研　究

Research

輸血・細胞移植学

安全かつ適正な輸血医療の推進と造血細胞移植、細胞治療を基礎から臨床まで支援する
宮﨑浩二教授
宮﨑　浩二
Koji
Miyazaki
教授
担当科目輸血学、血液内科学、血管学
専門分野輸血・細胞治療学、臨床血液学、血栓止血学
キーワード輸血、細胞治療、造血細胞移植、血栓止血、血小板、巨核球造血、細胞骨格蛋白質、再生医療、医療安全

スタッフ
北里大学医学部　輸血・細胞移植学
教授：宮﨑　浩二
講師：大谷　慎一
診療講師：大津　真
助教：石田　隆（米国Fred Hutchinson癌研究所に留学中）

教育について
輸血医療は、医療安全上重要な分野です。特に、医師、看護師、検査技師やMEなど他職種におよぶチーム医療の良いモデルでもあります。さらに、造血細胞移植医療は、多くの診療科、栄養部、緩和ケア、患者支援センターなどとの連携が必要なチーム医療の最たるものです。したがって、本単位は、チーム医療の推進や医療安全文化の醸成のために、大きな役割を果たすべき部門と考えます。臨床面では、日本輸血・細胞治療学会認定医、臨床輸血看護師、アフェレーシスナースを育て、安全かつ適正な輸血診療を推進し、再生医療や樹状細胞療法などの研究的先端医療では、基礎研究から前臨床段階（臨床応用）にわたって今後発展が期待される分野ですので、各科各研究室と連携しながら、リサーチマインドをもった医師を育てていきたいと考えています。

研究について
1. 我が国におけるヘモビジランス体制の確立
日本輸血・細胞治療学会において、輸血に伴う全副作用情報をもれなく収集するシステムの構築に向けて、各社の電子カルテに対応可能なものを検討、作成中です。
 
2. 臨床試験
血液内科領域、特に血栓止血領域（血小板減少症、血友病など）、造血細胞移植領域における治験、臨床試験に参画しています。
 
3. 複数ユニットを用いた新規臍帯血移植法の開発、および造血幹細胞の体外増幅法、移植後の生着制御、造血幹細胞の質の劣化の防止、造血幹細胞の機能温存法に関する研究
石田助教、大津診療講師が東大医科研（中内研究室）で行ってきた研究テーマであり、今後も関連した研究を継続して行う予定です。
 
4. 遺伝性血小板減少症の病態生理に関する研究
岐阜医療科学大学、成育医療センターとの共同研究で遺伝性巨大血小板減少症の病態についての研究を行っています。
 
5. 免疫性血小板減少症の病態解明
本学医療衛生学部　佐藤隆司講師との共同研究で、免疫性血小板減少症の病態解明に関する研究を行っています。

大学院生募集
輸血、血栓止血、細胞治療、移植再生医療に関心があり、やる気のある大学院生を募集しています。

国内外の研究室と共同研究を行っています。海外では、テキサス大学　池辺光男教授の研究室にこれまでも本学から留学生をお願いしております。池辺研究室では、細胞骨格タンパク質、特にミオシンスーパーファミリーなどのモータータンパクを中心にその生物学的機能を最新の画像技術や分子生物学的手法を駆使して研究しており、世界のトップジャーナルに成果を掲載し続けています。世界を相手に活躍できるように、やる気のある方は、ぜひチャレンジしてほしいと思います。

