Distinct bone marrow blood vessels differentially regulate haematopoiesis
Tomer Itkin1, Shiri Gur-Cohen1, Joel A Spencer2,3
1Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Nature
|April 14, 2016
Summary
Distinct bone marrow blood vessels regulate stem cell maintenance and immune cell trafficking. Arterial vessels protect stem cells, while permeable sinusoids facilitate immune cell movement and stem cell activation.
Area of Science:
- Hematology
- Vascular Biology
- Stem Cell Biology
Background:
- Bone marrow endothelial cells (BMECs) manage leukocyte trafficking and hematopoietic stem and progenitor cell (HSPC) maintenance.
- The specific mechanisms and vascular locations balancing these BMEC functions remain unclear.
Purpose of the Study:
- To investigate how distinct blood vessel types in the bone marrow differentially regulate HSPC maintenance and leukocyte trafficking.
- To determine if these processes occur at the same vascular sites.
Main Methods:
- Comparative analysis of distinct bone marrow blood vessel types.
- Assessment of vascular permeability and its effect on HSPCs and leukocyte trafficking.
- Evaluation of reactive oxygen species (ROS) levels in HSPCs.
Main Results:
- Less permeable arterial blood vessels maintain hematopoietic stem cells (HSCs) in a low reactive oxygen species (ROS) state.
- Highly permeable sinusoids promote HSPC activation and are the primary sites for leukocyte trafficking.
- Increased plasma exposure in sinusoids elevates HSPC ROS, enhancing migration and differentiation but impairing long-term survival and repopulation.
Conclusions:
- Bone marrow stem cell maintenance and leukocyte trafficking are governed by distinct vascular niches with differing permeability.
- Vascular permeability significantly influences HSPC function, with implications for stem cell transplantation and mobilization strategies.
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