Identification and local manipulation of bone marrow vasculature during intravital imaging
Identification and local manipulation of bone marrow vasculature during intravital imaging
复制标题
活体成像过程中骨髓脉管系统的识别和局部操作
DOI：
10.1038/s41598-020-63533-3
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发表时间：
2020
影响因子：
4.6
通讯作者：
Takubo Keiyo
中科院分区：
文献类型：
--
作者：
Morikawa Takayuki;Tamaki Shinpei;Fujita Shinya;Suematsu Makoto;Takubo Keiyo
骨髓中血流的生理调节对于维持氧和葡萄糖供应以及造血干细胞（HSC）生态位的生理缺氧状态是重要的。然而，骨髓微循环的调控机制尚不清楚。在这里，我们确定了在骨髓中控制血流的血管功能，并评估其收缩性。为了评价Alexa Fluor 633（AF 633;一种动脉标记物）阳性血管的收缩潜力，我们对α-平滑肌肌动蛋白（α-SMA）进行了免疫组织化学，发现其在股骨和颅骨骨髓中的AF 633+血管周围表达。为了验证AF 633+血管收缩性，我们开发了一种简单的系统来局部施用通过经头皮血管渗透BM的血管活性剂。暴露于FITC-葡聚糖（70 kDa）的颅骨表面后，颅骨骨髓中的FITC强度逐渐增加。当我们评估经头皮给予（TCA）去甲肾上腺素（NE）对AF 633+动脉的血管张力和移植血细胞的行为的影响时，NE给予降低了动脉直径和移植细胞的跨内皮迁移，表明肾上腺素能信号传导通过对BMarteries的影响调节HSC微循环和血细胞迁移到BM中。我们的结论是，TCA是一个有用的工具，骨髓研究。
Physiological regulation of blood flow in bone marrow is important to maintain oxygen and glucose supplies but also the physiological hypoxic state of the hematopoietic stem cell (HSC) niche. However, regulatory mechanisms underlying microcirculation in the bone marrow (BM) niche remain unclear. Here, we identify vessels functioning in control of blood flow in bone marrow and assess their contractility. To evaluate contractile potential of Alexa Fluor 633 (AF633; an arterial marker)-positive vessels, we performed immunohistochemistry for α-smooth muscle actin (α-SMA) and found it expressed around AF633+vessels in the femoral and calvarial marrow. To validate AF633+vessel contractility, we developed a simple system to locally administer vasoactive agents that penetrate BM through transcalvarial vessels. After exposure of the calvarial surface to FITC-dextran (70 kDa), FITC intensity in calvarial bone marrow gradually increased. When we evaluated the effect of transcalvarial administration (TCA) of norepinephrine (NE) on vascular tone of AF633+arteries and behavior of transplanted blood cells, NE administration decreased artery diameter and transendothelial migration of transplanted cells, suggesting that adrenergic signaling regulates the HSC niche microcirculation and blood cell migration into the BM via effects on BMarteries. We conclude that TCA is a useful tool for bone marrow research.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Kusumbe, Anjali P.;Ramasamy, Saravana K.;Itkin, Tomer;Mae, Maarja Andaloussi;Langen, Urs H.;Betsholtz, Christer;Lapidot, Tsvee;Adams, Ralf H.
通讯作者：
Adams, Ralf H.
影响因子：
23.9
作者：
Takubo, Keiyo;Goda, Nobuhito;Suda, Toshio
通讯作者：
Suda, Toshio
影响因子：
8.8
作者：
Bixel MG;Kusumbe AP;Ramasamy SK;Sivaraj KK;Butz S;Vestweber D;Adams RH
通讯作者：
Adams RH