主な研究業績
 
  1. Hadland B, Varnum-Finney B, Dozono S, Dignum T, Nourigat-McKay C, Heck AM, Ishida T, Jackson DL, Itkin T, Butler JM, Rafii S, Trapnell C, Bernstein ID.: Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics. Nat Commun. Mar 24;13(1):1584, 2022.
  2. Nakazato T, Hagihara M, Sahara N, Tamai Y, Ishii R, Tamaki S, Wake A, Tajika K, Sakai R, Kobayashi T, Hua J, Inoue M, Aisa Y, Fujisawa S, Miyazaki K, Irie S, Tanaka E, Higashihara M.: Phase II clinical trial of personalized VCD-VTD sequential therapy using the Vulnerable Elders Survey-13 (VES-13) for transplant-ineligible patients with newly diagnosed multiple myeloma. Ann Hematol. 100(11):2745-2754, 2021.
  3. Wada N, Uojima H, Satoh T, Okina S, Iwasaki S, Shao X, Takiguchi H, Arase Y, Itokawa N, Atsukawa M, Miyazaki K, Hidaka H, Kako M, Kagawa T, Iwakiri K, Horie R, Suzuki T, Koizumi W.: Impact of Anti-GPIIb/IIIa antibody-producing B cells as a predictor of the response to lusutrombopag in thrombocytopenic patients with liver disease. Dig Dis. 39(3):234-242, 2021. doi: 10.1159/000510692.
  4. Uchiyama T, Takahashi S, Nakabayashi K, Okamura K, Edasawa K, Yamada M, Watanabe N, Mochizuki E, Yasuda T, Miura A, Kato M, Tomizawa D, Otsu M, Ariga T, Onodera M.: Nonconditioned ADA-SCID gene therapy reveals ADA requirement in the hematopoietic system and clonal dominance of vector-marked clones. Mol Ther Methods Clin Dev. 23:424-433, 2021.
  5. Dignum T, Varnum-Finney B, Srivatsan SR, Dozono S, Waltner O, Heck AM, Ishida T, Nourigat-McKay C, Jackson DL, Rafii S, Trapnell C, Bernstein ID, Hadland B.: Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo. Cell Rep. 36(11):109675, 2021.
  6. Jang JH, Tomiyama Y, Miyazaki K, Nagafuji K, Usuki K, Uoshima N, Fujisaki T, Kosugi H, Matsumura I, Sasaki K, Kizaki M, Sawa M, Hidaka M, Kobayashi N, Ichikawa S, Yonemura Y, Enokitani K, Matsuda A, Ozawa K, Mitani K, Lee JW, Nakao S.: Efficacy and safety of romiplostim in refractory aplastic anemia: a Phase II/III, multicentre, open-label study. Br J Haematol. 192:190-199, 2021.
  7. Paciullo F, Bury L, Noris P, Falcinelli E, Melazzini F, Orsini S, Zaninetti C, Abdul-Kadir R, Obeng-Tuudah D, Heller P, Glembotsky AC, Fabris F, Rivera J, Lozano ML, Butta N, Favier R, Cid AR, Fouassier M, Podda GM, Santoro C, Grandone E, Henskens Y, Nurden P, Zieger B, Cuker A, Devreese K, Tosetto A, De Candia E, Dupuis A, Miyazaki K, Othman M, Gresele P. : Antithrombotic prophylaxis for surgery-associated venous thromboembolism risk in patients with inherited platelet disorders. The SPATA-DVT Study. Haematologica. 105(7):1948-1956, 2020.
  8. Gresele P, Orsini S, Noris P, Falcinelli E, Alessi MC, Bury L, Borhany M, Santoro C, Glembotsky AC, Cid AR, Tosetto A, De Candia E, Fontana P, Guglielmini G, Pecci A; BAT-VAL study investigators.(Heller PG, Rodorigo G, Lammle B, Trinchero A, Paolo R, Ferrari S, Rancitelli D, Stolinski A, Arulselvan A, Lassandro G, Luceros AS, Jandrot-Perrus M, Kunishima S, Rivera Pozo J, Lordkipanidzé M, Melazzini F, Falaise C, Casonato A, Podda G, Kannan M, Jurk K, Sevivas T, Castaman G, Grandone E, Fiore M, Zuniga P, Henskens Y, Miyazaki K, Dupuis A, Hayward C, Zaninetti C, Abid M, Ferrara G, Mazzucconi MG, Tagariello G, James P, Fabris F, Russo A, Bermejo N, Napolitano M, Curnow J, Vasiliki G, Zieger B, Fedor M, Chitlur M, Lambert M, Barcella L, Cosmi B, Giordano P, Porri C, Eker I, Morel-Kopp MC, Deckmyn H, Frelinger AL 3rd, Harrison P, Mezzano D, Mumford AD). :Validation of the ISTH/SSC bleeding assessment tool for inherited platelet disorders: A communication from the Platelet Physiology SSC. J Thromb Haemost. 2020 Mar;18(3):732-739.
