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使用正常供体的动员外周血干细胞进行同种异体移植。

The use of mobilized peripheral blood stem cells from normal donors for allografting.

作者信息

Anderlini P, Körbling M

机构信息

The University of Texas M.D. Anderson Cancer Center, Department of Hematology, Houston 77030, USA.

出版信息

Stem Cells. 1997;15(1):9-17. doi: 10.1002/stem.150009.

DOI:10.1002/stem.150009
PMID:9007218
Abstract

Peripheral blood stem cells (PBSCs) are gaining increasing acceptance as an alternative to bone-marrow (BM)-derived stem cells for allografting. Although scarce under steady-state conditions, CD34+ progenitor cells can be effectively mobilized into the peripheral blood (PB) in the vast majority of normal donors with a brief (3-4 days) course of recombinant human (rHu)G-CSF. Those cytokine-peripheralized progenitor cells and, among them, pluripotent stem cells, are collected by apheresis in sufficient amounts to achieve complete and permanent alloengraftment after myeloablative treatment in patients with primarily malignant hematologic disorders. The short-term tolerability profile of PBSC mobilization and apheresis in normal donors appears to be acceptable, although continued monitoring is necessary to ensure long-term safety. When compared with BM progenitor cells, mobilized PBSCs seem to exhibit a more primitive phenotype and a different clonogenic potential. The impact of factors affecting the efficiency of PBSC mobilization, such as rHuG-CSF dose, duration of cytokine treatment, and, to a lesser extent, donor age is now being recognized. Potential ways to optimize and possibly "engineer" PBSC collection, such as the use of cytokine/chemokine combinations (e.g., thrombopoietin, stem cell factor, etc.) and monoclonal antibodies directed against integrin receptors on CD34+ progenitor cells, are now being explored as well. In the clinical setting, engraftment after PBSC allografting is rapid and probably faster than after BM allografting. PBSC allografting seems to be associated with an incidence and severity of acute graft-versus-host disease (GVHD) comparable to the ones observed after BM allografting, although the incidence of chronic GVHD after allogeneic PBSC transplantation is still controversial. The infusion of a larger number of lymphoid cells appears to translate into a more rapid immunologic recovery and may lead to an enhanced graft-versus-leukemia effect. The collection of large numbers of mobilized PBSCs should provide ample opportunities for graft engineering and gene therapy. PBSCs may eventually replace, at least in part, BM as the preferred source of stem cells for both auto- and allotransplantation.

摘要

外周血干细胞(PBSCs)作为同种异体移植中骨髓(BM)来源干细胞的替代物,正越来越被人们所接受。尽管在稳态条件下数量稀少,但通过短期(3 - 4天)的重组人(rHu)G - CSF治疗,绝大多数正常供体中的CD34 +祖细胞可有效地动员到外周血(PB)中。这些细胞因子外周化的祖细胞,其中包括多能干细胞,通过单采术收集的量足以在原发性恶性血液病患者接受清髓治疗后实现完全和永久性的同种异体植入。正常供体中PBSC动员和单采术的短期耐受性似乎是可以接受的,尽管需要持续监测以确保长期安全性。与BM祖细胞相比,动员的PBSCs似乎表现出更原始的表型和不同的克隆形成潜力。影响PBSC动员效率的因素,如rHuG - CSF剂量、细胞因子治疗持续时间以及在较小程度上的供体年龄,现在已得到认可。目前也在探索优化并可能“设计”PBSC采集的潜在方法,如使用细胞因子/趋化因子组合(如血小板生成素、干细胞因子等)以及针对CD34 +祖细胞上整合素受体的单克隆抗体。在临床环境中,PBSC同种异体移植后的植入迅速,可能比BM同种异体移植后更快。PBSC同种异体移植似乎与急性移植物抗宿主病(GVHD)的发生率和严重程度相当,与BM同种异体移植后观察到的情况相似,尽管异基因PBSC移植后慢性GVHD的发生率仍存在争议。输注大量淋巴细胞似乎能转化为更快的免疫恢复,并可能导致增强的移植物抗白血病效应。收集大量动员的PBSCs应为移植物工程和基因治疗提供充足的机会。PBSCs最终可能至少部分取代BM,成为自体和异体移植中干细胞的首选来源。

