Biomedical Engineering Reference
In-Depth Information
BMSCs is directly correlated with cardiovascular risk and life expectancy. Exercise
and hormones are physiological stimuli for the mobilization of BMSCs, whereas
cardiovascular risk factors severely reduce their number and functions. Current
cardiovascular medications increase the amounts of autologous BMSCs.
AMR001 (Amorcyte Inc) consists of autologous BMSCs isolated from adult bone
marrow using a cytokine gradient. The isolation gradient used by Amorcyte identifies
cells that respond to cytokine signals released as a response to myocardial infarction.
The cells based on this biologic activity sets AMR001 apart from other autologous
treatments in development in two ways; (1) the homogeneity of the cell population
in AMR001 should provide more consistent efficacy than a heterogeneous mixture
of bone marrow-derived cells; (2) cells' response to infarction-specific cytokine sig-
nals enables them to penetrate the peri-infarct zone upon injection into the infarct-
related artery. This is important because often a major limitation in cell therapy is
being able to target and penetrate the damaged area to deliver therapeutics.
The process of harvesting, purifying, and re-administering the cells to the patient
is minimally invasive and can be completed within 24-48 h. Both the harvesting
and the re-administration are performed in a conscious patient under sedation.
AMR001 completed phase I clinical trials in 2009 demonstrating feasibility, safety,
and biologic activity at a threshold dose. This is the first stem cell trial in AMI ever
conducted that has prospectively established a significant relationship between
dose and effect. If successful, AMR001 use will be expanded into chronic ischemia
and congestive heart failure.
Autologous Bone Marrow-Derived Mesenchymal Precursor Stem Cells
Texas Heart Institute is treating heart attack patients with autologous bone marrow-
derived mesenchymal precursor stem cells (MPCs) to promote better healing and
to prevent congestive heart failure. A randomized phase I trial has enrolled 25
patients in three phases in which the patient receives 25, 75, or 150 million MPCs,
which are injected into damaged but still viable areas of the heart muscle. Preclinical
trials have established that 10 days after the heart attack is the optimal time to give
this treatment. The heart is still inflamed in the days just after a heart attack and if
one waits too late to administer MPCs, the heart will develop much scar tissue and
its ability to pump will already be compromised. 3D imaging technology is used to
map the electrical and mechanical function of the left ventricle. The study is spon-
sored by Angioblast Systems, a company which provides the proprietary MPCs.
MPCs can also be administered via a catheter.
Transplantation of Cord Blood Stem Cells
Cord blood-derived stem cells (CBSCs) have been transplanted into the acutely
ischemic lateral wall of the left ventricle (LV) in a porcine model of acute MI
(Ghodsizad et al.
2009
). Transplantation of CBSCs significantly improved LV func-
tion and prevented scar formation as well as LV dilation. Since differentiation,
apoptosis, and macrophage mobilization at infarct site were excluded as underlying
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