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1 Toward an Asian MSC Hybrid Banking System Program & Abstracts Meeting President Surapol Issaragrisil Chairperson of Asian Hematology Association (AHA) Kun Soo Lee Chairperson of AsiaCORD Shigetaka Asano Date: May 1-2, 2015 Venue: Sysmex Technopark, Kobe URL :

2 Welcome to KOBE CBTは Adult Tissuesに 比 べたPerinatal Tissuesの 臨 床 利 用 の 優 位 点 を 明 らかにしつつあ ります 今 回 のAsiaCORDとAHAとの 合 同 Meetingでの 議 論 を 通 じて その 科 学 的 解 析 に 関 する 関 心 の 高 まりによって 私 たちにとって 魅 力 ある 活 動 指 針 が 定 まり アジア 国 際 共 同 研 究 が 活 性 化 することを 期 待 します Cord blood transplantation has been clarifying some clinical advantages of perinatal tissues over adult tissues. I expect that our concern on these advantages will rise further, define our action plans and activate an Asian international joint research work through active and fruitful discussion at this Combined Meeting of AsiaCORD and AHA. Surapol Issaragrisil, MD, FRCP, FACP, FRCPA,FRCPath President of AsiaCORD/AHA2015 Professor, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand HSCTにおける 私 たちの 最 大 の 関 心 事 の 一 つが 前 処 置 によって 惹 き 起 こされる 炎 症 免 疫 応 答 異 常 の 個 体 差 であることは 今 も 変 わりがありません その 個 体 差 を 科 学 的 エビデ ンスに 基 づいて 解 明 することの 重 要 性 が 本 Meeting において 再 認 識 されるようになれば HSCT の 成 績 の 更 なる 向 上 のみならず 諸 種 疾 患 の 発 症 の 予 測 予 防 法 のための 議 論 が 活 発 化 することになると 確 信 しています One of our major concerns in clinical hematopoietic stem cell transplantation (HSCT) still remains an individual difference in tissue damages by abnormal inflammatory-immune reactions induced mainly by the conditioning regimen and post-transplant use of immune suppressive agents. More thrusting discussions on scientific analysis of the individual differences at this Meeting will lead not only further improvement of HSCT but also development of the perspective and preventive methods of various kinds of disease. Kun Soo Lee, M.D., Ph.D. Chairperson of Asian Hematology Association-AHA Professor, Kyungpook National University School of Medicine, Korea 炎 症 免 疫 反 応 を 担 うMSCsとそのProgeniesのDynamicsに 焦 点 を 当 てた 研 究 は Stratified Medicineあるいは4P- 保 健 医 療 の 道 を 開 くことになります その 最 も 重 要 な 基 盤 となる Hybrid MSC Bankがアジア 各 国 で 構 築 されれば それらの 連 携 による 国 際 比 較 研 究 と 人 材 交 流 が 大 きく 進 展 するでしょう 本 Meetingでそれに 向 けた 前 向 きの 具 体 的 計 画 が 纏 まる ことを 期 待 しています The research focusing on dynamism of mesenchymal stem cells and their progenies, which function in inflammatory and immune process will open a way toward stratified medicine. Hybrid MSC Banking System established in each country of Asia will stimulate international cooperative research and young researcher/clinician exchange. I hope to discuss on feasible plans to establish this system at this Meeting. Shigetaka Asano, M.D., D.M.Sci. Chairperson of AsiaCORD Professor Emeritus, The University of Tokyo, and Waseda University 1

