Identification and local manipulation of bone marrow vasculature during intravital imaging

Sci Rep. 2020 Apr 14;10(1):6422. doi: 10.1038/s41598-020-63533-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / diagnostic imaging
  • Arteries / drug effects
  • Arteries / physiology
  • Bone Marrow / blood supply*
  • Bone Marrow / diagnostic imaging*
  • Drug Administration Routes
  • Intravital Microscopy*
  • Leukocyte Common Antigens / metabolism
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Male
  • Mice, Inbred C57BL
  • Norepinephrine / pharmacology
  • Skull / diagnostic imaging
  • Small Molecule Libraries / administration & dosage
  • Transendothelial and Transepithelial Migration / drug effects
  • Vasoconstriction

Substances

  • Small Molecule Libraries
  • Leukocyte Common Antigens
  • Norepinephrine