Research

Department of Cell Processing and Transfusion

Associate Professor Tokiko Nagamura-Inoue, M.D., D.M.Sc.
　　
　Assistant Profissor Toyotaka Kawamata, M.D., D.M.Sc.
　　
　Post-dcotoral fellow Mayuko Tsuda, M.D., D.M.Sc.
　　

　Our department was established in 1990, in order to manage the transfusion medicine and the cell processing for hematopoietic stem cell transplantation. Beside the transfusion medicine and testing in the hospital, our department has been supported translational research and managed IMSUT-Cell Resource Center (IMSUT-CRC), which has been established in 1997. Recent our projects include Research CB Stem Cells Bank as National Bioresource Project (NBRP) supported by AMED(MEXT) and CB and umbilical cord (UC)-derived mesenchymal stem/stromal cell banking (IMSUT CORD) for clinical use supported by AMED(MHLW). In this stdy, we developed immunosuppressive therapy for severe GVHD after hematopoietic stem cell transplantation using UC-MSCs and expanded regulatory T cells from CB and adult blood. We also explore the clinical application of UC-MSC for newborn encephalopathy, some of which develop to cerebral palsy.


1. Umbilical Cord-derived mesenchymal stem/stromal cells banking (IMSUT-CORD):
Nagamura-Inoue T, Tsuda M. Mori Y, Takahashi A, Shimazu T, Mukai T, Tojo A.
Umbilical cord (UC) is a rich source of mesenchymal stem cells (MSCs). The UC is normally discarded after birth and its collection does not require an invasive procedure with ethical concerns. Moreover, UC-derived MSCs (UC-MSCs) possess many advantageous features, namely high frequency, pluripotency, high proliferation capacity, immunomodulatory properties and no donor age-dependent variations. We have studied these characteristics and efficient expansion system of UC-MSCs, in order to apply the regenerative medicine and immunotherapy, supported by MHLW. UC-MSCs have the potential to inhibit the activated T cell proliferation upon the allogeneic stimulations, suggesting the clinical possibility to apply those for the GVHD treatment. Our final goal is to establish the CB and UC-MSCs banking for clinical use.
2. Toward Investigator-sponsored IND (Investigation New Drug application) of allogeneic umbilical cord-derived mesenchymal stromal cells for severe acute graft-versus –host disease.
Nagamura-Inoue T, Tsuda M. Mori Y, Takahashi A, Shimazu T, Mukai T, Tojo A.
The present study aims, through a corporate collaboration, to process umbilical cord-derived mesenchymal stromal cells (UC-MSC) as a product for applications such as regenerative medicine, and perform an investigator-initiated clinical trial (phase I) against Grade III-IV severe acute graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT). Severe acute GVHD negatively influences the prognosis of HSCT, where the long-term survival rate in cases of steroid resistance is extremely low. In 2015, bone marrow (BM)-derived MSCs were reported to be effective against the severe acute GVHD and were commercially introduced; however, these are derived from imported BM and are expensive. The UC-MSC proposed here are intrinsically adhesive, and have defined phenotypes of MSC and differentiation potency. Moreover, their traceability is high due to their domestic origin; harvesting them confers no physical burden on the donor; and they have high proliferative potential and alloimmune suppressive capacity. They also have low antigenicity, and because they are treated as medical waste, ethical obstacles are few and they can be easily and widely obtained. We were the first to report on UC-MSC of domestic origin, and we developed efficient MSC recovery methods and a serum-free cryoprotectant based on cord tissue cryopreservation and improved explant methods. Furthermore, by culturing with serum-free medium (RM medium; Rohto Pharmaceuticals), we achieved serum-free manufacture from harvest to cryopreservation. In 2016, through strategic pharmaceutical consultation with the Pharmaceuticals and Medical Devices Agency (PMDA), we reached an agreement not only regarding a clinical trial, but also regarding quality/safety, and aspects of production unrelated to the trial. Presently, although non-clinical safety tests and some virus testing are still ongoing, reports on these tests will soon be available, and we are scheduled to commence the investigator-initiated clinical trial within the 2017 fiscal year.
3. Therapeutic potential of Umbilical cord-derived mesenchymal stromal cells to the cerebral palsy.
Mukai T, Shimazu T, Mori Y, Takahashi A, Nagamura-Inoue T.
Previous studies have been reported that MSCs have self-renewal capacity, multi-lineage differentiation potential and the ability to migrate toward sites of inflammation or injury. The potential of MSCs for transdifferentiating into not only mesoderm lineage but also endoderm and ectoderm, including the neural lineage, has enhanced the clinical application of MSCs for regenerative medicine including neurological disorders. We reported here that the umbilical cord-derived mesenchymal stromal cells (UC-MSCs) had the potential of neurogenic differentiation. Furthermore, the neurogenic lineage genes expressed more in differentiation via neurosphere formation with higher expresion of ES markers. The migration ability to damaged cells was not influenced by the neurosphere formation with or without differentiationinto neurogenic cells. Now newborn mice models mimicking cerebral palsy is under investigation. in vivo.
4. Expansion of regulatory T cell therapy for GVHD, transplantation, and autoimmune diseases.
Nagamura-Inoue T, Ichimura S, Ogami K, Tojo A.
