934231170341. Online ahead of print.PMID: 37125632
Kaizawa Y, Kakinoki R, Ikeguchi R, Ohta S, Noguchi T, Oda H, Matsuda S. Bridging a 30 mm defect in the canine ulnar nerve using vessel-containing conduits with implantation of bone marrow stromal cells.Microsurgery. 2015 Mar 14.
Noguchi T, Ohta S, Kakinoki R, Ikeguchi R, Kaizawa Y, Oda H, Matsuda S. The neuroprotective effect of erythropoietin on spinal motor neurons after nerve root avulsion injury in rats. Restor Neurol Neurosci. 2015 Aug 19;33(4):461-70.
Kakinoki R, Ikeguchi R, Matsumoto T, Nakayama K, Fujita S, Ohta S, Noguchi T, Kaizawa Y, Oda H, Yurie H, Duncan SFM, Hyon S-H, Tomiyama T, Hashimoto H, Tanaka H, Nishimura S, Akagi M. Peripheral nerve storage and allotranplantation using green tea polyphenol in rats – its possibility for clinical application – Review of our works. Achives Kindai University 2016:41(11); 1-8.
Ikeguchi R, Kakinoki R, Thuji H. Peripheral nerve regeneration through a silicone chamber implanted with negative carbon iron. Possibility to clinical application. Appled Surface Science 2014: 310; 19-23
Ikeguchi R, Kakinoki R, Ohta S, Oda H, Yurie H, Kaizawa Y, Mitsui H, Aoyama T, Toguchida J, Matsuda S. Recipient bone marrow-derived stromal cells prolong graft survival in a rat hind limb allotransplantation model. Microsurgery. 2016 Nov 17.
Kaizawa Y, Kakinoki R, Ikeguchi R, Ohta S, Noguchi T, Takeuchi H, Oda H, Yurie H, Matsuda S.A nerve conduit containing a vascular bundle and implanted with bone marrow stromal cells and decellularized allogenic nerve matrix. Cell Transplant. 2016 Feb 16;26(2):215-228.
Tanaka H, Kakinoki R, Kaizawa Y, Yurie H, Ikeguchi R, Akagi M. Bone marrow-derived mesenchymal stem cells transplanted into a vascularized biodegradable tube containing decellularized allogenic nerve basal laminae promoted peripheral nerve regeneration; can it be an alternative of autologous nerve graft? PLoS One. 2021 Aug 31;16(8):e0254968
Kakinoki R, Kaizawa Y, Tanaka H, Akagi M. Artificial nerve conduits with stem cell transplantation used for bridging a long nerve gap; a review of experimental studies in rats. Journal of Stem Cells Research, Development & Therapy. 2021. 7:068
Kakinoki R, Akagi M. Artificial Nerve Containing Stem Cells, Vascularity and Scaffold; Review of Our Studies. Stem Cell Rev Rep. 2023 Feb;19(2):382-391.
Kakinoki R, Ohtani K, Ohta S, Ikeguchi R, Akagi M, Goto K. Treatment of Complete Brachial Plexus Injuries Using Double Free Muscle Transfer. J Hand Surg Am. 2023 Nov 2:S0363-5023(23)00497-5. doi: 10.1016/j.jhsa.2023.09.005. Online ahead of print.
エラスターゼ(蛋白分解酵素)を気管内に投与することでCOPD(慢性閉塞性肺疾患)モデルマウスを作成し、μCTやリアルタイムPCRによってCOPDの筋・骨への影響について調べたところ、下図のように、定性的にも明らかに、肺気腫モデルでは骨量・骨微細構造が障害されていた。(Matsumura D, et al. PLoS One 2023.)
Tmem119をノックアウトしたマウスを使用し、ドリルでマウス大腿骨に骨欠損を作成し、経時的に骨欠損部の面積や新生骨体積を評価することでTmem119欠損により骨修復が遅延することが判明している。その原因を調べるために、骨修復に関わる骨芽細胞・破骨細胞の数や血管新生などについて、組織切片を各種染色することでの評価も行っている。
文責:松村
脂肪や骨髄からMSCを採取・培養し,それを骨や軟骨,脂肪に分化させたり,静脈投与することで再生機能を果たすのかの研究を行っている.
(Toriumi K, et al. iScience 26, 2023.)
文責:鳥海