Biological Pacemakers Based on I - Biopacemaking - page 77

outset, much remains to be done. We have summarized this as follows: [3, 12, 13].
Whether the approach is with virus or stem cell, we need evidence that it is/is not
superior to the electronic pacemaker in terms of adaptability to the body's physiology
and duration of effectiveness. We also need evidence regarding long-term incidence
of inflammation, infection, rejection, and neoplasia, and for or against long-term
proarrhythmic potential. We need to understand if the construct is localized at the site
of implantation or migrates to other sites. Other toxicities of which we may not be
aware need to be looked for and delivery systems must be optimized. In addition, for
hMSCs (and indeed for any stem cells) we need evidence regarding persistence of the
administered cell types versus their differentiation into other cell types. In the latter
event, evidence regarding persistence of pace-maker function, in terms of physiologic
expression, current generated, and coupling to adjacent cells, will be essential.
Despite the challenges remaining, one point should be clear at present: that is, I f
alone is adequate—whether administered via virus or via plat-form—to drive the
heart. Given this information, and given the need to use the simplest possible system
to generate pacemaker function, we plan to persist with this approach. We do this
because of the belief that the more complexity that is brought into the system, the
more that can go wrong. Hence, we wish to avoid additional potentially confounding
components unless further research proves them absolutely essential.
Acknowledgments. The authors express their gratitude to Ms Laureen Pagan for her
careful attention to the preparation of the manuscript. The studies described were
supported by USPHS-NHLBI grants HL 28958 and HL 67101, and by Guidant
Corporation.
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