Regulatory T cells harbored the immunosuppressive effects and were related to the pathogenesis of graft-versus-host disease (GVHD), rejection of organ transplantation and autoimmune disease. We developed the system of ex vivo expansion of CD25+FOXP3+regulatory T cells using mTOR inhibitor, from the small amount of CD4+peripheral blood and also cord blood (CB), to apply the immunological therapy.
5. Research Cord Blood Stem Cell Bank/National BioResouce Project (NBRP) (IMSUT-Cell Resource Center):
Nagamura-Inoue T, Ichimura S, Takahashi A. Hori A, Shimazu T, Ueda M.
“Research Cord Blood Stem Cell Bank” (former named ‘Research Stem Cell Resource Bank’) was established supported by MEXT for the development of the medicine including Regenerative Medicine and drug discovery in Japan since 2004. Since 2012, July, this project has been incorporated in National BioResouce Project (NBRP). The research CB bank provides processed and cryopreserved CB units which are non-conforming for clinical use, to world-wide researchers via RIKEN Bioresource Center. Visit our website http://www.nbrp.jp/.
6. Management of Institute of Medical Science, University of Tokyo-Cell Resource Center (IMSUT-CRC):
Nagamura-Inoue T, Takahashi A., Shimazu T., Ogami K, Tojo A
To promote the cell therapy in translational researches, IMSUT-Cell Resource Center (IMSUT-CRC) has been established in 1997 (originally called as Room for Clinical Cellular Technology (RCCT)). Until now, the following projects had implemented; 1) CB cell processing for banking（1997-2008） (for Tokyo Cord Blood Bank, Research cord blood stem cell bank, and related sibling donors), 2) Dendritic cell therapies (1998-2001), 3) Regenerative therapy of alveolar bone derived from bone marrow mesenchymal cells (2005-2011), 4) Gene therapy for renal cancer (1998), 5) CB and UC-MSCs banking (IMSUT-CORD) (2012-present), 6) Regenerative medicine for hemophilia arthropathy using autologous bone marrow-derived MSC (in preparation).

Publications

  1. Mukai T, Mori Y, Shimazu T, Takahashi A, Tsunoda H, Yamaguchi S, Kiryu S, Tojo A, Nagamura-Inoue T.Intravenous injection of umbilical cord-derived mesenchymal stromal cells attenuates reactive gliosis and hypomyelination in a neonatal intraventricular hemorrhage model. Neuroscience. Jul 4;355:175-187, 2017.
  2. Nagamura-Inoue T, Mukai T. Umbilical Cord is a Rich Source of Mesenchymal Stromal Cells for Cell Therapy. Current Stem Cell Research & Therapy, 11, 634-642,2016
  3. Itonaga H, Iwanaga M, Aoki K, Aoki J, Ishiyama K, Ishikawa T, Sakura T, Fukuda T, Najima Y, Yujiri T, Mori T, Kurokawa M, Nawa Y, Uchida N, Morishita Y, Hashimoto H, Eto T, Hirokawa M, Morishima Y, Nagamura-Inoue T, Atsuta Y, Miyazaki Y. Impacts of graft-versus-host disease on outcomes after allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia: A nationwide retrospective study. Leuk Res. 2015 Dec 24. doi: 10.1016/j.leukres.2015.12.009. [Epub ahead of print]
  4. Yanada M, Kanda J, Ohtake S, Fukuda T, Sakamaki H, Miyamura K, Miyawaki S, Uchida N, Maeda T, Nagamura-Inoue T, Asou N, Morishima Y, Atsuta Y, Miyazaki Y, Kimura F, Kobayashi Y, Takami A, Naoe T, Kanda Y. Unrelated bone marrow transplantation or immediate umbilical cord blood transplantation for patients with acute myeloid leukemia in first complete remission. Eur J Haematol. Dec 18. doi: 10.1111/ejh.12723. [Epub ahead of print], 2015.
  5. Terakura S, Atsuta Y, Tsukada N, Kobayashi T, Tanaka M, Kanda J, Najima Y, Fukuda T, Uchida N, Takahashi S, Nagamura-Inoue T, Morishima Y, Miyamura K. Japan Society for Hematopoietic Cell Transplantation, Comparison of Outcomes of 8/8 and 7/8 Allele-Matched Unrelated Bone Marrow Transplantation and Single-Unit Cord Blood Transplantation in Adults with Acute Leukemia. Biol Blood Marrow Transplant. 2015 Oct 22. pii: S1083-8791(15)00676-X. doi: 10.1016/j. bbmt.2015.10.006. [Epub ahead of print], 2015.
  6. Mori J, Ishiyama K, Yamaguchi T, Tanaka J, Uchida N, Kobayashi T, Fukuda T, Kanamori H, Miyamura K, Takahashi S, Eto T, Hirokawa M, Mori S, Nagamura T, Atsuta Y, Takami A. Outcomes of allogeneic hematopoietic cell transplantation in patients with biphenotypic acute leukemia. Ann Hematol. 2015 Oct 26. [Epub ahead of print]
  7. Mukai T, Nagamura-Inoue T, Shimazu T, Mori Y, Takahashi A, Tsunoda H, Yamaguchi S, Tojo A. Neurosphere formation enhances the neurogenic differentiation potential and migratory ability of umbilical cord-mesenchymal stromal cells. Cytotherapy. 18:229-241, 2016.
  8. Nishiwaki S, Imai K, Mizuta S, Kanamori H, Ohashi K, Fukuda T, Onishi Y, Takahashi S, Uchida N, Eto T, Nakamae H, Yujiri T, Mori S, Nagamura-Inoue T, Suzuki R, Atsuta Y, Tanaka J. Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph+ALL: a study from the adult ALL WG of the JSHCT. Bone Marrow Transplant. 51:43-50, 2016.