  9. Izumida E, Suzawa T, Miyamoto Y, Yamada A, Otsu M, Saito T, Yamaguchi T, Nishimura K, Ohtaka M, Nakanishi M, Yoshimura K, Sasa K, Takimoto R, Uyama R, Shirota T, Maki K, Kamijo R. Functional Analysis of PTH1R Variants Found in Primary Failure of Eruption. J Dent Res. 2020;99(4):429-36.
  10. Yokohama A, Okuyama Y, Ueda Y, Itoh M, Fujiwara SI, Hasegawa Y, Nagai K, Arakawa K, Miyazaki K, Makita M, Watanabe M, Ikeda K, Tanaka A, Fujino K, Matsumoto M, Makino S, Kino S, Takeshita A, Muroi K.: Differences among hemoglobin thresholds for red blood cell transfusions in patients with hematological diseases in teaching hospitals: a real world data in Japan. Int J Hematol. 112:535-543, 2020.
  11. Horigome Y, Tadera N, Michishita Y, Motohashi T, Ishida T, Okina S, Kamata H, Miyazaki K, Suzuki T.: Acute leukemia developing in the second trimester of pregnancy. Rinsho Ketsueki. 61(8):865-869, 2020.
  12. Heck A, Ishida T, Hadland B : Location, location, location: How vascular specialization influences hematopoietic fates during development. Front Cell Dev Biol. 8:602617, 2020.
  13. Okumura T, Horie Y, Lai CY, Lin HT, Shoda H, Natsumoto B, Fujio K, Kumaki E, Okano T, Ono S, Tanita K, Morio T, Kanegane H, Hasegawa H, Mizoguchi F, Kawahata K, Kohsaka H, Moritake H, Nunoi H, Waki H, Tamaru SI, Sasako T, Yamauchi T, Kadowaki T, Tanaka H, Kitanaka S, Nishimura K, Ohtaka M, Nakanishi M, Otsu M. Robust and highly efficient hiPSC generation from patient non-mobilized peripheral blood-derived CD34(+) cells using the auto-erasable Sendai virus vector. Stem Cell Res Ther. 2019;10(1):185.
  14. Yamamoto T, Otsu M, Okumura T, Horie Y, Ueno Y, Taniguchi H, Ohtaka M, Nakanishi M, Abe Y, Murase T, Umehara T, Ikematsu K. Generation of three induced pluripotent stem cell lines from postmortem tissue derived following sudden death of a young patient with STXBP1 mutation. Stem Cell Res. 2019;39:101485.
  15. Kawata M, Mori D, Kanke K, Hojo H, Ohba S, Chung UI, Yano F, Masaki H, Otsu M, Nakauchi H, Tanaka S, Saito T. Simple and Robust Differentiation of Human Pluripotent Stem Cells toward Chondrocytes by Two Small-Molecule Compounds. Stem Cell Reports. 2019;13(3):530-44.
  16. Ishida T, Miyazaki K, Okina S, Miyata T, Hayama K, Higashihara M, Suzuki T.: The clinical outcomes of chronic myeloid leukemia patients harboring alternatively spliced BCR-ABL variants. Hematology 24(1):49-51, 2019.
  17. Ishida T, Ohashi K, Okina C, Ohashi S, Okina S, Miyazaki K, Suzuki T.: Characteristics of palliative home care for patients with hematological tumors compared to those of patients with solid tumors. Int J Hematol.  Aug;110(2):237-243, 2019. (DOI: 10.1007/s12185-019-02673-3).
  18. Sakai R, Ohmachi K, Sano F, Watanabe R, Takahashi H, Takasaki H, Tanaka M, Hattori Y, Kimura H, Takimoto M, Tachibana T, Tanaka E, Ishii Y, Ishiyama Y, Hagihara M, Miyazaki K, Yamamoto K, Tomita N, Ando K. :Bendamustine-120 plus rituximab therapy for relapsed or refractory follicular lymphoma: a multicenter phase II study. Ann Hematol. 2019 Sep;98(9):2131-2138, 2019.
  19. Ikebe E, Matsuoka S, Tanaka A, Yonemura Y, Fujii Y, Ohsaka A, Okazaki H, Kitazawa J, Ohtani S, Nakayama T, Momose SY, Miwa I, Taira R, Toyota K, Kino S, Kato H, Hamaguchi I.: Reduction in adverse transfusion reactions with increased use of washed platelet concentrates in Japan-A retrospective multicenter study. Transfus Apher Sci. 58(2):162-168, 2019.
  20. Uojima H, Arase Y, Itokawa N, Atsukawa M, Satoh T, Miyazaki K, Hidaka H, Sung JH, Kako M, Tsuruya K, Kagawa T, Iwakiri K, Horie R, Koizumi W.: Relationship between response to lusutrombopag and splenic volume. World J Gastroenterol. 24(46): 5271-5279, 2018.
