A challenge for long-term human lymphohemopoietic reconstitution in mice with normal immunity

• Project/Area Number: 16590957
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: KIMURA Takafumi Kyoto Prefectural University of Medicine, Hygiene, Assistant Professor, 医学研究科, 助手 (30275193)
• Co-Investigator(Kenkyū-buntansha): SONODA Yoshiaki Kansai Medical University, Hygiene, Professor, 医学部, 教授 (60206688) ; IKEHARA Susumu Kansai Medical University, Pathology, Professor, 医学部, 教授 (90108986) ; KAKAZU Naoki Kyoto Prefectural University of Medicine, Hygiene, Assistant Professor, 医学研究科, 助手 (20264757)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: hematopoietic stem cell / xenotransplantation / flow cytometry

Research Abstract

We transplanted human bone marrow cells into a total of 108 recipient mice with normal immunity (C57BL/6 and BDF-1), aiming at long-term human lymphohemopoietic reconstitution. Unexpectedly, most recipient mice receiving transplants (intra-bone marrow injection) of human marrow cells showed human cell repopulation for more than 18 month. The percentage of human cells in mouse bone marrow was confirmed to be 2 to 5 % by flow cytometric analysis. Moreover, no mice bearing human hemopoietic cells had obvious GvHD reaction, suggesting the usefulness of IBMI for prevention of lethal allogeneic immune responses.
We also found and reported the distinct and profound stem cell property of human CD34-negative (CD34^-) cells as compared with CD34^+ progenitors isolated from human umbilical cord blood using a NOD/SCID mice as recipients.
In addition, we reported impaired stem cell capacity, such as proliferation and differentiation potentials, of human CD34^+ cells isolated by clinical grade-immunomagnetic beads systems.
In the next step, we will try to improve the method for xenotransplants in order to get higher human cell repopulation in mice with normal immunity.

Research Products

• [Journal Article] Identification and hematopoietic potential of CD45^- clonal cells with very immature phenotype (CD45^-CD34^-CD38^-Lin^-)in patients with myelodysplastic syndromes. (2005)
  • Author(s): Ogata K, Satoh C, Tachibana M, Hyodo H, Tamura H, Dan K, Kimura T, Sonoda Y, Tsuji T.
  • Journal Title: Stem Cells 23 Pages: 619-630
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification and hematopoietic potential of CD45^- clonal cells with very immature phenotype (CD45^-CD34^-CD38^-Lin^-) in patients with myelodysplastic syndromes. (2005)
  • Author(s): Ogata K, Satoh C, Tachibana M, Hyodo H, Tamura H, Dan K, Kimura T, Sonoda Y, Tsuji T.
  • Journal Title: Stem Cells 23 Pages: 619-630
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34^+CD38^- cells : possible role of VIP as a growth-promoling factor for hematopoietic stem/ progenitor cells. (2004)
  • Author(s): M, Kimura T, Kishimoto Y, Tatekawa T, Baba Y, Nishizaki T, Matsuzaki N, Taniguchi Y, Yoshihara S, Ikegame K, Shirakata T, Nishida S, Masuda T, Hosen N, Tsuboi A, Oji Y, Oka Y, Ogawa H, Sonoda Y, Sugiyama H, Kawase I, Soma T.
  • Journal Title: Leikemia 18 Pages: 912-921
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The sphingosine 1-phosphate agonist FTY720 supports CXCR4-dependent migration and bone marrow homing of human CD34^+ progenitor cells. (2004)
  • Author(s): Kimura T, Boehmler AM, Seitz G, Kuci S, Wiesner T, Brinkmann V, Kanz L, Mohle R.
  • Journal Title: Blood 103 Pages: 4478-4486
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34^+CD38^-cells : possible role of VIP as a growth- promoting factor for hematopoietic stem/ progenitor cells. (2004)
  • Author(s): Kawakami M, Kimura T, Kishimoto Y, Tatekawa T, Baba Y, Nishizaki T, Matsuzaki N, Taniguchi Y, Yoshihara S, Ikegame K, Shirakata T, Nishida S, Masuda T, Hosen N, Tsuboi A, Oji Y, Oka Y, Ogawa H, Sonoda Y, Sugiyama H, Kawase I, Soma T.
  • Journal Title: Leukemia 18 Pages: 912-921
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The sphingosine 1-phosphate agonist FTY720 supports CXCR4-dependent migration and bone marrow homing of human CD34^+ progenitor cells. (2004)
  • Author(s): Kimura T, Boehmler AM, Seitz G, Kuci S, Wiesner T, Brinkmann V, Kanz L, MOhle R.
  • Journal Title: Blood 103 Pages: 4478-4486
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The sphingosine 1-phosphate agonist FTY720 supports CXCR4-dependent migration and bone marrow homing of human CD34^+ progenitor cells. (2004)
  • Author(s): Kimura T.Boehmler AM, Seitz G, Kuci S, Wiesner T, Brinkmann V, Kanz L, Mohle R.
  • Journal Title: Blood 103 Pages: 4478-4486
• [Journal Article] Proliferative and migratory potentials of human cord blood-derived CD34^- severe combined immunodeficiency repopulating cells that retain secondary reconstituting capacity. (2004)
  • Author(s): Kimura T, Wang J, Matsui K, Imai S, Yokoyama S, Nishikawa M, Ikehara S, Sonoda Y.
  • Journal Title: Int.J.Hematol. 79 Pages: 328-333
  • NAID: 10013081994
• [Journal Article] Impaired stem cell function of CD34^+ cells selected by two different immunomagnetic beads systems. (2004)
  • Author(s): Kimura T, Minamiguchi H, Wang J, kaneko H, Nakagawa H, Fujii H, Sonoda Y.
  • Journal Title: Leukemia 18 Pages: 566-574