  9. Arai Y, Kanda J, Nakasone H, Kondo T, Uchida N, Fukuda T, Ohashi K, Kaida K, Iwato K, Eto T, Kanda Y, Nakamae H, Nagamura-Inoue T, Morishima Y, Hirokawa M, Atsuta Y, Murata M. Risk factors and prognosis of hepatic acute GvHD after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 51:96-102, 2016.
  10. Nakane T, Fukuda T, Kanda J, Taniguchi S, Eto T, Ohashi K, Nakamae H, Kurokawa M, Mori T, Morishima Y, Nagamura-Inoue T, Sakamaki H, Atsuta Y, Murata M. Age influences post-graft-versus-host disease non-relapse mortality in adults with acute graft-versus-host disease of varying severity following allogeneic hematopoietic cell transplant. Leuk Lymphoma. 56:2392-7, 2015.
  11. Nakasone H, Fukuda T, Kanda J, Mori T, Yano S, Kobayashi T, Miyamura K, Eto T, Kanamori H, Iwato K, Uchida N, Mori S, Nagamura-Inoue T, Ichinohe T, Atsuta Y, Teshima T, Murata M. Impact of conditioning intensity and TBI on acute GVHD after hematopoietic cell transplantation. Bone Marrow Transplant. 50:559-65, 2015.
  12. He H. Nagamura-Inoue T., Takahashi A., Mori Y., Shimazu T., Tsunoda H., Tojo A. Immunosuppressive properties of Wharton's jelly-derived mesenchymal stromal cells in Vitro, Int J Hematol..in press, 2015
  13. Shimazu T, Mori Y, Takahashi A, Tsunoda H, Tojo A, Nagamura- Inoue T, Serum- and Xeno-free Cryopreservation of Human umbilical cord tissue as mesenchymal stromal cell source, Cytotherapy, 17,593-600, 2015, DOI: http://dx.doi.org/10.1016/j.jcyt.2015.03.604
  14. Mori Y, Ohshimo J, Shimazu T, He H, Takahashi A, Yamamoto Y, Tsunoda H, Tojo A, Nagamura-Inoue T. Improved Explant Method To Isolate Umbilical Cord-derived Mesenchymal Stem Cells And Their Immunosuppressive Properties.　 Tissue Eng Part C Methods. 21,1-6, 2014, DOI: 10.1089/ten.tec.2014.0385
  15. 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. 99,e264-8,2014
  16. Ohashi K, Nagamura-Inoue T, Nagamura F, Tojo A, Miyamura K, Mori T, Kurokawa M, Taniguchi S, Ishikawa J, Morishima Y, Atsuta Y, Sakamaki H.　Effect of graft sources on allogeneic hematopoietic stem cell transplantation outcome in adults with chronic myeloid leukemia in the era of tyrosine kinase inhibitors: a Japanese Society of Hematopoietic Cell Transplantation retrospective analysis. Int J Hematol. 100, 296-306,2014
  17. He H. Nagamura-Inoue T., Tsunoda H., Yuzawa M., Yamamoto Y., Yorozu P., Agata H., Tojo A. Stage-Specific Embryonic Antigen 4 in Wharton’s Jelly-derived mesenchymal stem cells is not a marker for proliferation and multipotency. Tissue Engineering., Tissue Eng Part A. 20,1314-24,2014. DOI: 10.1089/ten.tea.2013.0333
  18. Sakabe S, Takano R, Nagamura-Inoue T, Yamashita N, Nidom CA, Quynh Le MT, Iwatsuki-Horimoto K, Kawaoka Y . Differences in Cytokine Production in Human Macrophages and in Virulence in Mice Are Attributable to the Acidic Polymerase Protein of Highly Pathogenic Influenza A Virus Subtype H5N1. J Infect Dis. 207:262-71, 2013
  19. Ebihara Y, Takedani H, Ishige I, Nagamura-Inoue T, Wakitani S, Tojo A, Tsuji K.　Feasibility of autologous bone marrow mesenchymal stem cells cultured with autologous serum for treatment of haemophilic arthropathy.　Haemophilia. 19:e87-9, 2013.
  20. Sakabe S, Iwatsuki-Horimoto K, Takano R, Nidom CA, Le MQ, Nagamura-Inoue T, Horimoto T, Yamashita N, Kawaoka Y. Cytokine production by primary human macrophages infected with highly pathogenic H5N1 or pandemic H1N1 2009 influenza viruses. J Gen Virol. 92:1428-34, 2011
  21. Ishige I., Nagamura-Inoue T., Honda J.M, Harnprasopwat R., Kido M., Sugimoto M., Nakauchi H, Tojo A. Comparison of mesenchymal stem cells derived from arterial, venous, and Wharton’s jelly explants of human umbilical cord. Int J Hematol, 90:261-9, 2009.
  22. Konuma T, Takahashi S, Ooi J, Tomonari A, Tsukada N, Kato S, Sato A, Monma F, Kasahara S, Nagamura-Inoue T, Uchimaru K, Iseki T, Tojo A, Yamaguchi T, Asano S. Myeloablative unrelated cord blood transplantation for acute leukemia patients between 50 and 55 years of age: single institutional retrospective comparison with patients younger than 50 years of age. Ann Hematol. 88:581-8,2009.
