Identification and local manipulation of bone marrow vasculature during intravital imaging.

Abstract:

: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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Morikawa T,Tamaki S,Fujita S,Suematsu M,Takubo K

doi

10.1038/s41598-020-63533-3

subject

Has Abstract

pub_date

2020-04-14 00:00:00

pages

6422

issue

1

issn

2045-2322

pii

10.1038/s41598-020-63533-3

journal_volume

10

pub_type

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