Biomedical Engineering Reference
In-Depth Information
The next steps involved catheter injection of the same construct into the canine
proximal left ventricular conducting system, under fluoroscopic control [5]. Animals
so injected demonstrated idioventricular rhythms having rates of 50-60 bpm when
sinus rhythm was suppressed by vagal stimulation. For the HCN2 group, the rhythms
mapped to the site of injection (Fig. 4). When bundle branch tissues were removed from
the heart and studied with microelectrodes, we found that automaticity in those injected
with HCN2 exceeded that in control preparations. As shown in Fig. 5, there was a
significantly greater spontaneous rate generated by the HCN2 injected bundle branches
than by those injected with either saline or virus carrying GFP, alone.
Our most recent work has expanded in two areas as reported in preliminary fashion
[6]. First, we have tested the possibility that injecting an adenovirus carrying the E324A
mutant described above might provide an effective alternative to HCN2 in experiments in
vivo. While the demonstration of favorable activation kinetics in situ suggested E324A-
based pacemakers might increase pacemaker rate, we were concerned the lesser
magnitude of current expression might offset the potential benefit. We also believed that
regardless of its effects on basal rate, E324A might bring about a greater sympathetic
response than HCN2. We found that E324A-infected dogs manifested basal rates that did
not differ significantly from those of HCN2-in-fected animals, while their catecholamine-
responsive-ness was greater. As such, the E324A mutant represents only a subtle
variation on the parent, HCN2, construct.
The other area of recent interest has been the exploration of tandem therapy with
electronic and biological pacemakers [6]. In brief, we have found that using the two
together provides an electronic baseline rate that insures a heartbeat even if the biological
component fails, while the biological component provides the autonomic rate
responsiveness so important to normal physiologic function. In addition, the electronic
component provides a means for monitoring the function of the biological pacemaker
while the latter will likely prolong the battery life of the former. Hence, the two together
should provide a reasonable pairing for any phase 1 study that may be considered and
may provide significant therapeutic advantage for some time thereafter.
Filtered bone marrow cells
Mononuclear bone marrow cells
Hematopoietic
progenitor cells CD45+
(1 -2% of human bone marrow)
Non -hematopoietic
progenitor cells
CD45 -
Routine characterization of hMSC
includes testing for surface antigens
and functional testing for
differentiation down specific lineage
pathways (adipogenic, chondrogenic
and osteogenic lineages).
Mesenchymal stem cells
CD29+, CD44+, CD166+
CD14 -, CD34 -, CD45 -
(0.05% of human bone marrow)
Fig. 6.
Origin of adult human mesenchymal stem cells
