Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo.
Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo.
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DOI：
10.1371/journal.pone.0000416
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发表时间：
2007-05-02
期刊：
影响因子：
3.7
通讯作者：
Prockop DJ
中科院分区：
文献类型：
--
作者：
Hung SC;Pochampally RR;Hsu SC;Sanchez C;Chen SC;Spees J;Prockop DJ
干细胞/祖细胞迁移和植入宿主组织的能力是它们在基因和细胞治疗中潜在应用的关键。在感兴趣的细胞中有来自骨髓的贴壁细胞，称为间充质干细胞或多能基质细胞（MSC）。由于骨髓环境缺氧，氧张力范围为1%至7%，我们决定测试缺氧是否可以上调趋化因子受体并增强人骨髓间充质干细胞在体内的移植能力。短期暴露于1%氧的MSCs中，趋化因子受体cx3cr1和CXCR4的mRNA和蛋白表达均增加。低氧暴露1天后，MSCs对fractalkine和SDF-1α的体外迁移呈剂量依赖性。趋化因子受体的阻断抗体显著降低了迁移。异型移植到早期鸡胚胎表明，低氧培养的细胞比常氧培养的细胞更有效地移植，并在宿主组织中产生多种细胞类型。结果表明，在低氧条件下短期培养MSCs可能提供一种促进其在体内植入多种组织的通用方法。
The ability of stem/progenitor cells to migrate and engraft into host tissues is key to their potential use in gene and cell therapy. Among the cells of interest are the adherent cells from bone marrow, referred to as mesenchymal stem cells or multipotent stromal cells (MSC). Since the bone marrow environment is hypoxic, with oxygen tensions ranging from 1% to 7%, we decided to test whether hypoxia can upregulate chemokine receptors and enhance the ability of human MSCs to engraft in vivo. Short-term exposure of MSCs to 1% oxygen increased expression of the chemokine receptors CX3CR1and CXCR4, both as mRNA and as protein. After 1-day exposure to low oxygen, MSCs increased in vitro migration in response to the fractalkine and SDF-1α in a dose dependent manner. Blocking antibodies for the chemokine receptors significantly decreased the migration. Xenotypic grafting into early chick embryos demonstrated cells from hypoxic cultures engrafted more efficiently than cells from normoxic cultures and generated a variety of cell types in host tissues. The results suggest that short-term culture of MSCs under hypoxic conditions may provide a general method of enhancing their engraftment in vivo into a variety of tissues.
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通过缺氧对趋化因子受体CXCR4的调节。
DOI：
10.1084/jem.20030267
发表时间：
2003-11-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.2
作者：
Guo, Y;Hangoc, G;Broxmeyer, HE
通讯作者：
Broxmeyer, HE
影响因子：
2.8
作者：
Chou, SH;Kuo, TK;Lee, OK
通讯作者：
Lee, OK
DOI：
10.1073/pnas.0501029102
发表时间：
2005-04-05
影响因子：
11.1
作者：
Sigurjonsson, OE;Perreault, MC;Glover, JC
通讯作者：
Glover, JC
影响因子：
5.2
作者：
Ji, JF;He, BP;Tay, SSW
通讯作者：
Tay, SSW