3 AsiaCORD/AHA2015 in KOBE Members of the Committee Meeting President: Surapol Issaragrisil Chairperson of Asian Hematology Association(AHA): Kun Soo Lee Chairperson of AsiaCORD: Shigetaka Asano Organizing Committee Surapol Issaragrisil, Nguyen Tan Binh, Shang-Hsien Yang, Kaiyan Liu, Pakpoom Kheolamai, Sun Hee Kim, Mari Dezawa, Sonoko Habu, Tokiko Nagamura, Keiya Ozawa, Yuzuru Kanakura, Hiromi Kumon, Tsuneo Takahashi, Yong Mook Choi, Kun Soo Lee, Shigetaka Asano AsiaCORD Past Meetings History of AsiaCORD (Since 2000 ~ 2013) Meeting s name Date Site President Founding meeting of AsiaCORD1999 November 9, 2000 Bangkok Prof. Surapol Issaragrisil AsiaCORD2001 June 23, 2001 Tokyo Prof. Shigetaka Asano AsiaCORD2002 June 28-29, 2002 Tokyo Prof. Shigetaka Asano AsiaCORD2003 October 10-11, 2003 Tokyo Prof. Shigetaka Asano AsiaCORD2011 July 2, 2011 Beijing Prof. Kai-Yan Liu AsiaCORD2013 April 19-20, 2013 Kobe Prof. Shigetaka Asano Asian Hematology Association-AHA Past Meetings History of AHA (Since 2003 ~ 2012) Meeting s name Date Site President 1 st General Assembly of AHA 2003 March 1-2, 2003 Kobe Prof. Shigetaka Asano 2 nd General Assembly of AHA 2004 June 25-27, 2004 Beijing Prof. Daopei Lu 3 rd General Assembly of AHA 2005 August 17-20, 2005 Jeju Prof. Kun Soo Lee 4 th General Assembly of AHA 2007 February 24-25, 2007 Bangkok Prof. Surapol Issaragrisil 5 th General Assembly of AHA 2009 February 13-14, 2009 Kobe Prof. Shigetaka Asano Kick off Meeting of AHA 2012 August 4, 2012 Kobe Prof. Shigetaka Asano Kobe Main Office: (Headquarters) NPO Strategic Network for Consolidated Research of Medical Sciences in Asia (SN-CRMSA) Kobe Biotechnology Research and Human Resource Development Center : Kobe University Business Incubation Center 2F: (BT center) 1-5-6, Minami-cho, Minatoshima, Chuo-ku, Kobe, Hyogo, , Japan or 2

4 Meeting Location General Information All of the AsiaCORD/ AHA 2015 Scientific Sessions will take place at the Sysmex Technopark. Address: Takatsukadai, Nishi-ku, Kobe , Japan. On-Site Registration Registration Fees entitle each participant to one copy of the final program including the abstracts for the meeting and admission to all scientific sessions. Registration open hours: May 1 (Fri) : 11:00am - 17:00pm May 2 (Sat) : 8:00am - 17:00pm Registration Fee: Regular JPY 5,000, free for student with verification card. GENERAL INFORMATION Method of Payment: Japanese Yen (JPY), Cash Only! Payment will only be acceptable at the Registration Desk during the Meeting. All payments must be made in Japanese Yen. No other currencies are acceptable. Registration Fees entitle the participants to: All Scientific Sessions, Program & Abstract Book. Welcome Reception On Friday evening, May 1, you are invited to a Welcome Reception at the cafeteria inside Sysmex Technopark (Technocafe). The reception will start from 18:30pm to 20:30pm. The fee will be JPY2,000. If you wish to join, please purchase tickets at the registration desk during open hours. Light meal and drinks will be served and anyone is welcome to join, so please take this opportunity to network and interact with your colleagues. For more information, please contact our staffs at the registration desk. Instruction for Speakers 1. The language for oral presentation and slides should be in English. No simultaneous interpretation will be provided. 2. All Sessions will be held at the Main Hall. 3. All speakers are requested to bring their presentation data in a CD-ROM or USB Flash Memory drive which should be formatted to run on Windows-based PC. OS and application software for presentation data are Windows 7 or later and PowerPoint 2007 or later. 4. The font should be basic (Arial, Times New Roman, etc.) to avoid display problems. 5. For Macintosh users, please bring your laptop computer at your own risk since it will not be supported by the computers at the venue. 6. Macintosh users are required to bring an AC adapter and a VGA adapter (D-Sub15). 3

