Biomedical Engineering Reference
In-Depth Information
response. This was important because we believe that in the tradeoff between
biological and electronic pacemakers, any need for immunosuppression using the
former approach would render it clinically undesirable. hMSCs are obtained readily
commercially or from the bone marrow and are identified by the presence of CD44
and CD29 surface markers as well as by the absence of other markers (Fig. 6) that are
specific for hematopoietic progenitor cells.
Using a gene chip analysis, we determined that the hMSCs do not carry message
for HCN isoforms; importantly, they do have a significant message level for the gap
junctional protein, connexin 43. This is critical because the theory behind platform
therapy was that the hMSC would be loaded with the gene of interest (HCN2 in this
case) and implanted into myocardium [13]. However, having a cell loaded with a signal
would not work unless the cell formed functional connections with its neighbors. The
rationale for this approach is summarized in Fig. 7. In brief, in the normal sinus node,
hyperpolarization of the membrane initiates inward (
I
f
) current which generates
g
Fig. 8.
Identification of connexins in gap junctions of human mesenchymal stem cells
(hMSCs). Immunostaining of Cx43 (
a
), Cx40 (
b
), and Cx45 (
c
).
d
Immunoblot analysis of
Cx43 in canine ventricular myocytes and hMSCs. Migration of molecular weight markers is
indicated to the
right
of the blot (reprinted by permission from reference [14]).
