Biomedical Engineering Reference
In-Depth Information
Mobilization as a Scienti fi cally Based Novel Approach
to Stroke Therapy
In the studies performed by Shyu and Lee with collaborators (2005 and 2006) on
rats, the mobilization step was used to approach stem cell therapy and functional
recovery of stroke [
18,
19
]. Subcutaneous administration of G-CSF one day after
right middle cerebral artery ligation and consecutive ischemia in rats, in the dosage
of 50 mg/kg/day during 5 days, has improved body asymmetry and locomotor
activity in experimental group of rats compared to control which did not receive
G-CSF [
18
]. The elevated body swing test was used to estimate body asymmetry.
Locomotor activity was assessed in activity chamber. Beside these results in the
same study, the authors have found a decreased infarction volume, determined by
MRI from an average of 176 mm
3
in saline-treated controls (ligation only) to
61 mm
3
in G-CSF-treated animals. BrdU labeling of injected cells used to follow
the engraftment of G-CSF-mobilized hematopoietic stem cells (HSC) has shown
that BrdU immunoreactive cells have been found in the ipsilateral cortex near the
infracted boundary and subventricular region. It is noteworthy to mention that
BrdU immunoreactive cells were also found around the lumen of varying calibers
of blood vessels in the perivascular portion (also on the endothelial cell lining of
the vessel wall). The results of double-staining immunohistochemistry under laser
scanning confocal microscopy have shown some BrdU cells co-localized for
antibodies for Neu-N, MAP-2, GFAP, and VWF in the brain of G-CSF-treated rats,
indicating differentiation of dividing stem cells into their progenitors from HSCs.
The increased expression of CXCR4 was also found in the G-CSF-treated rats in
comparison with contralateral side and control rats, as well as their presence in
cortical and vascular endothelial cells indicating that cerebroendothelial SDF-1
can be a chemoattractant for peripheral blood stem cells. The data were encourag-
ing in terms of further consideration; that disruption of the blood-brain barrier may
facilitate selective entry of HSCs into the ischemic rather than the non-ischemic
contralateral hemisphere. It is suggested by others that in ischemic rat brain a num-
ber of neurotrophic factors are released, which have been shown to result in human
bone marrow stromal cell factor production [
19
] . Therefore, the authors speculated
that ischemic damage to brain tissue may result in the release of trophic factors,
which in turn may target HSCs to damaged tissue. It would be of great importance
to determine which signaling molecules attract HSCs and direct their migration to
damaged areas.
The other study performed by the same authors, quite recently, not using
mobilization but transplantation of PBMCs [
18
] has shown by approach with laser
scanning confocal microscopy that rats receiving intracerebral PBMCs transplanta-
tion were seen to differentiate into glial cells GFAP+, Neu-N + cells, and vWF + positive
cells, thereby enhancing neuroplastic effects in the ischemic brain. In addition,
PBSC implantation promoted the formation of new vessels, thereby increasing the
local cortical blood flow in the alchemic hemispheres. They suggested that involvement