5 GENERAL INFORMATION & FLOOR MAP PC Station 1. Speakers on Day 1 are requested to bring their presentation data in a CD-ROM or USB Flash Memory to the PC Station next to Registration Desk at least 1 hour before your presentation is scheduled. Speakers on Day 2 are requested to bring their presentation data on Day 1, May 1 (Fri). 2. For Macintosh users, please ask for further instructions from the AV technicians at the PC Station. 3. Please place all video clips linked with the PowerPoint presentation into a single folder. Video file should be WMV or MPEG1, not MPEG2. 4. Presentation data loaded on the computer will be completely deleted after your presentation by our staffs. Floor Map Techno Café Open Hours Day 1 : 15:20-16:30 Day 2 : 09:00-14:30, 15:00-16:00 No ordering at the Café Coffee on Day 1 & 2 and lunch on Day 2 will be provided for free Vending Machines for drinks are allowed Prohibited Area (Do not enter upstairs) To Techno Cafe Techno Café Room 2 SN-CRMSA Office Room 1 Business Meeting Stage Main Hall Registration Desk PC Station Rest Room Entrance to Hall ATTENTION: No Smoking, Eating or Drinking outside designated areas. 4

6 Map of Sysmex Technopark Map of Venue VENUE Turn right at this traffic light after you take the right road at the 3 way junctio n. Route to Registration Desk Please follow the yellow route if you are using a bus or taxi to the venue on DAY 1 & 2 Please follow the blue route if you are walking from the station to the venue on DAY 1 Please follow the brown route if you are walking from the station to the venue on DAY 2 RESTRICTED AREA RESTRICTED AREA Restricted Areas are Red Shaded Areas Central Office Techno Café (outside designated times) 2nd floor above of the Main Hall Building (except for the route from the waiting area to the registration desk on Day 1 ) From the Waiting Area, please go upstairs and walk through the corridor above the café to the registration desk. Smoking area Please enter through the East Entrance if you are using a bus or a taxi. Central Office East Entrance RESTRICTED AREA Techno Cafe PC Station Please enter through the Main Entrance if you are walking from the station. Main Entrance Registration Desk RESTRICTED AREA 5

7 ACCESS INFORMATION Access Information Route from Airports to the Hotel and Venue From Kansai International Airport (http://www.kansai-airport.or.jp/en/index.asp) Limousine Bus to Sannomiya Station (aprox. 75 min., One-way fare: JPY 1,950,) Round-trip fare: JPY 3,080) From Itami Airport (http://osaka-airport.co.jp/en/) (Sannomiya Station is a few minutes walk from the bus terminal) Limousine Bus to Sannomiya Station (aprox. 40 min., Fare: JPY 1,050) Shin-Kobe Station Kobe City Subway Sannomiya Station Shin-Kobe Station is 1 stop from Sannomiya Station aprox. 3 min., Fare: JPY th stop from Seishin-chuo Station aprox. 33 min., Fare: JPY 400 Kobe City Subway From Sannomiya to Seishin-chuo (aprox. 30 min., Fare: JPY 400) ANA CROWNE PLAZA KOBE Located in front of Shin-Kobe Station. (Please use the joint connecting passage to the Hotel) 4 Floor : Hotel Front B3 Floor : Kobe City Subway Shin-Kobe Station (14 th stop from Sannomiya Station) Seishin-chuo Station KOBE SEISHIN ORIENTAL HOTEL (Located in front of Seishin-chuo Station) 8 min. on foot to the venue Venue: Sysmex Technopark Address: Takatsukadai, Nishi-ku, Kobe Tel: (+81)

