Biomedical Engineering Reference
In-Depth Information
mechanisms, paracrine effects are most likely to account for the observed effects of
CBSC treatment. It is possible that CBSCs may release nourishing substances that
rally primitive cells within the heart itself to form new blood vessels and muscle.
Transplantation of hESCs
hESCs have been cultured and the hESC-derived cardiomyocytes display structural
and functional properties of early stage cardiomyocytes. This unique differentiation
system may have significant impact on the study of early human cardiac differentia-
tion, functional genomics, pharmacological testing, cell therapy, and tissue engi-
neering. It seems likely that if placed in an adult human heart, these cells would
produce heart muscle cells.
Geron Corporation's scientists and collaborators have demonstrated that hESC-
derived cardiomyocytes, when injected directly into myocardial infarction zone in
rats, improve cardiac structure and contractile function as shown by echocardiogra-
phy and MRI (LaFlamme et al.
2007
). This is the first study to document the poten-
tial clinical utility of regenerating damaged heart muscle by injecting hESC-derived
cardiomyocytes directly into the site of the infarct. In addition, the research con-
firms the effectiveness of a scalable production system that enables Geron to manu-
facture the cardiomyocytes for use in ongoing large animal studies and, ultimately,
testing in humans. To enable survival in the heart, the hESC-derived cardiomyo-
cytes were suspended in a cocktail of survival factors that had been experimentally
determined to dramatically enhance cell survival after injection into the infarcted
ventricular wall. Four weeks later, tissue sections from the infarcted hearts were
examined for the presence of the human cells. The vast majority of human cardio-
myocytes were localized in the central region of the infarct, suggesting that the cells
were capable of engraftment in the hostile environment of the infarct zone.
Moreover, a portion of the cardiomyocytes was mitotic after injection, possibly
enhancing their regenerative efficiency. The grafts also induced a brisk, host-
derived angiogenic response: all the implants contained numerous capillaries lined
with rat endothelial cells.
Transplantation of HSCs
Stem cells can sense injury to a distant organ and migrate to the site of damage to
undergo cell differentiation to promote structural and functional repair. This high
degree of stem cell plasticity led to studies to test whether dead myocardium follow-
ing infarction in mice could be restored by transplanting bone marrow cells (BMCs).
Results of these studies indicate that locally delivered bone marrow cells can generate
de novo myocardium, ameliorating the outcome of coronary artery disease.
Highly enriched HSCs, the so-called side population (SP) cells, were trans-
planted into lethally irradiated mice subsequently rendered ischemic by coronary
artery occlusion for 60 min followed by reperfusion (Jackson et al.
2001
). The
engrafted SP or their progeny migrated into ischemic cardiac muscle and blood
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