Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 28

express cytokines such as chemokine CXCL12, 15 like osteoblasts, and adhesion
molecules for HSC mobilization, homing, 16 and lodging in endosteal bone marrow
HSC niches [ 56 ]. SLAMF1

hematopoietic stem cells close to sinusoids may
monitor the concentration of blood elements.
Hematopoietic stem cell niches regulate the stem cell maintenance in cooperation
with endosteal cells (osteoblasts and osteoclasts) at the interface between bone
and bone marrow, as well as vascular and perivascular cells around bone marrow
sinusoids. The specific microenvironment promotes stem cell survival and self-
renewal and regulates cell differentiation and migration according to the body's
need. Endosteal, vascular, and perivascular cells cooperate and contribute to the
HSC maintenance, expansion, and location. Homeostasis of hematopoietic stem
cells requires many factors (Table 2.2 )[ 57 ].
Many plasmalemmal receptors control the location of hematopoietic stem cells,
among which the calcium-sensing receptor [ 61 ]. 17

+

Calcium-sensing receptors are

particularly expressed by LSK cells.

2.3.2 Cells of Bone Marrow Niches

+ +

Osteopontin osteoblasts that line the endosteal surface of trabecular

bone, bone marrow sinusoid endothelial cells, CXCL12-secreting stromal cells,
adipocytes, and macrophages constitute functional niches of hematopoietic stem
cells in adult bone marrow.
The adipocyte number is inversely correlated with the hematopoietic activity
in the niche. Density of hematopoietic stem cells and progenitors decays in the
adipocyte-rich bone marrow. Bone marrow adipocytes operate as inhibitors of
hematopoiesis [ 59 ].
On the other hand, in vitro, undifferentiated stromal cells and preadipocytes
support hematopoiesis, as they produce growth factors, such as granulocyte-
macrophage (CSF2) and granulocyte (CSF3) colony-stimulating factor. Moreover,

, N-cadherin

15 Chemokine CXCL12 can induce motility, chemotaxis, and adhesion of cells expressing its
receptor, CXC-chemokine receptor-4, as well as secretion of matrix metalloproteinases and
angiogenic factors, such as vascular endothelial growth factor. Association of CXCL12 and
CXCR4 is required for retention and maintenance of adult hematopoietic stem cells.
16 Homing corresponds to recruitment of circulating hematopoietic stem cells to the bone marrow
vasculature and subsequent extravasation that requires adhesion molecules, such as selectins
and integrins. Small GTPases Rac1 and Rac2 are also implicated in homing and retention of
hematopoietic stem cells in the endosteal bone marrow HSC niches.
17 The endosteal niche for hematopoietic stem cells is characterized by a high Ca 2 + concentration
(more than 20-fold the plasmatic one), due to active bone remodeling in the endosteum by
osteoclasts.