8 Access Map Access Information Map to Sysmex Technopark from Seishin-chuo Station Our Staff will be positioned to guide the way ( ) Please receive Exchange Ticket from our staff at the entrance gates. Staff 3 way junction Technopark East Gate Entrance for people by vehicle Main Gate Entrance for people on foot from the station ACCESS INFORMATION East Exit <Route from Seishin-chuo Station to Sysmex Technopark> Sogoundokoen Myodan i Myohoji Shin-Kobe Station Please take the Kobe City Subway from here for people staying at ANA CROWNE PLAZA KOBE Sysmex Technopark is 8 min. walk from the East Exit of Seishin-chuo Station. Pass Kobe Seishin Oriental Hotel to your right and walk approx. 500 m. to a 3 way junction. Take the right road to the next traffic light and turn right to the Main Gate. Itayado Shin-Nagata Kenchomae Okurayama Minatogawa koen Kamisawa Nagata 7

9 SCHEDULE AT A GLANCE Friday, May 1, 2015 Schedule-at-a-Glance 11:00-17:00 Registration Open Hours 13:00-13:15 Opening Remarks: Surapol Issaragrisil 13:15-13:30 Welcome Greetings: Hisashi Ietugu (Video Message) Osamu Nagayama (Video Message) 13:30-14:00 Presidential Lecture: Surapol Issaragrisil 14:00-15:20 Session 1-1: Immune Dysfunctions after HSCT :20-15:35 - Coffee Break - 15:35-17:35 Session 1-2: Immune Dysfunctions after HSCT :35-18:30 Tour inside Sysmex Technopark Welcome Reception 18:30-20:30 Welcome Speech: Yoshimi Takai, Hisafumi Okabe, Kaoru Asano, et.al. Saturday, May 2, :00-17:00 Registration Open Hours 08:00-08:45 AsiaCORD/AHA Business Meeting 09:00-12:20 Session 2: Mesenchymal Stem Cell (MSC) Properties 12:20-13:10 - Lunch - 13:10-15:00 Session 3: Future of Stratified Medicine 15:00-15:10 - Coffee Break - 15:10-17:30 Session 4: Round Discussion for Hybrid MSC Bank Network 17:30-17:40 Closing Remarks: Kun-Soo Lee 8

10 Surapol Issaragrisil (Mahidol University) AsiaCORD: History and the Future Day I (May 1, 2015) Presidential Lecture Chairperson: Shigetaka Asano 13:30 ~ 14:00 Session 1-1 Immune Dysfunctions after HSCT (Organized by Chugai Pharmaceutical Co., Ltd.) 14:00 ~ 15:20 Chairpersons: Kun-Soo Lee, Kaiyan Liu, Arinobu Tojo 14:00 ~ 14:40 1. Eun-Suk Kang (Sungkyunkwan University School of Medicine) An Overview of Immune Reconstitution after Hematopoietic Stem Cell Transplantation 14:40 ~ 15:20 2. Yosuke Takahama (The University of Tokushima) T cell formation in thymus microenvironments Session 1-2 Immune Dysfunctions after HSCT (Organized by Chugai Pharmaceutical Co., Ltd.) 15:35 ~ 17:35 Chairs: Eun-Suk Kang, Kaiyan Liu, Tokiko Nagamura DAY I SCIENTIFIC PROGRAM HIGHLIGHTS 15:35 ~ 16:15 3. Satoshi Takahashi (The Institute of Medical Science, The University of Tokyo) Immune reconstitution and dysfunction after HSCT: difference between BMT and CBT 16:15 ~ 16:55 4. Kaiyan Liu (Peking University People s Hospital) The comparative outcomes of unrelated cord blood transplantation with haploidentical hematopoietic stem-cell transplants for pediatric hematologic malignances 16:55 ~ 17:35 5. Cladd E. Stevens (Memorial Sloan Kettering Cancer Center, NY) Immunological Factors Affecting the Outcome of Umbilical Cord Blood (CB) Transplantation 9

