Biomedical Engineering Reference
In-Depth Information
canine left ventricular wall and faster escape rhythms compared to controls, were
recorded during sinus arrest. One should realize that hMSCs are not equipped with the
complete set of ion channels to either initiate an AP or to hyperpolarize the RMP to a
membrane potential range where HCN channels are active. Therefore, electric
coupling to cardiac myocytes is of crucial importance. When the cardiomyocytes are
well coupled to stem cells, they are able to hyperpolarize the hMSCs electrotonically,
and activate HCN channel opening. This could be followed by a slow phase 4
depolarization in the hMSCs, which would result in the initiation of APs in cardiac
myocytes (Fig. 5).
Fig. 5.
Pacemaker activity initiated from myocyte or human mesenchymal stem cell (
hMSC
).
Top Sinoatrial node cell or gene therapy targeted myocyte connected via gap junctions to a
surrounding myocyte. Action potentials (
inset
) are initiated by slow diastolic depolarization
resulting from current flowing through HCN channels.
Bottom
HCN channels overexpressed in
hMSCs, these channels can only be activated if the membrane potential is hyperpolarized by
the adjacent myocyte. Channel activation will result in excitation of the adjacent myocyte via
gap junctions, which will initiate action potential formation (from reference [39], with
permission).
An advantage of hMSCs, is that they are possibly immunoprivileged, i.e., they
have not elicited major immune responses in limited studies [25]. However, a
drawback is that it is uncertain how these cells may differentiate over time after
transplantation. It is possible that these cells differentiate into cardiac cells but
differentiation into other cells cannot be ruled out [37]. In addition, concerns are
rising concerning the risk of neoplasia, rejection, or migration to other sites [39].