  21. Ishida T, Akagawa N, Miyata T, Tominaga N, Iizuka T, Higashihara M, Suzuki T, Miyazaki K. Dasatinib-associated reversible demyelinating peripheral polyneuropathy in a case of chronic myeloid leukemia. Int J Hematol. 107(3):373-377, 2018.
  22. Tsukune Y, Sasaki M, Odajima T, Sunami K, Takei T, Moriuchi Y, Iino M, Isoda A, Nakaya A, Muta T, Miyake T, Miyazaki K, Shimizu T, Nakajima K, Igarashi A, Nagafuji K, Kurihara T, Aoyama T, Sugimori H, Komatsu N. Incidence and risk factors of hepatitis B virus reactivation in patients with multiple myeloma in an era with novel agents: a nationwide retrospective study in Japan. Blood Cancer J. 7:e631, 2017.
  23. Kamata H, Miyazaki K, Komatsu S, Jung HS, Craig R, Higashihara M, Suzuki T, Ikebe M.: Mutation in the tail region of MYH9 inhibits disassembly of nonmuscle myosin IIA. Kitasato Med. J. 47: 31-42, 2017.
  24. Ishida T, Yokoyama M, Danbara M, Michishita Y, Horie R, Higashihara M, Miyazaki K.: Successful treatment with ibrutinib of intractable thrombocytopenia associated with recurrent chronic lymphocytic leukemia. Kitasato Med. J. 47: 81-86, 2017.
  25. Orsini S, Noris P, Bury L, Heller PG, Santoro C, Kadir RA, Butta NC, Falcinelli E, Cid AR, Fabris F, Fouassier M, Miyazaki K, Lozano ML, Zuñiga P, Flaujac C, Podda GM, Bermejo N, Favier R, Henskens Y, De Maistre E, De Candia E, Mumford AD, Ozdemir NG, Eker I, Nurden P, Bayart S, Lambert MP, Bussel J, Zieger B, Tosetto A, Melazzini F, Glembotsky AC, Pecci A, Cattaneo M, Schlegel N, Gresele P. Bleeding risk of surgery and its prevention in patients with inherited platelet disorders. The Surgery in Platelet disorders And Therapeutic Approach (SPATA) study. Haematologica. 102(7):1192-1203, 2017.
  26. Ishida T, Suzuki S, Lai C Y, Yamazaki S, Kakuta S, Iwakura Y, Nojima M, Takeuchi Y, Higashihara M, Nakauchi H, Otsu M. Pre-Transplantation Blockade of TNF-alpha-Mediated Oxygen Species Accumulation Protects Hematopoietic Stem Cells. Stem Cells 35(4):989-1002, 2017.
  27. Yokoyama M, Ichinoe M, Okina S, Sakurai Y, Nakada N, Yanagisawa N, Jiang S X, Numata Y, Umezawa A, Miyazaki K, Higashihara M, Murakumo, Y. CD109, a negative regulator of TGF-beta signaling, is a putative risk marker in diffuse large B-cell lymphoma. Int J Hematol. 105(5):614-622, 2017.
  28. Aoyama N, Nishinari M, Ohtani S, Kanai A, Noda C, Hirata M, Miyamoto A, Watanabe M, Minamino T, Izumi T, Ako J.：Clinical features and predictors of patients with critical limb ischemia who responded to autologous mononuclear cell transplantation for therapeutic angiogenesis. Heart Vessels. 32(9):1099-1108, 2017.
  29. Ishida T, Takahashi S, Lai C Y, Nojima M, Yamamoto R, Takeuchi E, Takeuchi Y, Higashihara M, Nakauchi H, Otsu M. Multiple allogeneic progenitors in combination function as a unit to support early transient hematopoiesis in transplantation. J Exp Med. 213(9):1865-80, 2016.
  30. Miyazaki K, Koike Y, Kunishima S, Ishii R, Danbara M, Horie R, Yatomi Y, Higashihara M. Immature platelet fraction measurement is influenced by platelet size and is a useful parameter for discrimination of macrothrombocytopenia. Hematology. 20(10):587-592, 2015.
  31. Takeuchi Y, Takeuchi E, Ishida T, Onodera M, Nakauchi H, Otsu M. Curative haploidentical BMT in a murine model of X-linked chronic granulomatous disease. Int J Hematol. 102:111-120, 2015.
  32. Ishida T, Yamazaki S, Nakauchi H, Higashihara M, Otsu M. Reactive oxygen species in hematopoietic stem cells affect culture outcomes under inflammatory conditions. Open Journal of Hematology 6-7, 2015.
  33. Nakajima Y, Hattori Y, Ito S, Ohshima R, Kuwabara H, Machida S, Shirasugi Y, Miyazaki K, Sakai R, Tomita N, Ando K, Higashihara M, Ishigatsubo Y, Fujisawa S.: Acute leukemia during pregnancy: an investigative survey of the past 11 years. Int J Lab Hematol. 37(2):174-80, 2015.
