Biomedical Engineering Reference
In-Depth Information
HSCs in the bone marrow niche
- hypoxic conditions within bone marrow - (mouse)
0,01%O
2
osteoblast
CD45+
4%O
2
Courtesy of Dr M. Kovacevic
Filipovic, PhD Thesis, University of
Belgrade, 2005
endothelial
cells
Fig. 15.1
HSCs in the bone marrow niche—hypoxic conditions within bone marrow (mouse).
Courtesy of Dr. M. Kovacevic Filipovic, Ph.D. Thesis, University of Belgrade, 2005
signaling proteins (SDF-1) that helps guide stem cells to damaged heart tissue [
13
] .
Unfortunately, after an MI, this gene is expressed for less than a week, and the hom-
ing signal it creates quickly fades. In his preclinical studies, Penn has found a way
to turn this homing signal back on. As described in his later publication, he takes
myoblasts from leg muscle, genetically engineers them to overexpress this homing
protein, and then cultures those cells for 4 weeks until he has millions of them. Eight
weeks after heart attack, those engineered cells are re-injected in controlled dosage
with or without injections of the mobilizing agent, growth factor, granulocyte col-
ony stimulating factor (G-CSF). Animals receiving such a treatment showed
significant improvement in cardiac function (up to 90%) as well as neovasculariza-
tion in the infarct zone. Besides SDF-1, Penn et al. have recently identified two
other families of genes that seem to play a role in creating the homing signal of
damaged myocardial tissue. Preclinical studies of these new gene candidates lie
ahead. By better understanding how stem cells get recruited into the blood and
directed towards damaged heart tissue, the researchers are beginning to find a way
to extend the therapeutic window following MI, and more fully restore normal ven-
tricular function.
As we already mentioned, within the bone marrow cavity, stem cells are usually
found in the outer layer close to the inner surface of the bone (the space known as
bone marrow niche, with a low oxygen supply). Since the process of remodeling
bone takes place in the adjacent bone tissue and because studies by
Scadden's
group
and others [
23,
44,
45
] have shown that bone-forming osteoblast cells are essential
