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通过调控骨髓间充质干细胞微环境对内皮祖细胞特性进行β3-肾上腺素能调节。

β3-Adrenergic Regulation of EPC Features Through Manipulation of the Bone Marrow MSC Niche.

作者信息

Vafaei Rana, Nassiri Seyed Mahdi, Siavashi Vahid

机构信息

Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

出版信息

J Cell Biochem. 2017 Dec;118(12):4753-4761. doi: 10.1002/jcb.26143. Epub 2017 Jun 12.

DOI:10.1002/jcb.26143
PMID:28513874
Abstract

Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow, however, biological features of this niche are still not fully understood. Given the interactions of MSCs with endothelial cells in different tissues, bone marrow MSC niche may influence the biological features of endothelial progenitor cells (EPCs). To understand the role of the sympathetic nervous system in regulation of the MSC niche, we examined whether the manipulation of the MSC niche via β3-adrenergic signals will affect EPC features. A selective β3 agonist (BRL37344) or a β3 antagonist (SR59230A) was administered in mice for 2 weeks to determine the potential effects of these regimens on the population of CD133 stem cells in the bone marrow. Then, bone marrow-derived MSCs and EPCs were harvested and expanded from the mice to examine the effect of changes in the MSC niche on EPC features. Improved MSC colony forming potency with increased bone marrow stromal cell-derived factor 1 (SDF-1) (also known as C-X-C motif chemokine 12 [CXCL12]) expression was shown as a result of intensification of the bone marrow adrenergic signals through BRL37344 injection. On the other hand, the blockage of these signals limited the expression level of SDF-1 and resulted in bone marrow enrichment of CD133 cells. Manipulation of the MSC niche and decreased SDF-1 expression via SR59230A injection also prompted EPCs to form more colonies with augmented proliferation and differentiation capacity. Overall, our results indicate that the β3-adrenergic signals regulate the MSC niche, thereby resulting in modulation of EPC biological features. J. Cell. Biochem. 118: 4753-4761, 2017. © 2017 Wiley Periodicals, Inc.

摘要

间充质干细胞(MSCs)存在于骨髓中的特定微环境中,然而,该微环境的生物学特性仍未完全明确。鉴于MSCs与不同组织中的内皮细胞存在相互作用,骨髓间充质干细胞微环境可能会影响内皮祖细胞(EPCs)的生物学特性。为了解交感神经系统在调节间充质干细胞微环境中的作用,我们研究了通过β3 - 肾上腺素能信号操纵间充质干细胞微环境是否会影响内皮祖细胞的特性。在小鼠中给予选择性β3激动剂(BRL37344)或β3拮抗剂(SR59230A)2周,以确定这些给药方案对骨髓中CD133干细胞群体的潜在影响。然后,从小鼠中收获并扩增骨髓来源的间充质干细胞和内皮祖细胞,以研究间充质干细胞微环境的变化对内皮祖细胞特性的影响。通过注射BRL37344增强骨髓肾上腺素能信号,结果显示间充质干细胞集落形成能力提高,同时骨髓基质细胞衍生因子1(SDF - 1,也称为C - X - C基序趋化因子12 [CXCL12])表达增加。另一方面,这些信号的阻断限制了SDF - 1的表达水平,并导致骨髓中CD133细胞富集。通过注射SR59230A操纵间充质干细胞微环境并降低SDF - 1表达,也促使内皮祖细胞形成更多集落,其增殖和分化能力增强。总体而言,我们的结果表明β3 - 肾上腺素能信号调节间充质干细胞微环境,从而导致内皮祖细胞生物学特性的调节。《细胞生物化学杂志》118: 4753 - 4761, 2017。© 2017威利期刊公司

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