  34. Satoh T, Miyazaki K, Shimohira A, Amano N, Okazaki Y, Nishimoto T, Akahoshi T, Munekata S, Kanoh Y, Ikeda Y, Higashihara M, Takahashi S, Kuwana M. Fcγ receptor IIB gene polymorphism in adult Japanese patients with primary immune thrombocytopenia. Blood. 122(11):1991-2, 2013.
  35. Kunishima S, Okuno Y, Yoshida K, Shiraishi Y, Sanada M, Muramatsu H, Chiba K, Tanaka H, Miyazaki K, Sakai M, Ohtake M, Kobayashi R, Iguchi A, Niimi G, Otsu M, Takahashi Y, Miyano S, Saito H, Kojima S, Ogawa S.  ACTN1 Mutations Cause Congenital Macrothrombocytopenia. Am J Hum Genet. 92(3): 431-438, 2013.
  36. Makita S, Aoki T, Watarai A, Aida A, Katayama T, Danbara M, Higashihara M, Miyazaki K. Acquired hemophilia associated with autoimmune bullous diseases: a report of two cases and a review of the literature. Inter. Med. 52(7): 807-810, 2013.
  37. Danbara, M., Tadera, N., Togano, T., Katayama, T., Aoki, T., Miyazaki, K., Higashihara, M.: Lenalidomide-induced acute lung injury in case of multiple myeloma. Int. J. Clin. Pharmacol. Ther. 51(6): 513-516, 2013.
  38. Suzuki Y, Yoshida T, Wang G, Aoki T, Katayama T, Miyamoto S, Miyazaki K, Iwabuchi K, Danbara M, Nakayama M, Horie R, Nakamine H, Sato Y, Nakamura N, Niitsu N.: Incidence and Clinical Significance of Aberrant T-Cell Marker Expression on Diffuse Large B-Cell Lymphoma Cells. Acta Haematol. 130(4): 230-237, 2013.
  39. Aoki T, Miyazaki K, Katayama T, Watanabe M, Horie R, Danbara M, Higashihara M. Surface CD3 expression proceeds through both myosin regulatory light chain 9 (MYL9)-dependent and MYL9-independent pathways in Jurkat cells. J. Smooth Muscle Res. 48(5,6): 137-147, 2012.
  40. Shirasugi Y, Ando K, Miyazaki K, Tomiyama Y, Iwato K, Okamoto S, Kurokawa M, Kirito K, Hashino S, Ninomiya H, Mori S, Yonemura Y, Usuki K, Wei H, Lizambri R. : An open-label extension study evaluating the safety and efficacy of romiplostim for up to 3.5 years in thrombocytopenic Japanese patients with immune thrombocytopenic purpura (ITP). Int J Hematol. 95(6):652-9, 2012.
  41. Miyazaki, K., Kamata, H., Kimura, H., Okina, S., Ishii, R., Ohsaka, M., Danbara, M., Horie, R., Higashihara, M. : The efficacy and safety of piperacillin-tazobactam for febrile neutropenic patients in Japan. Rinsho Ketsueki 53(7): 686-690, 2012.
  42. Numata A, Fujimaki K, Aoshima T, Onizuka M, Hagihara M, Miyazaki K, Fujita H, Sakai R, Machida S, Tanaka E, Nakajima Y, Hattori Y, Tanaka M, Yamazaki E, Shirasugi Y, Inoue Y, Watanabe S, Fujisawa S. : Retrospective analysis of treatment outcomes in 70 patients with t(8;21) acute myeloid leukemia. Rinsho Ketsueki 53(7):698-704, 2012.
  43. Suzuki Y, Yoshida T, Wang G, Togano T, Miyamoto S, Miyazaki K, Iwabuchi K, Nakayama M, Horie R, Niitsu N, Sato Y, Nakamura N: Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL. Ann Hematol. 91(7):997-1005, 2012.
  44. Nihonyanagi S, Kanoh Y, Okada K, Uozumi T, Kazuyama Y, Yamaguchi T, Nakazaki N, Sakurai K, Hirata Y, Munekata S, Ohtani S, Takemoto T, Bandoh Y, Akahoshi T.：Clinical usefulness of multiplex PCR lateral flow in MRSA detection: a novel, rapid genetic testing method. Inflammation. 35(3):927-34, 2012.
  45. Shirasugi Y, Ando K, Miyazaki K, Tomiyama Y, Okamoto S, Kurokawa M, Kirito K, Yonemura Y, Mori S, Usuki K, Iwato K, Hashino S, Wei H, Lizambri R. : Romiplostim for the treatment of chronic immune thrombocytopenia in adult Japanese patients: a double-blind, randomized Phase III clinical trial. Int J Hematol. 94(1):71-80, 2011.
 
 

お問い合わせ
北里大学医学部　輸血・細胞移植学
〒252-0374　神奈川県相模原市南区北里1-15-1
E-mail： miyazakk@med.kitasato-u.ac.jp