  23. Nagamura-Inoue T, Kai S, Azuma H, Takanashi M, Isoyama K, Kato K, Takahashi S, Taniguchi S, Miyamura K, Aoki K, Hidaka M, Nagamura F, Tojo A, Fang X, Kato S; Japan Cord Blood Bank Network. Unrelated cord blood transplantation in CML: Japan Cord Blood Bank Network analysis. Bone Marrow Transplant. 42:241-51, 2008
  24. Konuma T, Ooi J, Takahashi S, Tomonari A, Tsukada N, Kobayashi T, Sato A, Kato S, Kasahara S, Ebihara Y, Nagamura-Inoue T, Tsuji K, Tojo A, Asano S. Cardiovascular toxicity of cryopreserved cord blood cell infusion. Bone Marrow Transplant. 41:861-5.2008
  25. Nakayama S, Nagamura-Inoue T, Yokoyama K, Ohno K, Ooi J, Takahashi S, Uchimaru K, Iseki T, Tojo A. Cytogenetic remissions induced by interferon- and imatinib mesylate are immunologically distinct in chronic myeloid leukemia. Int J Hematol. 86:208-211, 2007.
  26. Nagamura-Inoue T, Kodo H, Takahashi T, Mugishima H, Tojo A, Asano S. Four cases of donor cell-derived AML following unrelated cord blood transplantation for adult patients: experiences of the Tokyo Cord Blood Bank. Cytotherapy. 4:1-2,2007
  27. Okada H, Nagamura-Inoue T, Mori Y, Takahash TA. Expansion of Valpha24Vbeta11 NKT cells from cord blood mononuclear cells using Interleukin-15, IL-7 and Flt3-L depends on monocytes. Eur J Immunol. 36:236-244, 2006
  28. Yasutake, M, Zheng Y, Nagamura-Inoue, T, Akagawa E, Tokushima Y, Terashima S, Takahashi TA. SCID-Repopulating activity of human umbilical cord blood-derived hematopoietic stem/progenitor cells in a nonobese diabetic/Schi-SCID mice serial xenoransplantation model and immune cell activities in vitro: a comparative study of the filter method and the HES method, Transfusion. Transfusion. 45:1899-908, 2005.
  29. Nagamura-Inoue T, Mori Y, Zheng Y, Watanabe N, Takahashi TA. Differential expansion of umbilical cord blood mononuclear cell derived natural killer cells dependent on the dose of Interleukin 15 with Flt3L. Exp Hematol 32:202-209, 2004.

BIBLIOGRAPHY

  1. Mori Y, Ohshimo J, Shimazu T, He H, Takahashi A, Yamamoto Y, Tsunoda H, Tojo A, Nagamura-Inoue T.　Improved Explant Method To Isolate Umbilical Cord-derived Mesenchymal Stem Cells And Their Immunosuppressive Properties.　 Tissue Eng Part C Methods. 2014 Sep 13. [Epub ahead of print]
  2. 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.　
  3. Ohashi K, Nagamura-Inoue T, Nagamura F, Tojo A, Miyamura K, Mori T, Kurokawa M, Taniguchi S, Ishikawa J, Morishima Y, Atsuta Y, Sakamaki H.　Effect of graft sources on allogeneic hematopoietic stem cell transplantation outcome in adults with chronic myeloid leukemia in the era of tyrosine kinase inhibitors: a Japanese Society of Hematopoietic Cell Transplantation retrospective analysis.　Int J Hematol. 2014 Sep;100(3):296-306. doi: 10.1007/s12185-014-1632-9. Epub 2014 Aug 2.
  4. He H. Nagamura-Inoue T., Tsunoda H., Yuzawa M., Yamamoto Y., Yorozu P., Agata H., Tojo A. Stage-Specific Embryonic Antigen 4 in Wharton’s Jelly-derived mesenchymal stem cells is not a marker for proliferation and multipotency. Tissue Engineering., Tissue Eng Part A. 20,1314-24,2014
  5. Atsuta Y, Suzuki R, Yamashita T, Fukuda T, Miyamura K, Taniguchi S, Iida H, Uchida T, Ikegame K, Takahashi S, Kato K, Kawa K, Nagamura-Inoue T, Morishima Y, Sakamaki H, Kodera Y; Japan Society for Hematopoietic Cell Transplantation, Continuing increased risk of oral/esophageal cancer after allogeneic hematopoietic stem cell transplantation in adults in association with chronic graft-versus-host disease. Ann Oncol. 25,435-41.,2014
  6. Murata M, Nishida T, Taniguchi S, Ohashi K, Ogawa H, Fukuda T, Mori T, Kobayashi H, Nakaseko C, Yamagata N, Morishima Y, Nagamura-Inoue T, Sakamaki H, Atsuta Y, Suzuki R, Naoe T. Allogeneic transplantation for primary myelofibrosis with BM, peripheral blood or umbilical cord blood: an analysis of the JSHCT. Bone Marrow Transplant. 49, 355-60,2014
