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Haematologica. 2020 Jan 23. pii: haematol.2018.196329. doi: 10.3324/haematol.2018.196329. [Epub ahead of print]

Hematopoietic stem and progenitor cells use podosomes to transcellularly cross the bone marrow endothelium.

Author information

1
Sanquin Research & Landsteiner Laboratory, Academic Medical Center, Amsterdam, the Netherlands.
2
Dept. Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
3
Dept for Molecular Biomedicine, Center of Research & Advanced Studies, Mexico-City, Mexico.
4
Max Planck Institute for Molecular Biomedicine, Münster, Germany.
5
Dept. of Medical Biochemistry, Academic Medical Center, Amsterdam, the Netherlands.
6
Sanquin Research & Landsteiner Laboratory, Academic Medical Center, Amsterdam, the Netherlands; j.vanbuul@sanquin.nl.

Abstract

Bone marrow endothelium plays an important role in the homing of hematopoietic stem and progenitor cells upon transplantation, but surprisingly little is known on how the bone marrow endothelial cells regulate local permeability and hematopoietic stem and progenitor cells transmigration. We show that temporal loss of vascular endothelial-cadherin function promotes vascular permeability in BM, even upon low-dose irradiation. Loss of vascular endothelial-cadherin function also enhances homing of transplanted hematopoietic stem and progenitor cells to the bone marrow of irradiated mice although engraftment is not increased. Intriguingly, stabilizing junctional vascular endothelial-cadherin in vivo reduced bone marrow permeability, but did not prevent hematopoietic stem and progenitor cells migration into the bone marrow, suggesting that hematopoietic stem and progenitor cells use the transcellular migration route to enter the bone marrow. Indeed, using an in vitro migration assay, we show that human hematopoietic stem and progenitor cells predominantly cross bone marrow endothelium in a transcellular manner in homeostasis by inducing podosome-like structures. Taken together, vascular endothelial-cadherin is crucial for BM vascular homeostasis but dispensable for the homing of hematopoietic stem and progenitor cells. These findings are important in the development of potential therapeutic targets to improve hematopoietic stem and progenitor cell homing strategies.

KEYWORDS:

Hematopoietic Stem Cell; Homing; Permeability; Stem Cell Transplantation; VE-cadherin

PMID:
31974199
DOI:
10.3324/haematol.2018.196329
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