11 DAY II SCIENTIFIC PROGRAM HIGHLIGHTS Day II (May 2, 2015) Session 2 Mesenchymal Stem Cell (MSC) Properties (Organized by Sysmex Corporation) 09:00 ~ 12:20 Chairpersons: Tran Van Binh, Shang-Hsien Yang, Yuzuru Kanakura 1. Makoto Asashima (Advanced Industrial Science and Technology (AIST)) Developing Biology of MSCs 2. Mari Dezawa (Tohoku University Graduate School of Medicine) Discovery of Muse cells shift the paradigm of mesenchymal stem cells 09:00 ~ 09:50 09:50 ~ 10:20 10:20 ~ 10:50 3. Zhong-Chao Han (Chinese Academy of Medical Sciences & Peking Union Medical College) Perinatal mesenchymal stem cells: immunomedulation activity and their therapeutic roles in refractory blood diseases 10:50 ~ 11:20 4. Mitsuhiro Itoh (Kobe University Graduate School of Health Sciences) Relationship to Tissue-specific Stem Cells 11:20 ~ 11:50 5. Pakpoom Kheolamai (Thammasat University) The effects of mesenchymal stem cell-derived cytokines on the functional properties of endothelial progenitor cells 11:50 ~ 12:20 6. Keiya Ozawa (The Institute of Medical Science, The University of Tokyo) Biological Functions of MSC & Its Progenies Session 3 Future of Stratified Medicine (Organized by Kyowa Hakko Kirin Co., Ltd.) 13:10 ~ 15:00 Chairpersons: Surapol Issaragrisil, Kun-Soo Lee, Shigetaka Asano 13:10 ~ 13:50 1. Kazuhiro Sakurada (Sony CSL) Open Innovation Platform for Predictive and Preventive Medicine 2. Kunio Shiota (The University of Tokyo) Environmental Epigenetics 3. Shigetaka Asano (Waseda University and Kobe University) Promotion of P4 Healthcare / Medicine using MSCs 13:50~ 14:30 14:30 ~ 15:00 10

12 Session 4 Round Discussion For Hybrid MSC Bank Network (Organized by TNP Partners Corporation, StemCell Institute) 15:10 ~ 17:30 Chairpersons: Tran Van Binh, Dong-Tsamn Lin, Tsuneo A. Takahashi 15:10 ~ 15:40 1. Tsuneo A. Takahashi (Institute for Frontier Medical Sciences, Kyoto University) Bridge between public and private cord blood banks: potential of a mesenchymal stem cell hybrid bank 2. Current Status & Future Direction: Jay Lee (MEDIPOST) Evolution from the cord blood to the stem cell therapeutics Kate Brown (Cord Blood Registry (CBR)) Cryopreservation of Umbilical Cord Tissue at a Private Cord Blood Bank. 3. General Comment: Cladd E. Stevens (Memorial Sloan Kettering Cancer Center, NY) Tsuneo A. Takahashi (Institute for Frontier Medical Sciences, Kyoto University) 15:40 ~ 16:20 16:20 ~ 17:00 17:00 ~ 17:30 DAY II SCIENTIFIC PROGRAM HIGHLIGHTS 11

13 12 MEMO

14 Presidential Lecture ABSTRACT & CURRICULUM VITAE

15 Surapol Issaragrisil MD, FRCP, FACP, FRCPA, FRCPath Position - Professor of Medicine, Division of Hematology Department of Medicine, Faculty of Medicine Siriraj Hospital Mahidol University, Bangkok, Thailand - Director, Chulabhorn Bone Marrow Transplant Center - Director, Center of Excellence for Stem Cell Research - Fellow of Royal Institute (Thailand), Academy of Science Education - MD, Faculty of Medicine Siriraj Hospital Research Fellow, Department of Clinical Physiology, University of Ulm, Germany Clinical Fellow, Fred Hutchinson Cancer Research Center University of Washington, Seattle USA 1985 Membership and Fellowship Fellow of the Royal College of Physicians (London) Fellow of American College of Physicians Fellow of Royal College of Pathologists of Australasia Fellow of Royal College of Pathologists (UK) Member of American Society of Hematology, International Society for Experimental Hematology, American Association for Advancement of Science, International Society of Hematology, International Society for Hematotherapy and Graft Engineering, British Society of Hematology, Asian Conferences on Modern Therapy in Hematology Honors and Awards Quality Person of the Year 2012 in Medicine National Outstanding Person in Science and Technology Dushdi Mala Medal for Innovation in Medicine 2008 Mahidol University Award for Outstanding Research 2008 Senior Research Scholar of Thailand Research Fund, 2005 Organizing the Humboldt Kolleg, The Role of Science to Improve Quality of Life in Postgenomic Era, 2003 President of Asia Pacific Bone Marrow Transplant Group, 2000 The National Heart, Lung, and Blood Institute Award 1998 for Outstanding Commitment and Dedication in Promoting Joint Research in US-Thailand Collaboration on Aplastic Anemia National Best Research Award from National Research Council, 1993, 1995 Mahidol University-B-Braun Prize for Medical Research 1993 Publications 119 papers (84 in international journals) 25 Book Chapters 14