  7. Kanda J, Nakasone H, Atsuta Y, Toubai T, Yokoyama H, Fukuda T, Taniguchi S, Ohashi K, Ogawa H, Eto T, Miyamura K, Morishima Y, Nagamura-Inoue T, Sakamaki H, Murata M. Risk factors and organ involvement of chronic GVHD in Japan. Bone Marrow Transplant. 49,228-35,2014
  8. Kanamori H, Mizuta S, Kako S, Kato H, Nishiwaki S, Imai K, Shigematsu A, Nakamae H, Tanaka M, Ikegame K, Yujiri T, Fukuda T, Minagawa K, Eto T, Nagamura-Inoue T, Morishima Y, Suzuki R, Sakamaki H, Tanaka J.　Reduced-intensity allogeneic stem cell transplantation for patients aged 50 years or older with B-cell ALL in remission: a retrospective study by the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation.　 Bone Marrow Transplant. 48,1513-8,2013
  9. Murata M, Nakasone H, Kanda J, Nakane T, Furukawa T, Fukuda T, Mori T, Taniguchi S, Eto T, Ohashi K, Hino M, Inoue M, Ogawa H, Atsuta Y, Nagamura-Inoue T, Yabe H, Morishima Y, Sakamaki H, Suzuki R.　 Clinical Factors Predicting the Response of Acute Graft-versus-Host Disease to Corticosteroid Therapy: An Analysis from the GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation.　 Biol Blood Marrow Transplant. 19,1183-9, 2013
  10. Kurosawa S, Yakushijin K, Yamaguchi T, Atsuta Y, Nagamura-Inoue T, Akiyama H, Taniguchi S, Miyamura K, Takahashi S, Eto T, Ogawa H, Kurokawa M, Tanaka J, Kawa K, Kato K, Suzuki R, Morishima Y, Sakamaki H, Fukuda T. Recent decrease in non-relapse mortality due to GVHD and infection after allogeneic hematopoietic cell transplantation in non-remission acute leukemia. Bone Marrow Transplant. 48, 1198-22, 2013
  11. Nakasone H, Kanda J, Yano S, Atsuta Y, Ago H, Fukuda T, Kakihana K, Adachi T, Yujiri T, Taniguchi S, Taguchi J, Morishima Y, Nagamura T, Sakamaki H, Mori T, Murata M 　A case-control study of bronchiolitis obliterans syndrome following allogeneic hematopoietic stem cell transplantation; GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation.　Transpl Int. 26, 631-9, 2013
  12. Nakasone H, Kurosawa S, Yakushijin K, Taniguchi S, Murata M, Ikegame K, Kobayashi T, Eto T, Miyamura K, Sakamaki H, Morishima Y, Nagamura T, Suzuki R, Fukuda T.　Impact of hepatitis C virus infection on clinical outcome in recipients after allogeneic hematopoietic cell transplantation.Am J Hematol. 88,144-6, 2013
  13. Atsuta Y, Kanda J, Takanashi M, Morishima Y, Taniguchi S, Takahashi S, Ogawa H, Ohashi K, Ohno Y, Onishi Y, Aotsuka N, Nagamura-Inoue T, Kato K, Kanda Y. Different effects of HLA disparity on transplant outcomes after single-unit cord blood transplantation between pediatric and adult patients with leukemia. Haematologica. 98,814-22, 2013.
  14. Sakabe S, Takano R, Nagamura-Inoue T, Yamashita N, Nidom CA, Quynh Le MT, Iwatsuki-Horimoto K, Kawaoka Y . Differences in Cytokine Production in Human Macrophages and in Virulence in Mice Are Attributable to the Acidic Polymerase Protein of Highly Pathogenic Influenza A Virus Subtype H5N1. J Infect Dis. 207:262-71, 2013
  15. Ishiyama K, Takami A, Kanda Y, Nakao S, Hidaka M, Maeda T, Naoe T, Taniguchi S, Kawa K, Nagamura T, Tabuchi K, Atsuta Y, Sakamaki H.　Prognostic factors for acute myeloid leukemia patients with t(6;9)(p23;q34) who underwent an allogeneic hematopoietic stem cell transplant.　Leukemia. 26:1416-9, 2012
  16. Ishiyama K, Takami A, Kanda Y, Nakao S, Hidaka M, Maeda T, Naoe T, Taniguchi S, Kawa K, Nagamura T, Atsuta Y, Sakamaki H.　Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6;9)(p23;q34) dramatically improves the patient prognosis: a matched-pair analysis.　Leukemia. 26:461-4, 2012
  17. Ebihara Y, Takedani H, Ishige I, Nagamura-Inoue T, Wakitani S, Tojo A, Tsuji K.　Feasibility of autologous bone marrow mesenchymal stem cells cultured with autologous serum for treatment of haemophilic arthropathy.　Haemophilia. 19:e87-9, 2013.
  18. Kanda J, Atsuta Y, Wake A, Ichinohe T, Takanashi M, Morishima Y, Taniguchi S, Takahashi S, Ogawa H, Ohashi K, Ohno Y, Aotsuka N, Onishi Y, Kato K, Nagamura-Inoue T, Kanda Y. Impact of the direction of HLA mismatch on transplant outcome in single unrelated cord blood transplantation. Biol Blood Marrow Transplant. 19:247-54, 2012.
