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严重联合免疫缺陷小鼠作为人类脐带血造血的体内模型。

SCID mice as an in vivo model of human cord blood hematopoiesis.

作者信息

Vormoor J, Lapidot T, Pflumio F, Risdon G, Patterson B, Broxmeyer H E, Dick J E

机构信息

Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.

出版信息

Blood Cells. 1994;20(2-3):316-20; discussion 320-2.

PMID:7538337
Abstract

Cord blood is increasingly used as an alternative stem cell source for autologous and allogeneic transplantation, particularly in pediatric patients. We therefore adopted our protocol for transplanting human adult bone marrow cells into severe combined immunodeficient (SCID) mice [1] to develop an in vivo model for cord blood hematopoiesis. Intravenous injection of unfractionated or Ficoll-separated cord blood cells into sublethally irradiated SCID mice led to high levels of human hematopoiesis in the majority of the recipients [2]. Multilineage human hematopoiesis including committed and multipotential myeloerythroid progenitors as well as CD19+ B-lymphoid cells were observed in the murine bone marrow for at least 18 weeks. Together, these data indicate that the SCID mice were engrafted with an immature cell that was able to maintain multiple progenitor lineages in vivo. In contrast to our experiences with adult bone marrow, high levels of human cell engraftment in the mouse could be achieved without exogenous cytokine treatment, suggesting that the cord blood cells respond differently to the murine microenvironment. Alternatively, the cord blood cells might have been able to provide themselves with the necessary growth factors in a paracrine fashion. This model will be useful in gaining new insights into the biology of immature human cord blood progenitors and cord blood transplantation.

摘要

脐血越来越多地被用作自体和异体移植的替代干细胞来源,尤其是在儿科患者中。因此,我们采用了将人类成人骨髓细胞移植到严重联合免疫缺陷(SCID)小鼠体内的方案[1],以建立一个脐血造血的体内模型。将未分级或经Ficoll分离的脐血细胞静脉注射到亚致死剂量照射的SCID小鼠体内,导致大多数受体中出现高水平的人类造血现象[2]。在小鼠骨髓中观察到多谱系人类造血,包括定向和多能髓系红系祖细胞以及CD-19+B淋巴细胞,持续至少18周。总之,这些数据表明SCID小鼠植入了一种能够在体内维持多个祖细胞谱系的未成熟细胞。与我们在成人骨髓方面的经验不同,无需外源性细胞因子治疗就能在小鼠体内实现高水平的人类细胞植入,这表明脐血细胞对小鼠微环境的反应不同。或者,脐血细胞可能能够以旁分泌方式为自身提供必要的生长因子。该模型将有助于深入了解未成熟人类脐血祖细胞的生物学特性和脐血移植。

相似文献

1
SCID mice as an in vivo model of human cord blood hematopoiesis.严重联合免疫缺陷小鼠作为人类脐带血造血的体内模型。
Blood Cells. 1994;20(2-3):316-20; discussion 320-2.
2
Multilineage engraftment in NOD/LtSz-scid/scid mice from mobilized human CD34+ peripheral blood progenitor cells.动员的人CD34 +外周血祖细胞在NOD/LtSz-scid/scid小鼠中的多谱系植入。
Biol Blood Marrow Transplant. 1997 Nov;3(5):236-46.
3
Engraftment of ex vivo expanded and cycling human cord blood hematopoietic progenitor cells in SCID mice.体外扩增并处于增殖状态的人脐血造血祖细胞在重症联合免疫缺陷小鼠中的植入。
Exp Hematol. 1998 Jun;26(6):507-14.
4
Cytokine treatment or accessory cells are required to initiate engraftment of purified primitive human hematopoietic cells transplanted at limiting doses into NOD/SCID mice.细胞因子治疗或辅助细胞是启动将以极限剂量移植的纯化原始人类造血细胞植入NOD/SCID小鼠所必需的。
Bone Marrow Transplant. 1999 Feb;23(3):203-9. doi: 10.1038/sj.bmt.1701564.
5
Immature human cord blood progenitors engraft and proliferate to high levels in severe combined immunodeficient mice.未成熟的人类脐血祖细胞在严重联合免疫缺陷小鼠体内植入并大量增殖。
Blood. 1994 May 1;83(9):2489-97.
6
Cytokine-dependent ex vivo expansion of early subsets of CD34+ cord blood myeloid progenitors is enhanced by cord blood plasma, but expansion of the more mature subsets of progenitors is favored.脐带血血浆可增强细胞因子依赖的CD34+脐血髓系祖细胞早期亚群的体外扩增,但更有利于祖细胞较成熟亚群的扩增。
Blood Cells. 1994;20(2-3):436-54.
7
Enhanced engraftment of umbilical cord blood-derived stem cells in NOD/SCID mice by cotransplantation of a second unrelated cord blood unit.通过共移植第二个无关脐带血单位增强脐带血来源干细胞在NOD/SCID小鼠中的植入。
Exp Hematol. 2005 Oct;33(10):1249-56. doi: 10.1016/j.exphem.2005.06.019.
8
Cobblestone area-forming cells, long-term culture-initiating cells and NOD/SCID repopulating cells in human neonatal blood: a comparison with umbilical cord blood.人类新生儿血液中的鹅卵石区域形成细胞、长期培养起始细胞和NOD/SCID重建造血细胞:与脐带血的比较
Bone Marrow Transplant. 2002 Nov;30(9):557-64. doi: 10.1038/sj.bmt.1703714.
9
Enhanced engraftment of human cells in RAG2/gammac double-knockout mice after treatment with CL2MDP liposomes.用CL2MDP脂质体处理后,人细胞在RAG2/γc双敲除小鼠中的植入增强。
Exp Hematol. 2004 Nov;32(11):1118-25. doi: 10.1016/j.exphem.2004.08.002.
10
Improved engraftment of human cord blood stem cells in NOD/LtSz-scid/scid mice after irradiation or multiple-day injections into unirradiated recipients.在对NOD/LtSz-scid/scid小鼠进行辐照后,或将人脐带血干细胞多日注射到未辐照的受体小鼠体内后,人脐带血干细胞在这些小鼠体内的植入情况得到改善。
Biol Blood Marrow Transplant. 1996 Feb;2(1):15-23.

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Curr Opin Virol. 2016 Aug;19:56-64. doi: 10.1016/j.coviro.2016.06.010. Epub 2016 Jul 19.
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Anemia. 2012;2012:265790. doi: 10.1155/2012/265790. Epub 2012 May 23.
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Prevalence of epithelial ovarian cancer stem cells correlates with recurrence in early-stage ovarian cancer.上皮性卵巢癌干细胞的流行率与早期卵巢癌的复发相关。
J Oncol. 2011;2011:620523. doi: 10.1155/2011/620523. Epub 2011 Aug 29.
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Achieving stable human stem cell engraftment and survival in the CNS: is the future of regenerative medicine immunodeficient?在中枢神经系统中实现稳定的人干细胞植入和存活:再生医学的未来是否需要免疫缺陷?
Regen Med. 2011 May;6(3):367-406. doi: 10.2217/rme.11.22.
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Bioluminescent imaging demonstrates that transplanted human embryonic stem cell-derived CD34(+) cells preferentially develop into endothelial cells.生物发光成像显示,移植的人胚胎干细胞源性 CD34(+)细胞优先分化为内皮细胞。
Stem Cells. 2009 Nov;27(11):2675-85. doi: 10.1002/stem.204.
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