相似文献

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The use of mobilized peripheral blood stem cells from normal donors for allografting.使用正常供体的动员外周血干细胞进行同种异体移植。
Stem Cells. 1997;15(1):9-17. doi: 10.1002/stem.150009.
2
[A pilot study of G-CSF mobilized allogeneic bone marrow cells plus peripheral blood stem cells transplantation for malignant hematological diseases].粒细胞集落刺激因子动员的异基因骨髓细胞加外周血干细胞移植治疗恶性血液病的初步研究
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[Collection of hematopoietic progenitor cells from healthy donors].[从健康供体采集造血祖细胞]
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Similar survival following HLA-identical sibling transplantation for standard indication in children with haematologic malignancies: a single center comparison of mobilized peripheral blood stem cell with bone marrow transplantation.血液系统恶性肿瘤儿童标准适应症的 HLA 全相合同胞移植后的相似生存率:动员外周血干细胞移植与骨髓移植的单中心比较
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Peripheral Blood Stem Cells: A Novel Source for Allogeneic Transplantation.外周血干细胞:异基因移植的新来源。
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Peripheral blood progenitor cell transplantation: a replacement for marrow auto- or allografts.外周血祖细胞移植:替代骨髓自体或同种异体移植。
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Rapid engraftment after allogeneic transplantation of density-enriched peripheral blood CD34+ cells in patients with advanced hematologic malignancies.晚期血液系统恶性肿瘤患者接受密度富集外周血CD34+细胞同种异体移植后的快速植入。
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The role of granulocyte colony-stimulating factor in mobilization and transplantation of peripheral blood progenitor and stem cells .粒细胞集落刺激因子在外周血祖细胞和干细胞动员及移植中的作用
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Blood stem cell procurement: donor safety issues.血液干细胞采集:供体安全问题。
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Hematopoietic stem cell transplantation for high-risk adult patients with severe aplastic anemia; reduction of graft failure by enhancing stem cell dose.高危成年重型再生障碍性贫血患者的造血干细胞移植;通过增加干细胞剂量降低移植物失败率。
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引用本文的文献

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Mobilized Multipotent Hematopoietic Progenitors Promote Expansion and Survival of Allogeneic Tregs and Protect Against Graft Versus Host Disease.动员多能造血祖细胞促进同种异体 Tregs 的扩增和存活,并防止移植物抗宿主病。
Front Immunol. 2021 Feb 12;11:607180. doi: 10.3389/fimmu.2020.607180. eCollection 2020.
2
Increased CD83 expression of CD34-positive monocytes in donors during peripheral blood stem cell mobilization in humans.在人类外周血造血干细胞动员期间,供者 CD34+单核细胞中 CD83 的表达增加。
Sci Rep. 2019 Nov 11;9(1):16499. doi: 10.1038/s41598-019-53020-9.
3
Multi-color immune-phenotyping of CD34 subsets reveals unexpected differences between various stem cell sources.
CD34 亚群的多色免疫表型分析揭示了不同干细胞来源之间意想不到的差异。
Bone Marrow Transplant. 2016 Aug;51(8):1093-100. doi: 10.1038/bmt.2016.88. Epub 2016 Apr 4.
4
Future perspectives: should Th17 cells be considered as a possible therapeutic target in acute myeloid leukemia patients receiving allogeneic stem cell transplantation?未来展望:在接受异基因造血干细胞移植的急性髓系白血病患者中,是否应将 Th17 细胞视为可能的治疗靶点?
Cancer Immunol Immunother. 2011 Dec;60(12):1669-81. doi: 10.1007/s00262-011-1118-z. Epub 2011 Oct 12.
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The human-sheep chimeras as a model for human stem cell mobilization and evaluation of hematopoietic grafts' potential.人羊嵌合体作为人类干细胞动员及造血移植物潜力评估的模型。
Exp Hematol. 2007 Oct;35(10):1594-600. doi: 10.1016/j.exphem.2007.07.009.