  19. Kurosawa S, Yakushijin K, Yamaguchi T, Atsuta Y, Nagamura-Inoue T, Akiyama H, Taniguchi S, Miyamura K, Takahashi S, Eto T, Ogawa H, Kurokawa M, Tanaka J, Kawa K, Kato K, Suzuki R, Morishima Y, Sakamaki H, Fukuda T. Changes in incidence and causes of non-relapse mortality after allogeneic hematopoietic cell transplantation in patients with acute leukemia/myelodysplastic syndrome: an analysis of the Japan Transplant Outcome Registry. Bone Marrow Transplant. 48: 529-536, 2012
  20. Kanda J, Ichinohe T, Kato S, Uchida N, Terakura S, Fukuda T, Hidaka M, Ueda Y, Kondo T, Taniguchi S, Takahashi S, Nagamura-Inoue T, Tanaka J, Atsuta Y, Miyamura K, Kanda Y. Unrelated cord blood transplantation vs related transplantation with HLA 1-antigen mismatch in the graft-versus-host direction. Leukemia.27:286-94, 2012
  21. Kanda J, Hishizawa M, Utsunomiya A, Taniguchi S, Eto T, Moriuchi Y, Tanosaki R, Kawano F, Miyazaki Y, Masuda M, Nagafuji K, Hara M, Takanashi M, Kai S, Atsuta Y, Suzuki R, Kawase T, Matsuo K, Nagamura-Inoue T, Kato S, Sakamaki H, Morishima Y, Okamura J, Ichinohe T, Uchiyama T. Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study. Blood.119:2141-8. 2012
  22. Atsuta Y, Morishima Y, Suzuki R, Nagamura-Inoue T, Taniguchi S, Takahashi S, Kai S, Sakamaki H, Kouzai Y, Kobayashi N, Fukuda T, Azuma H, Takanashi M, Mori T, Tsuchida M, Kawase T, Kawa K, Kodera Y, Kato S. Comparison of unrelated cord blood transplantation and HLA-mismatched unrelated bone marrow transplantation for adults with leukemia. Biol Blood Marrow Transplant. 18:780-7, 2011
  23. Kato K, Yoshimi A, Ito E, Oki K, Hara J, Nagatoshi Y, Kikuchi A, Kobayashi R, Nagamura-Inoue T, Kai S, Azuma H, Takanashi M, Isoyama K, Kato S; for the Japan Cord Blood Bank Network. Cord Blood Transplantation from Unrelated Donors for Children with Acute Lymphoblastic Leukemia in Japan: The Impact of Methotrexate on Clinical Outcomes. Biol Blood Marrow Transplant.17:1814-21, 2011
  24. Morio T, Atsuta Y, Tomizawa D, Nagamura-Inoue T, Kato K, Ariga T, Kawa K, Koike K, Tauchi H, Kajiwara M, Hara T, Kato S; Japanese Cord Blood Bank Network.　Outcome of unrelated umbilical cord blood transplantation in 88 patients with primary　immunodeficiency in Japan.　Br J Haematol. 154: 363-72, 2011.
  25. Sakabe S, Iwatsuki-Horimoto K, Takano R, Nidom CA, Le MQ, Nagamura-Inoue T, Horimoto T, Yamashita N, Kawaoka Y. Cytokine production by primary human macrophages infected with highly pathogenic H5N1 or pandemic H1N1 2009 influenza viruses. J Gen Virol. 92:1428-34, 2011
  26. Hishizawa M, Kanda J, Utsunomiya A, Taniguchi S, Eto T, Moriuchi Y, Tanosaki R, Kawano F, Miyazaki Y, Masuda M, Nagafuji K, Hara M, Takanashi M, Kai S, Atsuta Y, Suzuki R, Kawase T, Matsuo K, Nagamura-Inoue T, Kato S, Sakamaki H, Morishima Y, Okamura J, Ichinohe T, Uchiyama T. Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study. Blood. 116:1369-76. 2010.
  27. Isoyama K, Oda M, Kato K, Nagamura-Inoue T, Kai S, Kigasawa H, Kobayashi R, Mimaya J, Inoue M, Kikuchi A, Kato S; Japan Cord Blood Bank Network.Long-term outcome of cord blood transplantation from unrelated donors as an initial transplantation procedure for children with AML in Japan. Bone Marrow Transplant. 45:69-77, 2010
  28. Ishige I., Nagamura-Inoue T., Honda J.M, Harnprasopwat R., Kido M., Sugimoto M., Nakauchi H, Tojo A. Comparison of mesenchymal stem cells derived from arterial, venous, and Wharton’s jelly explants of human umbilical cord. Int J Hematol, 90:261-9, 2009.
  29. Usuki K, Yokoyama K, Nagamura-Inoue T, Ito A, Kida M, Izutsu K, Urabe A, Tojo A. CD8+ memory T cells predominate over naïve T cells in therapy-free CML patients with sustained major molecular response. Leuk Res. 33:164-5. 2009
  30. Yazaki M, Atsuta Y, Kato K, Kato S, Taniguchi S, Takahashi S, Ogawa H, Kouzai Y, Kobayashi T, Inoue M, Kobayashi R, Nagamura-Inoue T, Azuma H, Takanashi M, Kai S, Nakabayashi M, Saito H; Japan Cord Blood Bank Network. Incidence and risk factors of early bacterial infections after unrelated cord blood transplantation. Biol. Blood Marrow Transplant. 15:439-46, 2009
  31. Atsuta Y, Suzuki R, Nagamura-Inoue T, Taniguchi S, Takahashi S, Kai S, Sakamaki H, Kouzai Y, Kasai M, Fukuda T, Azuma H, Takanashi M, Okamoto S, Tsuchida M, Kawa K, Morishima Y, Kodera Y, and Kato S, for the Japan Marrow Donor Program and the Japan Cord Blood Bank Network; Disease-specific analyses of unrelated cord blood transplant compared with unrelated bone marrow transplant in adult patients with acute leukemia. Blood. 113:1631-8, 2009
  32. Konuma T, Takahashi S, Ooi J, Tomonari A, Tsukada N, Kato S, Sato A, Monma F, Kasahara S, Nagamura-Inoue T, Uchimaru K, Iseki T, Tojo A, Yamaguchi T, Asano S. Myeloablative unrelated cord blood transplantation for acute leukemia patients between 50 and 55 years of age: single institutional retrospective comparison with patients younger than 50 years of age. Ann Hematol. 88:581-8,2009.
