Abstract 12857: The Use of “Cell Sheet” Technique Enhances the Therapeutic Effects of Skeletal Myoblast Transplantation with Elimination of Arrhythmogenicity
There is compelling experimental evidence to show that transplantation of skeletal myoblasts (SMBs) improves the function of failing hearts via paracrine effects. However, clinical application of this strategy has been curtailed due to arrhythmia occurrence and inconsistent outcomes observed in previous clinical trials of intramyocardial (IM) injection of SMBs. Severe inflammation and resultant global reduction of connexin43 have been reported to be causes of the arrhythmogenicity. Recent developments in bioengineering technology enabled production of “cell sheets” using temperature-responsive culture dishes, which allows retrieval of cells without enzymatic dissociation-related damages. We hypothesized that epicardial attachment of cell sheets would enhance retention, survival, and maintenance of functions of donor SMBs in the heart, with less myocardial injury, and therefore overcome the drawbacks of IM injection.
Methods & Results: After left coronary artery ligation in female Lewis rats, 4×106 SMBs derived from syngeneic male rats were transplanted by either IM injection (IM; n=12) or cell sheet attachment (Sheet; n=14). Sham-treated rats served as control (Cont; n=16). At day 28, the Sheet group achieved enhanced cardiac function, attenuated cardiac dilatation, and reduced infarct size, in association with a 2.5-fold increase in donor cell survival, compared to the IM group. Also, the increase in arrhythmogenesis in the IM group was attenuated in the Sheet group. While all rats in the IM group developed ventricular tachycardia, this was totally absent in the Sheet group. This reduced arrhythmogenicity in the Sheet group may be related to the negation of both the accumulation of CD45+ inflammatory cells and down-regulation of connexin43 in this group.
Conclusions: The cell sheet technique not only augmented the therapeutic benefits of SMB transplantation but also eliminated arrhythmogenicity, thereby paving the way for clinical application.
- © 2010 by American Heart Association, Inc.