Microvasculature as a gatekeeper for stem cell homing and mobilization

Publication Type:

Journal Article

Source:

Angiogenesis, Springer, Volume 17, Number 1, p.302–302 (2014)

URL:

http://scholars.fhcrc.org/2892/

Keywords:

2014, Clinical Research Division, February 2014

Abstract:

In this study, we developed a 3D vascular niche that models the cell? cell interactions and spatial properties of the bone marrow to study trafficking of normal and leukemic stem cells through the endothelium into the extravascular niche. To better approximate the marrow microenvironment, two stromal cell lines, HS27a, which expresses stem cell niche-associated proteins, and HS5, which secretes copious amounts of growth factors, are embedded in the matrix. When either normal or leukemic CD34+ cells are perfused through the microvessels, they adhere to the vessel walls, and some penetrate through the endothelium and invade the matrix. The efficiency of the adhesion, penetration, and invasion differs between HS27a and HS5 supplemented matrices, normal and leukemic cells, and with or without monocytes. Normal CD34+ cells adhere and migrate significantly more into the matrix when the vessel is surrounded by either stromal cell line compared to vessels without stroma. Contrastingly, fewer leukemic cells adhere to the vessel, but more migrate compared to normal CD34+ cells regardless of stromal presence. When monocytes were perfused 24 h prior, the CD34+ cells adhered less to the vessel wall but migrated more into the matrix, particularly with HS5; leukemic cells migrated and adhered more only with HS27a. Our preliminary studies lay the foundation for (1) recapitulating a 3D marrow microvascular environment, (2) understanding the functions involved in stem cell homing, and (3) functional differences in normal versus leukemic cell homing. Once defined, this system can be applied to understanding the maintenance of leukemic cells within the marrow and provide a tool for testing novel therapeutic targets for leukemia.