AI Article Synopsis
- The study investigates how vascular endothelium affects the movement of hematopoietic stem cells (HSCs) during their transplantation and establishes that it actively encourages their entry into bone marrow niches.
- It reveals that the molecule ROBO4 assists in the translocation of HSCs across blood vessel walls to enter bone marrow, highlighting that the endothelium is not just a barrier but a facilitator for HSC migration into the BM.
- The findings suggest a dual role for vascular endothelium: promoting HSC movement from blood to bone marrow while simultaneously preventing their exit back into the bloodstream, indicating possible new strategies for enhancing hematopoietic therapy.
Article Abstract
Despite the use of hematopoietic stem cells (HSCs) in clinical therapy for over half a century, the mechanisms that regulate HSC trafficking, engraftment, and life-long persistence after transplantation are unclear. Here, we show that the vascular endothelium regulates HSC trafficking into and out of bone marrow (BM) niches. Surprisingly, we found that instead of acting as barriers to cellular entry, vascular endothelial cells, via the guidance molecule ROBO4, actively promote HSC translocation across vessel walls into the BM space. In contrast, we found that the vasculature inhibits the reverse process, as induced vascular permeability led to a rapid increase in HSCs in the blood stream. Thus, the vascular endothelium reinforces HSC localization to BM niches both by promoting HSC extravasation from blood-to-BM and by forming vascular barriers that prevent BM-to-blood escape. Our results uncouple the mechanisms that regulate the directionality of HSC trafficking and show that the vasculature can be targeted to improve hematopoietic transplantation therapies.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325232 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2014.12.013 | DOI Listing |
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