  33. Yoshimi A, Kojima S, Taniguchi S, Hara J, Matsui T, Takahashi Y, Azuma H, Kato K, Nagamura-Inoue T, Kai S, Kato S; Japan Cord Blood Bank Network., Unrelated cord blood transplantation for severe aplastic anemia. Biol Blood Marrow Transplant. 9:1057-63, 2008
  34. Nagamura-Inoue T, Kai S, Azuma H, Takanashi M, Isoyama K, Kato K, Takahashi S, Taniguchi S, Miyamura K, Aoki K, Hidaka M, Nagamura F, Tojo A, Fang X, Kato S; Japan Cord Blood Bank Network. Unrelated cord blood transplantation in CML: Japan Cord Blood Bank Network analysis. Bone Marrow Transplant. 42:241-51, 2008
  35. Konuma T, Ooi J, Takahashi S, Tomonari A, Tsukada N, Kobayashi T, Sato A, Kato S, Kasahara S, Ebihara Y, Nagamura-Inoue T, Tsuji K, Tojo A, Asano S. Cardiovascular toxicity of cryopreserved cord blood cell infusion. Bone Marrow Transplant. 41:861-5.2008
  36. Narimatsu H, Miyakoshi S, Yamaguchi T, Kami M, Matsumura T, Yuji K, Murashige N, Kusumi E, Kodama Y, Komatsu T, Sakamaki H, Kouzai Y, Okada M, Osugi Y, Kobayashi R, Inoue M, Takahashi S, Kai S, Kato K, Nagamura-Inoue T, Taniguchi S, Kato S; Japan Cord Blood Bank Network.Chronic graft-versus-host disease following umbilical cord blood transplantation: retrospective survey involving 1072 patients in Japan.　 Blood. 112:2579-82, 2008
  37. Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, Kato K, Tabuchi K, Tsuchida M, Morishima Y, Mitamura M, Kawa K, Kato S, Nagamura T, Takanashi M, Kodera Y. Unification of Hematopoietic Stem Cell Transplantation Registries in Japan and Establishment of the TRUMP System. Int J Hematol. 86:269-74, 2007.
  38. Nakayama S, Nagamura-Inoue T, Yokoyama K, Ohno K, Ooi J, Takahashi S, Uchimaru K, Iseki T, Tojo A. Cytogenetic remissions induced by interferon-α and imatinib mesylate are immunologically distinct in chronic myeloid leukemia. Int J Hematol. 86:208-211, 2007.
  39. Nagamura-Inoue T, Kodo H, Takahashi T, Mugishima H, Tojo A, Asano S. Four cases of donor cell-derived AML following unrelated cord blood transplantation for adult patients: experiences of the Tokyo Cord Blood Bank. Cytotherapy. 4:1-2,2007
  40. Okada H, Nagamura-Inoue T, Mori Y, Takahash TA. Expansion of Valpha24Vbeta11 NKT cells from cord blood mononuclear cells using Interleukin-15, IL-7 and Flt3-L depends on monocytes. Eur J Immunol. 36:236-244, 2006
  41. Yasutake, M, Zheng Y, Nagamura-Inoue, T, Akagawa E, Tokushima Y, Terashima S, Takahashi TA. SCID-Repopulating activity of human umbilical cord blood-derived hematopoietic stem/progenitor cells in a nonobese diabetic/Schi-SCID mice serial xenoransplantation model and immune cell activities in vitro: a comparative study of the filter method and the HES method, Transfusion. Transfusion. 45:1899-908, 2005.

