Cell Therapy for Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 169

streptavidin and then bound to biotinylated self-assembling peptides. This biotin
sandwich strategy enabled binding of IGF-1 but did not prevent self-assembly of the
peptides into nanofibers within the myocardium. IGF-1 that was bound to peptide
nanofibers activated Akt, decreased activation of caspase-3, and increased expression
of cardiac troponin I in cardiomyocytes. In studies on rats, cell therapy with IGF-1
delivery by biotinylated nanofibers improved systolic function after experimental MI,
demonstrating how engineering the local cellular microenvironment can improve
cell therapy.
Noninvasive Delivery of Cells to the Heart
by Morph ® guide Catheter
Most methods of delivery of cells to the myocardium are invasive. Morph ® guide
catheter (Biocardia) is a FDA-approved noninvasive device, which is inserted like
a standard angioplasty catheter through a blood vessel in the groin, but instead of
advancing to the coronary artery, the catheter is advanced into the ventricle of the
heart so that it can deliver directly into the heart muscle using a small helical needle.
Twenty patients have been treated to date with this system delivering bone marrow-
derived cells through BioCardia's Investigational Helical Infusion System with
excellent safety results and an average total procedure time from insertion to
removal of catheters of only 43 min. This method of delivery is currently in use at
the University of Miami in a clinical trial on heart failure patients comparing two
cell populations: autologous adult bone marrow derived mononuclear cells and
adult autologous MSCs. These cell populations have excellent safety profiles in
clinical studies performed to date. As cells are taken from the patient's own bone
marrow, there will be no issues of rejection of the cells as foreign by the patient's
immune system.
Cell Therapy for Cardiac Revascularization
Transplantation of Cardiac Progenitor Cells
for Revascularization of Myocardium
Cell transplantation for revascularization has been explored as an alternative to
bypass surgery for severe coronary atherosclerosis. According to one report, c-kit-
positive CPCs activated with IGF-1 and HGF before their injection in proximity of
the site of occlusion of the left coronary artery in rats, engrafted within the host
myocardium forming temporary niches (Tillmanns et al. 2008 ). Subsequently, CPCs
divided and differentiated into endothelial cells and smooth muscle cells and, to a
lesser extent, into cardiomyocytes. The acquisition of vascular lineages appeared to
be mediated by the upregulation of HIF 1a, which promoted the synthesis and