16 AsiaCORD: History and the Future Surapol Issaragrisil Division of Hematology, Department of Medicine, Chulaborn Bone Marrow Transplant Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand AsiaCORD is an International organization which aims to help countries in Asia for establishing internationally standardized cord blood banks in Asian cities and to fasten search and supply high quality cord blood sample for patients in Asia. AsiaCORD was established in November 2000 in Bangkok by Professor Shigetaka Asano from Tokyo together with hematologists from Japan, China, Korea, Taiwan, Thailand and Vietnam. Activities of AsiaCORD were to established AsiaCORD standards in November, 2011 and to certify cord blood bank in Asian cities including Beijing (December 1, 2001), Tienjin (December 2, 2001), Tokyo (June 28, 2002) and Seoul (August 28, 2002) As patients and physicians can now contact reliable any cord blood banks directly and obtain cord blood samples more easily. The activities of AsiaCORD are gradually shifting towards sharing advanced scientific knowledge and technology for all banking and transplantation by having Annual AsiaCORD meeting for Advance in Cell Therapy Recent progresses in the field of cord blood banking and transplantation include establishment of public/private hybrid cord blood bank, the use of double cord blood, haploidentical and mismatched transplantation. Other than cord blood stem cell transplantation, umbilical cord blood can be used for cellular therapy such as cord blood derived natural killer cells, cord blood T regulatory cells, umbilical cord blood derived multivirus specific CTLs for therapeutic use. Umbilical cord blood contains mesenchymal stem cells which are non-hematopoietic multipotent stem cells and have capacity to differentiate to mesodermal lineage including osteocyte, chondrocyte, adipocyte and ectodermal lineage (neurocyte) and endodermal lineage (hepatocyte). Mesenchymal stem cells have an immunomodulatory property, can release cytokines and can regulate microenvironment in the host tissues. Mesenchymal stem cells can be transplanted across HLA barrier. Mesenchymal stem cells from umbilical cord blood can be therefore potentially used in the field of regenerative medicine. 15

