骨髄破壊的処置相当の放射線照射によるマウス骨髄ストローマ細胞におけるSDF-1 発現低下
臍帯血移植後の生着不全の機構解明のため，骨髄破壊的前処置の一つである放射線照射による骨髄ストローマの造血細胞維持能やホーミング関連因子SDF-1について検討した．マウスストローマ細胞(HESS-5) に10Gy 以上の放射線照射を行うと非照射細胞に比べ，SDF-1やJagged-1 のmRNA 発現が有意に低下し，同時に培養上清中のSDF-1 蛋白濃度も有意に低下した．一方，放射線照射したHESS-5 細胞とヒト臍帯血CD34＋ 細胞との共培養実験では，20 Gy まで線量を増加させても臍帯血CD34＋ 細胞の増幅・維持能は変化しなかった．10Gy 以上の照射を行ったHESS-5 細胞の培養上...
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| Published in | 日大医学雑誌 Vol. 74; no. 2; pp. 50 - 56 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本大学医学会
01.04.2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0029-0424 1884-0779 |
| DOI | 10.4264/numa.74.50 |
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| Abstract | 臍帯血移植後の生着不全の機構解明のため，骨髄破壊的前処置の一つである放射線照射による骨髄ストローマの造血細胞維持能やホーミング関連因子SDF-1について検討した．マウスストローマ細胞(HESS-5) に10Gy 以上の放射線照射を行うと非照射細胞に比べ，SDF-1やJagged-1 のmRNA 発現が有意に低下し，同時に培養上清中のSDF-1 蛋白濃度も有意に低下した．一方，放射線照射したHESS-5 細胞とヒト臍帯血CD34＋ 細胞との共培養実験では，20 Gy まで線量を増加させても臍帯血CD34＋ 細胞の増幅・維持能は変化しなかった．10Gy 以上の照射を行ったHESS-5 細胞の培養上清は，臍帯血単核球の遊走能を有意に低下させた．マウスに10Gy 以上の放射線照射を行うと，マウス骨髄ストローマ分画の生細胞数は，非照射マウスに比べ約1/10 に減少し，SDF-1 の発現も低下していた．骨髄破壊的前処置に相当する線量の放射線照射は骨髄ストローマの細胞数やSDF-1 などの発現を減少させており，移植細胞の骨髄への生着を障害している可能性があることが明らかになった． |
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| AbstractList | 臍帯血移植後の生着不全の機構解明のため，骨髄破壊的前処置の一つである放射線照射による骨髄ストローマの造血細胞維持能やホーミング関連因子SDF-1について検討した．マウスストローマ細胞(HESS-5) に10Gy 以上の放射線照射を行うと非照射細胞に比べ，SDF-1やJagged-1 のmRNA 発現が有意に低下し，同時に培養上清中のSDF-1 蛋白濃度も有意に低下した．一方，放射線照射したHESS-5 細胞とヒト臍帯血CD34＋ 細胞との共培養実験では，20 Gy まで線量を増加させても臍帯血CD34＋ 細胞の増幅・維持能は変化しなかった．10Gy 以上の照射を行ったHESS-5 細胞の培養上清は，臍帯血単核球の遊走能を有意に低下させた．マウスに10Gy 以上の放射線照射を行うと，マウス骨髄ストローマ分画の生細胞数は，非照射マウスに比べ約1/10 に減少し，SDF-1 の発現も低下していた．骨髄破壊的前処置に相当する線量の放射線照射は骨髄ストローマの細胞数やSDF-1 などの発現を減少させており，移植細胞の骨髄への生着を障害している可能性があることが明らかになった． |
| Author | 風間, 美奈子 辻, 孝 高橋, 昌里 石毛, 美夏 松本, 松太郎 麦島, 秀雄 |
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| References | 1) Nagasawa T, Hirota S, Tachibana K, et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 1996;382: 635-638. 10) Piersma AH, Ploemacher RE, Brockbank KG. Radiation damage to femoral hemopoietic stroma measured by implant regeneration and quantitation of fibroblastic progenitors. Exp Hematol 1983; 11: 884-890. 6) Tsuji T, Itoh K, Nishimura-Morita Y, et al. CD34high+ CD38(low/-) cells generated in a xenogenic coculture system are capable of both long-term hematopoiesis and multiple differentiation. Leukemia 1999; 13: 1409-1419. 5) Tsuji T, Ogasawara H, Aoki Y, et al. Characterization of murine stromal cell clones established from bone marrow and spleen. Leukemia 1996; 10: 803-812. 9) Semerad CL, Christopher MJ, Liu F, et al. G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood 2005; 106: 3020-3027. 12) Varnum-Finney B, Xu L, Brashem-Stein C, et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med 2000; 6: 1278-1281. 2) Ara T, Tokoyoda K, Sugiyama T, et al. Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. Immunity 2003; 19: 257-267. 4) Lapidot T, Dar A, Kollet O. How do stem cells find their way home- Blood 2005; 106: 1901-1910. 