Cell Therapy for Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 196

Role of Cell Therapy in Cardiac Arrhythmias
Cardiac arrhythmias are a leading cause of morbidity in the Western hemisphere.
The risk of developing malignant ventricular tachyarrhythmias is associated with
the extent of myocardial injury and is believed to be the primary cause of approxi-
mately 50% of all cardiovascular deaths. Bradycardia and heart block, which can
result from the normal aging process, further add to the morbidity associated with
cardiac arrhythmias. About 3 million people worldwide carry implanted electrome-
chanical pacemakers, and each year about 600,000 pacemakers are implanted.
Conventional medical therapy is predominantly palliative treatment and com-
monly fails to impede and prevent the morbidity and mortality associated with
cardiac arrhythmias. Radiofrequency catheter ablation of ischemic ventricular
tachycardias is considered adjuvant therapy rather than curative. The implantation
of defibrillators and pacemakers, while generally effective, do have problems which
include: (1) implantation of a electromechanical device and its need for replace-
ment every 4-7 years, (2) surgical and mechanical complications resulting from the
implantation of the device, (3) negative physical and psychological effects of an
implanted mechanical device, (4) a prevalent need to use concurrent antiarrhythmic
therapy and/or radiofrequency modulation/ablation, and (5) a relatively high cost.
Therefore, there is a need to develop alternative therapies for treatment of conduc-
tion abnormalities that overcomes the negative aspects of current treatment methods.
Electrophysiological studies of pluripotent ESCs show that they functionally
express several specialized ion channels indicating potential applications in rhythm
disturbances of the heart. Genetically engineered cell grafts, transfected to express
potassium channels, can couple with host cardiomyocytes and alter the local myo-
cardial electrophysiological properties by reducing cardiac automaticity and pro-
longing refractoriness (Yankelson et al. 2008 ).
Atrioventricular Conduction Block
Cardiomyocytes, developed from hESCs in vitro, can act as biological pacemakers
and restore myocardial mechanical function when transplanted into the pacemaker
region of pig hearts with a slow heart rate due to atrioventricular conduction block
(Kehat et al. 2004 ). Long-term electromechanical integration between host and
donor tissues occurred at several levels. This proof-of-concept study suggests the
use of excitable cell grafts as a biological alternative to implantable pacemaker
devices. The technique could also be used to repair cardiac muscle tissue damaged
during myocardial infarction. It remains to be proven that a biological pacemaker
will function nonstop for years in a sick heart and would not be rejected by the
recipient's immune system.
Electronic pacemakers, currently used for cardiac arrhythmias, cannot react the
way the heart's own pacemaker normally does, for example, raising the heart rate
in response to physical exertion. Efforts are being made to restore the heart's ability