Cardiac muscle restitution, or true regeneration, is an unmet need in the treatment of myocardial infarction (MI), prompting a decade of study with stem cells of many kinds. Among key obstacles to effective cardiac cell grafting are the cost of autologous stem cell-derived cardiomyocytes, the ethical implications of using embryonic stem cell (ESC) products, immunological barriers to allogeneic ...

Expression of the two isoforms of cardiac myosin heavy chain (MHC), MHC alpha and MHC beta, in mammals is regulated postnatally by a variety of stimuli, including serum hormone levels. Less is known about the factors that regulate myosin gene expression in rapidly growing cardiac muscle in embryos. Using isoform-specific 35S-labeled cRNA probes corresponding to the two MHC genes and the two myo...

Smooth muscle cells (SMCs) have evolved to subserve a variety of diverse functions in higher vertebrates, including modulation of arterial tone, regulation of airway resistance, and control of gastrointestinal motility. The diverse functional capacities of SMCs are ultimately determined by the expression of genes encoding SMC-restricted contractile and cytoskeletal proteins, intracellular enzym...

Several clinical trials of bone marrow stem cell therapy for myocardial infarction are ongoing, but the mechanistic basis for any potential therapeutic effect is currently unclear. A growing body of evidence suggests that the potential improvement in cardiac function is largely independent of cardiac muscle regeneration. A study by Fazel et al. in this issue of the JCI provides evidence that bo...

nous network within muscle cells, which is the analogue of the endoplasmic reticulum (ER) in other cells. This organelle has a variety of functions, of which release of Ca2+ to the cytosol and reuptake into the interior compartment (the lumen) of the SR are the most important. Rapid release of Ca2+ through a Ca2+ release channel (ryanodine receptor) in the skeletal muscle SR is responsible for ...

The effect of changes in temperature on the calcium sensitivity of tension development was examined in permeabilized cellular preparations of rat ventricle and rabbit psoas muscle. Maximum force and Ca2+ sensitivity of force development increased with temperature in both muscle types. Cardiac muscle was more sensitive to changes in temperature than skeletal muscle in the range 10-15 degrees C. ...

We determined the actin isotypes encoded by 30 actin cDNA clones previously isolated from an adult human muscle cDNA library. Using 3' untranslated region probes derived from a-skeletal, 13and -y-actin cDNAs and from an a-cardiac actin genomic clone, we showed that 28 of the cDNAs correspond to a-skeletal actin transcripts. Unexpectedly, however, the remaining two cDNA clones proved to derive f...

Cardiac muscle regeneration after injury is limited by "irreversible" cell cycle exit. Telomere shortening is one postulated basis for replicative senescence, via down-regulation of telomerase reverse transcriptase (TERT); telomere dysfunction also is associated with greater sensitivity to apoptosis. Forced expression of TERT in cardiac muscle in mice was sufficient to rescue telomerase activit...

Myocardial repair using stem-cell therapy has become a promising therapeutic tool. However, many questions concerning a precise functional integration of injected cells remain unanswered. The use of cardiac pre-committed cells may improve integration, as these cells may complete their differentiation in the myocardium reducing fibrosis and restoring muscle function. We have previously demonstra...