17 16 MEMO

18 Session 1-1, 1-2 Immune Dysfunctions after HSCT ABSTRACTS & CURRICULUM VITAE

19 Eun-Suk Kang, M. D., Ph. D. Nationality Republic of Korea Address 81 Irwon-ro, Gangnam-gu, Seoul, Korea TEL FAX Field of Reserch Immunology Education Ewha Womans University, Collage of Medicine, Seoul, Korea (M.D.) Doctor of Medical Science Faculty of Medicine, Ulsan University, Collage of Medicine, Postgraduate School, Seoul, Korea (M.S. / Ph. D.) Professional Experience Resident in Clinical Pathology, Asan Medical Center of Ulsan University, Seoul, KOREA Clinical Fellow in Clinical Pathology, Ewha Womans University Hospital, Seoul, KOREA Post-doctoral Fellow in Transplantation Immunology, TBRC, MGH, Harvard Medical School, Boston, MA, U.S.A Assistant Professor in Laboratory Medicine, Ewha Womans University Hospital, Seoul, Korea Research scholar in Pathology, Stanford University, CA, USA Associate Professor in Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea 2014-present Professor in Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea Recent Related Publications (within 5 Papers) 1. Lee KH, Jung SK, Kim SJ, Jang JH, Kim K, Kim WS, Jung CW, Kim DW, Kang ES. Incidence and risk factors of poor mobilization in adult autologous peripheral blood stem cell transplantation: a single-centre experience. Vox Sang Nov;107(4): Sung KW, Chueh HW, Lee NH, Kim DH, Lee SH, Yoo KH, Koo HH, Kang ES, Kim DW. Optimal time to start peripheral blood stem cell collection in children with high-risk solid tumors. J Korean Med Sci Jan;29(1): Son MH, Kim DH, Lee SH, Yoo KH, Sung KW, Koo HH, Kim JY, Cho EJ, Kang ES, Kim DW. Hematologic recovery after tandem high-dose chemotherapy and autologous stem cell transplantation in children with high-risk solid tumors. J Korean Med Sci Feb;28(2): doi: /jkms Jung H, Ki CS, Kim JW, Kang ES. Frequencies of 10 autosomal minor histocompatibility antigens in Korean population and estimated disparities in unrelated hematopoietic stem cell transplantation. Tissue Antigens Jan;79(1):

20 An Overview of Immune Reconstitution after Hematopoietic Stem Cell Transplantation Eun-Suk Kang Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine Hematopoietic stem cell transplantation(hsct) is a critical treatment modality in patients with various diseases including hematologic malignancies. The goal of HSCT is the restoration of hematopoietic and functional immune systems through engraftment of hematopoietic progenitor cells and transfer of functional immune cells. However, HSCT itself would bring about inevitable side effects such as graft versus host disease and infections such as Cytomegalovirus in many patients, mainly due to immunological barriers and insufficient immune reconstitutions. Many studies have shown the variables affecting on immune reconstitution, including recipient s factor such as age, diagnosis, previous treatments and conditioning regimens and donor factors such as histocompatibility, source of HSCs and manipulation of grafts. In particular, the transfer of donor immunity against pathogens or tumor antigens to recipient became one of the important concerns recently. The means of measuring proper immune reconstitution after HSCT to predict the clinical outcome have been extensively reported. Quantitative analyses of lymphocyte subsets including regulatory T cells(treg) and naïve and memory cells would be the most approachable test in clinical setting. However, measurement of specific immune response such as CMV-specific T cells by means of cytokine analysis would provide more accurate information for clinical interpretation. Also molecular approaches quantitating T-cell receptor excision circles(trec), immunoglobulin κ-deleting recombination excision circles(krec) or Treg-specific demethylated region(tsdr) would provide better insights for the development of functional immune systems. In this talk, I would present the overview of immune reconstitution after HSCT and share the immune monitoring data from adult allogeneic HSCT patients at my hospital. 19

21 Yousuke Takahama, Ph. D. Nationality Japanese Address Hachiman-nijo, Tokushima , Japan Telephone Field of Reserch Immunology Education Faculty of Science, Tokyo Institute of Technology Graduate School of Medicine, Osaka University (Ph. D.) Professional Experience JSPS Junior Fellow, Osaka University Medical School, Japan Research Fellow, Osaka University Medical School, Japan Visiting Fellow, National Cancer Institute, USA Visiting Associate, National Cancer Institute, USA Research Group Leader, Syntex Institute of Immunology, Japan Assistant Professor, University of Tsukuba, Japan PRESTO Investigator, JST, Japan Team Director, RIKEN Center for Allergy and Immunology, Japan 1999-present Professor, Institute for Genome Research, University of Tokushima, Japan Recent Related Publications (within 5 Papers) 1. Takada K, Takahama Y. Positive selection-inducing self-peptides displayed by cortical thymic epithelial cells. Adv Immunol. 125: (2015). 2. Ohigashi I, Zuklys S, Sakata M, Mayer CE, Zhanybekova S, Murata S, Tanaka K, Hollander GA, Takahama Y. Aireexpressing thymic medullary epithelial cells originate from β5t-expressing progenitor cells. Proc Natl Acad Sci USA. 110: (2013). 3. Nitta T, Murata S, Sasaki K, Fujii H, Mat Ripen A, Ishimaru N, Koyasu S, Tanaka K, Takahama Y. Thymoproteasome shapes immunocompetent repertoire of CD8+ T cells. Immunity. 32:29-40 (2010) 4. Hikosaka Y, Nitta T, Ohigashi I, Yano K, Ishimaru N, Hayashi Y, Matsumoto M, Matsuo K, Penninger JM, Takayanagi H, Yokota Y, Yamada H, Yoshikai Y, Inoue J, Akiyama T, Takahama Y. The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. Immunity. 29: (2008). 5. Takahama Y. Journey through the thymus: stromal guides for T-cell development and selection. Nat Rev Immunol. 6: (2006). 20

