Biomedical Engineering Reference
In-Depth Information
angina pectoris through heart rate reduction. Conversely, it may be envisaged that the
availability of ivabradine may be exploited to fine tune the pulse rate when used in
conjunction with HCN-based gene therapy for the creation of a biopacemaker [3, 7].
3.4 Cell Therapy
In addition to these gene therapy strategies, various cell therapy approaches have
yielded remarkable results. Here, we discuss some of these approaches as well as the
genetic modification of applied stem cells.
Fig. 4.
Electrocardiograms of leads I, II, RA and LA (overlying injection site). The initial two
beats represent normal sinus rhythm in an anesthetized dog previously injected in the LA with
Ad-HCN2-GFP. ECGs are interrupted during vagal stimulation (time-point 0). Shortly
therafter, asystole was induced. An idioventricular escape beat and two ectopic P waves
(
arrows
, lead I) originating from the LA are shown in the last part of the ECGs. Electrical
activity in LA precedes that in RA (from reference [36], with permission).
Adult human mesenchymal stem cells (hMSCs) are multipotent, which means that
they are, in contrast to embryonic stem cells, only able to differentiate into
mesenchymally derived cell lineages. Therefore, these cells always have to be
genetically modified when used to generate a biopacemaker. Potapova et al. [34]
described the delivery of HCN2 into hMSCs by electroporation. Unfortunately,
electroporation induces only transient expression of the HCN channels. To induce
long-term gene expression in these cells, a different method of genetic modification is
required. However, hMSCs expressing HCN2 were injected subepicardially into the
