Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 398

Adult skeletal myoblasts (SMs) were the first type of SC therapy used to treat heart disease. These cells harbor precursor cells, called satellite cells, which have regenerative potential due in part to their characteristic expression of PAX3 and PAX7, without expression of CSPG4. In normal skeletal muscle, these cells quiescently exist, but with injury, signals cause them to proliferate, forming multinucleated myotubes. Studies suggest that this process also occurs when SMs are introduced to injured cardiac muscle. Clinical trials of SMs have extensively explored their use to treat congestive heart failure (CHF). SM treatments are commonly autologous, and harvested SMs are abundantly available, easy to proliferate in culture, and relatively more resistant to ischemic conditions than cardiac cells. Despite this potential, clinical trials have not resulted in clinically significant improvements for heart disease. The MARVEL trial at Duke University demonstrated that in patients with severe CHF and ejection fraction (EF) < 35 percent, no significant improvement resulted in functional capacity analyzed by the walk test and the Minnesota Living With Heart Failure Score after intramyocardial-SM injections. In the U.S.-collaborated SEISMIC trial, no significant difference in global left ventricular (LV)-EF resulted between patients with low, high, or placebo-dose SM treatments after 6 months, as verified by multigated acquisition scans. Importantly, several studies demonstrate that SMs do not form electromechanical connections with surrounding cardiomyocytes due to their inability to express connexin 43. Consequently, several clinical trials have demonstrated adverse events such as ventricular tachyarrhythmia.