22 T cell formation in thymus microenvironments Yousuke Takahama Division of Experimental Immunology, Institute for Genome Research, University of Tokushima During development in the thymus, newly generated repertoire of diverse TCR-αβ recognition specificities in immature T cells is selected to form the functionally competent and self-tolerant repertoire of mature T cells. Positive selection supports the survival of potentially useful self-mhc-restricted thymocytes upon low-affinity TCR engagement, whereas negative selection deletes potentially harmful self-reactive thymocytes upon high-affinity TCR engagement. Recent advances in the biology of thymic stromal cells have indicated that T cell formation in the thymus requires positive selection by thymic cortical epithelial cells that express unique protein degradation machineries, including the β5tcontaining thymoproteasome. It has also been revealed that the proximal interplay among developing T cells, dendritic cells, and medullary epithelial cells that promiscuously express tissue-specific selfantigens is essential for the establishment of self-tolerant TCR repertoire and the generation of regulatory T cells. These results suggest the vital roles played by self-peptides specifically expressed by multiple thymic microenvironments in the development of functionally competent and self-tolerant T cells. 21

23 Satoshi TAKAHASHI, M. D., Ph. D. Nationality Japanese Address Division of Molecular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo (IMSUT) 6-1 Shirokanedai-4, Minato-ku, Tokyo , Japan TEL (ext.75053) FAX Field of Reserch Hematology Education M. D., Iwate Medical University, School of Medicine. Professional Experience : Clinical fellow, Department of Internal Medicine, IMSUT and 2002-present: Chief, BMT Program, IMSUT : Research fellow, Center for Cell and Gene Therapy, Baylor Collage of Medicine, Houston, Texas, USA : Assistant Professor/ Lecturer, Department of Hematology and Oncology, IMSUT 2005-present: Associate Professor, Division of Molecular therapy, Advanced Clinical Research Center, IMSUT Recent Related Publications (within 5 Papers) 1. Takahashi S. Here comes the cord. Blood Res.49(4):209-10, doi: /br Konuma T, Ooi J, Uchida N, Ogawa H, Ohashi K, Kanamori H, Aotsuka N, Onishi Y, Yamaguchi H, Kozai Y, Nagamura-Inoue T, Kato K, Suzuki R, Atsuta Y, Kato S, Asano S, Takahashi S. Granulocyte colony-stimulating factor combined regimen in cord blood transplantation for acute myeloid leukemia: a nationwide retrospective analysis in Japan. Haematologica Dec;99(12):e doi: /haematol Epub 2014 Sep Takahashi S*, N Watanabe*, Ishige M, et al. Dynamic analysis of chimerism after HLA-mismatched cord blood transplantation elucidated by 9-color FACS: implications for early detection of engraftment failure and relapse. Biol Blood Marrow Transplant, 14(6): , Takahashi S, Ooi J, Tomonari A, et al. Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem cell transplantation from related donors in adult patients with hematological malignancies after myeloablative conditioning regimen. Blood, 109: , Takahashi S, Iseki T, Ooi J, et al. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematological malignancies. Blood 104: ,

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