Biomedical Engineering Reference
In-Depth Information
Application of Mesenchymal Stem Cell-Derived
Cardiomyocytes as Bio-pacemakers: Current Status and
Problems to Be Solved
Yuichi Tomita
1,2
, Shinji Makino
1
, Daihiko Hakuno
1,2
, Naoichiro Hattan
1
,
Kensuke Kimura
1
, Shunichiro Miyoshi
2
, Mitsushige Murata
1,2
, Masaki Ieda
1,2
,
and Keiichi Fukuda
1
1
Department of Regenerative Medicine and Advanced Cardiac Therapeutics,
Keio University School of Medicine, Institute of Integrated Medical Research,
35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
kfukuda@sc.itc.keio.ac.jp
2
Cardiology Division, Department of Internal Medicine,
Keio University School of Medicine,
35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan
Abstract.
Bone marrow mesenchymal stem cells (CMG cells) are multipotent and can be in-
duced by 5-azacytidine to differentiate into cardiomyocytes. We characterized the electro-
physiological properties of these cardiomyocytes and investigated their potential for use as
transplantable bio-pacemakers. After differentiation, action potentials in spontaneously beating
cardiomyocytes were initially sinus node-like, but subsequently became ventricular
cardiomyocyte-like. RT-PCR established that ion channels mediating
I
K1
and
I
Kr
were ex-
pressed before differentiation. After differentiation, ion channels underlying
I
Ca,L
and
I
f
were
expressed first, followed by ion channels mediating
I
to
and
I
K,ATP
. Differentiated CMG cells
expressed
ȕ
-adrenergic receptors and increased their beat rate in response to isoproterenol.
CMG cardiomyocytes were purified using GFP fluorescence and transplanted into the free
walls of the left ventricles of mice. The transplanted cardiomyocytes survived and connected to
surrounding recipient cardiomyocytes via intercalated discs. Although further innovation is
required, the present findings provide evidence of the potential for bone marrow-derived car-
diomyocytes to be used as bio-pacemakers.
Keywords:
Pacemaker, Bone marrow, Mesenchymal, stem cell, Cardiomyocyte Transplantation.
1 Introduction
The use of artificial pacemakers for treatment of bradyarrhythmias such as sick sinus
syndrome and atrioventricular block is well established. Although artificial pacemak-
ers are considered excellent for this purpose, some problems remain with battery ex-
change, disconnection of the electrode, and infection of the implanted portion [8].
Moreover, with increasing use of medical imaging, an increasing problem has been
that patients with artificial pacemakers cannot undergo magnetic resonance imaging
and may have significant artifacts on computed tomography [29]. For these reasons,
alternatives to the artificial pacemaker have been long awaited.