3) Sugiyama T, Kohara H, Noda M, et al. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 2006; 25: 977-988. 8) Christopherson KW 2nd, Hangoc G, Broxmeyer HE. Cell surface peptidase CD26/dipeptidylpeptidase IV regulates CXCL12/stromal cell-derived factor-1 alpha-mediated chemotaxis of human cord blood CD34+ progenitor cells. J Immunol 2002; 169: 7000-7008. 11) Madhusudhan T, Majumdar SS, Mukhopadhyay A. Degeneration of stroma reduces retention of homed cells in bone marrow of lethally irradiated mice. Stem Cells Dev 2004; 13: 173-182. 7) Kawada H, Ando K, Tsuji T, et al. Rapid ex vivo expansion of human umbilical cord hematopoietic progenitors using a novel culture system. Exp Hematol 1999; 27: 904-915. |
| References_xml | – reference: 9) Semerad CL, Christopher MJ, Liu F, et al. G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood 2005; 106: 3020-3027. – reference: 2) Ara T, Tokoyoda K, Sugiyama T, et al. Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. Immunity 2003; 19: 257-267. – reference: 7) Kawada H, Ando K, Tsuji T, et al. Rapid ex vivo expansion of human umbilical cord hematopoietic progenitors using a novel culture system. Exp Hematol 1999; 27: 904-915. – reference: 4) Lapidot T, Dar A, Kollet O. How do stem cells find their way home- Blood 2005; 106: 1901-1910. – reference: 12) Varnum-Finney B, Xu L, Brashem-Stein C, et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med 2000; 6: 1278-1281. – reference: 1) Nagasawa T, Hirota S, Tachibana K, et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 1996;382: 635-638. – reference: 8) Christopherson KW 2nd, Hangoc G, Broxmeyer HE. Cell surface peptidase CD26/dipeptidylpeptidase IV regulates CXCL12/stromal cell-derived factor-1 alpha-mediated chemotaxis of human cord blood CD34+ progenitor cells. J Immunol 2002; 169: 7000-7008. – reference: 10) Piersma AH, Ploemacher RE, Brockbank KG. Radiation damage to femoral hemopoietic stroma measured by implant regeneration and quantitation of fibroblastic progenitors. Exp Hematol 1983; 11: 884-890. – reference: 3) Sugiyama T, Kohara H, Noda M, et al. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 2006; 25: 977-988. – reference: 5) Tsuji T, Ogasawara H, Aoki Y, et al. Characterization of murine stromal cell clones established from bone marrow and spleen. Leukemia 1996; 10: 803-812. – reference: 11) Madhusudhan T, Majumdar SS, Mukhopadhyay A. Degeneration of stroma reduces retention of homed cells in bone marrow of lethally irradiated mice. Stem Cells Dev 2004; 13: 173-182. – reference: 6) Tsuji T, Itoh K, Nishimura-Morita Y, et al. CD34high+ CD38(low/-) cells generated in a xenogenic coculture system are capable of both long-term hematopoiesis and multiple differentiation. Leukemia 1999; 13: 1409-1419. |
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| SubjectTerms | stromal cell-derived factor-1 生着不全 臍帯血移植 骨髄微小環境 骨髄破壊的前処置 |
| Title | 骨髄破壊的処置相当の放射線照射によるマウス骨髄ストローマ細胞におけるSDF-1 発現低下 |
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