Megakaryocytes co-localise with hemopoietic stem cells and release cytokines that up-regulate stem cell proliferation
Megakaryocytes co-localise with hemopoietic stem cells and release cytokines that up-regulate stem cell proliferation
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DOI：
10.1016/j.scr.2013.05.007
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发表时间：
2013-09-01
影响因子：
1.2
通讯作者：
Nilsson, Susan K.
中科院分区：
文献类型：
--
作者：
Heazlewood, Shen Y.;Neaves, Rebecca J.;Nilsson, Susan K.
我们报告移植的造血干细胞（FISC）优先寄宿在两个细胞的成熟巨核细胞（MM）。两个群体均包含约0.2%的骨髓细胞，这强烈表明了关键的功能相互作用。从骨内膜分离的HSC（eLSKSLAM）表现出显着增加的造血细胞增殖，而在与MM共培养。此外，eLSKSLAM后代保留HSC的潜力，保持长期的多谱系重建能力，在致死性消融受体。造血细胞增殖的增加不是MM接触依赖性的，并且可以用补充有MM条件培养基中鉴定的两种因子的培养基来概括：胰岛素样生长因子结合蛋白-3-（IGFBP-3）和胰岛素样生长因子-1（IGF-1）。我们证明FISC表达IGF-1受体，IGF-1/IGFBP-3诱导的造血细胞增殖增加可被抗IGF-1中和抗体阻断。然而，8 N、16 N或32 N MM与eLSKSLAM的共培养显示，单个倍性的MM没有显著增加造血细胞增殖。我们的数据表明，MM是HSC生态位的重要组成部分，并通过细胞因子释放调节造血细胞增殖。皇冠版权所有（C）2013由爱思唯尔B. V.出版保留所有权利。
We report transplanted hemopoietic stem cells (FISC) preferentially lodge within two cells of mature megakaryocytes (MM). With both populations comprising similar to 0.2% of bone marrow cells, this strongly suggests a key functional interaction. HSC isolated from the endosteum (eLSKSLAM) showed significantly increased hemopoietic cell proliferation while in co-culture with MM. Furthermore, eLSKSLAM progeny retained HSC potential, maintaining long-term multi-lineage reconstitution capacity in lethally ablated recipients. Increased hemopoietic cell proliferation was not MM contact dependent and could be recapitulated with media supplemented with two factors identified in MM-conditioned media: insulin-like growth factor binding protein-3-(IGFBP-3) and insulin-like growth factor-1 (IGF-1). We demonstrate that FISC express the receptor for IGF-1 and that IGF-1/IGFBP-3 induced increased hemopoietic cell proliferation can be blocked by an anti-IGF-1 neutralising antibody. However, co-cultures of 8N, 16N or 32N MM with eLSKSLAM showed that MM of individual ploidy did not significantly increase hemopoietic cell proliferation. Our data suggests that MM are an important component of the HSC niche and regulate hemopoietic cell proliferation through cytokine release. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.