Biomedical Engineering Reference
In-Depth Information
presented normal hematopoiesis and retained normal numbers of hematopoietic
stem cells in the bone marrow.
Sinusoidal endothelial cells in bone marrow have been revealed as an alternative
hematopoietic stem cells niche called the 'vascular niche. Sinusoids are specialized
vessels that allow cells to extravasate from venous circulation into hematopoietic
tissues. h e vascular niche in adult bone marrow is dei ned as a place for stem cell
mobilization or proliferation and dif erentiation, dif erent from osteoblastic niche,
which is thought to maintain hematopoietic stem cell quiescence over the long
term. Sequential migration of hematopoietic cells, which begins with stem cells
in the osteoblastic niche, progresses through proliferation and dif erentiation and
i nally maturation. In close proximity of the vascular niche, Sugiyama
et al
. (2006)
found that sinusoids are surrounded by reticular cells in bone marrow that express
very high levels of CXCL12 (also known as stroma derived factor 1, SDF-1), a
chemokine required for the maintenance of hematopoietic stem cells. h ey also
demonstrated that both hematopoietic stem cells localized around sinusoids and
hematopoietic stem cells localized to the endosteum or to other locations were
consistently in contact with these CXCL12-expressing reticular cells. h e main
receptor for CXCL12 is CXCR4, which is expressed by hematopoietic stem cells.
CXCL12-CXCR4 signaling is required for the colonization of bone marrow by
hematopoietic stem cells during development and regulates the grat ing of
hematopoietic stem cells at er transplantation.
Migration and homing of hematopoietic stem cells are important physiological
processes in which adhesion molecules, such as sialomucins, selectins and
integrins, play a key role. Migration refers to the leaving of hematopoietic stem cells
from the osteoblastic niche, mobilizing to the vascular niche, entering the blood
vessel through the endothelial cells, and circulating in the vascular system, where
hematopoietic stem cells are in constant contact with endothelial cells. Homing of
hematopoietic stem cells is simply the reverse of this process, with hematopoietic
stem cells leaving circulation to transendothelial migration reaching the vascular
as stem cell factor (SCF), chemokines such as SDF-1 and interleukin 8 (IL-8),
and proteolytic enzymes such as the metalloproteinase (MMP) superfamily
are also involved in migration and homing. Among the membrane-bound
molecules involved in these processes, one of special interest is a sialofucosylated
glycoform of CD44 expressed exclusively on human hematopoietic cells and called
hematopoietic cell E-/L-selectin ligand (HCELL). CD44 is a ubiquitously expressed
glycoprotein that helps cells to adhere to other cells and to matrix proteins, and
participates in the recruitment of certain white blood cells to sites of inl ammation
and in their migration through lymphatic tissues. In hematopoietic stem cells, the
isoforms of CD44 bind to its ligand, hyaluronic acid, which is expressed in the
bone marrow sinusoids and in the endosteal region. On human hematopoietic