Invited talks at international congress

  1. Nagamura-Inoue T, Kodo H, Quality Control for New type of Cord Blood/ Cord Bank for HSCT and others, WS-1, AisaCORD 2013, Kobe, Japan. April 2013
  2. Nagamura-Inoue T, He H, and Tojo A. Wharton jelly is a rich source of mesenchymal stem cells Symposium 2-2, AisaCORD 2013, Kobe, Japan. April 2013

Conference presentation

  1. H He,, T Nagamura-Inoue, H Tsunoda, Y Yamamoto, Y Mori, and A Tojo, The Immunosupressive Effect Of Wharton’s Jelly-Derived Mesenchymal Stem Cells in vitro, ASH in Asia, Singapore, Mar. 29, 2014
  2. H He,, T Nagamura-Inoue, H Tsunoda, Y Yamamoto, Y Mori, and A Tojo, The Immunosupressive Effect Of Wharton’s Jelly-Derived Mesenchymal Stem Cells in vitro, 55th ASH annual meeting, New Orleans, Dec. 8, 2013
  3. R. Tanosaki, Y. Okuyama, T. Iseki, M. Handa, S. Kino, T. Kumazawa, S. Yoshida, K. Haraguchi, N. Schimizu, S. Sakai, N. Watanabe, T. Uemura, K. Ikuta, Y. Kawahara, K. Muroi, T. Nagamura-Inoue, M. Takanashi, for the HPC Study Group, the Japan Society of Transfusion Medicine and Cell Therapy (JSTMCT), ASH meeting, New Orleans, Dec. 7, 2013
  4. H. Itonaga, M. Iwanaga, K. Aoki, J. Aoki, K. Ishiyama, T. Kobayashi, T. Sakura, T. Fukuda, T. Yujiri, M. Hirokawa, Y. Morishima, T. Nagamura-Inoue, Y. Atsuta, T. Ishikawa, Y. Miyazaki. Influence of acute and chronic graft-versus-host disease on outcome after allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia, New Orleans, Dec. 7, 2013
  5. Nagamura-Inoue T, Yamamoto Y, Kobayashi S , Yuzawa M, He H, Tsunoda H, and Tojo A. Impact of mTOR inhibitor, Everolimus on inducible regulatory T cells Derived from Cord Blood, International Society of Cellular Therapy (ISCT) Annual meeting, New Zealand, 2013
  6. Tokiko Nagamura-Inoue, Seiichiro Kobayashi, Kazuo Ogami, Yuki Yamamoto, Kiyoko Izawa, and Arinobu Tojo, The Significance of mTOR Inhibitor, Everolimus in TGF-β-Induced Regulatory T cells from Cord Blood., 2180, American Soceity of Hematology Annual meeting, San Diego Convention Center, USA, Dec. 11, 2011
  7. Murata M, Taniguchi S, Nagamura-Inoue T, Kato K, on behalf of the Japan Cord Blood Bank Network. Cord blood transplantation for myelofibrosis: a retrospective analysis from the Japan Cord Blood Bank Network. The 36th annual meeting of the European Group for Blood and Marrow Transplantation, in Vienna, Austria. March 2010
  8. Morio T, Daisuke Tomizawa, Yoshiko Atsuta, Tokiko Nagamura-Inoue, Koji Kato, Tadashi Ariga, Keisei Kawa, Kazutoshi Koike, Hisamichi Tauchi, Michiko Kajiwara, Toshirou, Hara, and Shunichi Kato. Unrelated Umbilical Cord Blood Transplantation for Patients with Primary Immunodeficiency: A Report From the Registry of the Japan Cord Blood Bank Network:, 52nd ASH annual meeting, Orlando, USA, Dec. 6, 2010
  9. S.Kurosawa, K.Yakushijin, T.Yamaguchi, Y. Atsuta, T.Nagamura-Inoue, H.Akiyama, S. Taniguchi, K. Miyamura, S. Takahashi, T. Eto, Y. Morishima, H. Sakamaki and T. Fukuda. Changes In Incidence and Causes of Non-Relapse Mortality (NRM) After Allogeneic Hematopoietic Cell Transplantation (allo-HCT): Are Transplants Improving? 52nd ASH annual meeting, Orlando, USA, Dec. 7, 2010
  10. Ikuo Ishige, Tokiko Nagmaura-Inoue, Masaki J. Honda, Arinobu Tojo, Compatrative study of mesehchymal stem cells derived from arterial, venous, and Wharton’s jelly explants of human umbilical cord., International Society of Cell Therapy, Annual meeting, Philadelphia, 2010
  11. Tokiko Nagamura-Inoue, MD., PhD.1,2, Shunro Kai, MD., PhD.2*, Minoko Takahashi, MD.,PhD.2*, Koji Kato, MD., PhD.2, Keiichi Isoyama, MD., PhD.2*, Masatoshi Jinzen, MD.,PhD.2*, Hiroshi Azuma, MD., PhD.2*, Shuichi Taniguchi, MD., PhD.2, Masao Nakabayashi,MD., PhD.2* and Shunichi Kato, MD., PhD.2*. Unrelated Cord blood transplantation for the patients with CML, a Japan Cord　Blood Bank Network Analysis, Poster session, 48 th ASH meeting, 2006
  12. Tokiko Nagamura-Inoue, MD., PhD.1,7, Hideki Kodo, MD., PhD.2,7*, Tsuneo A. Takahashi,MD., PhD.3,7*, Hideo Mugishima, MD., PhD.4,7, Arinobu Tojo, MD., PhD.1,7 and Shigetaka. Asano, MD., PhD Four cases of donor cell-derived acute myeloid leukemia following unrelated cord blood transplantation for adult patients; Tokyo cord blood bank experiences, Poster session, 48 th ASH meeting
  13. T. Nagamura-Inoue, K. Ogami1, K. Yokoyama, S. Nakayama, I. Ishige, S. Izawa, S. Kobayashi, A. Tojo, LARGE SCALE EX VIVO EXPANSION OF CD4+CD25+FOXP3+ REGULATORY T CELLS FROM PERIPHERAL BLOOD, International Society of Cellular Therapy (ISCT) Annual meeting, Florida, 2008
  14. Tokiko Nagamura-Inoue, MD, PhD, Kazuo Ogami, Kazuaki Yokoyama, Kiyoko Izawa, Seiichiro Kobayashi, Shin Nakayama, Ikuo Ishige, Yusuke Inoue, Jun Ooi, Kaoru Uchimaru, Satoshi Takahashi and Arinobu Tojo, Large Scale Selective Ex Vivo Expansion of CD4+CD25+FOXP3+ Regulatory T Cells from Peripheral Blood, American Society of Hematology, Annual meeting, 2008