Wnt Inhibitors in hESC Cardiogenesis (p 360)
Willems et al have identified a molecular booster of cardiomyocyte production.
Given the relative scarcity of hearts available for transplant, researchers are looking for ways to repair injured or diseased hearts by replacing lost myocytes. Much hope is placed in stem cell strategies, but whether such cells come from within the body or from an external source – such as embryonic stem (ES) cells – improvements in the understanding and efficiency of cardiomyocyte differentiation are needed. Willems et al tested 550 small molecules individually on ES-derived mesoderm cells to see which, if any, would improve cardiomyocyte differentiation. They found just one – a molecule called IWR, which stands for inhibitor of the Wnt signaling response. Wnt is a secreted signal responsible for the differentiation and development of a variety of tissue types. When added to ES-derived mesoderm cells, IWR promoted the expression of cardiac-specific genes and converted up to 30% of cells into cardiomyocytes – a whopping 200-fold increase over controls. Other, better-known Wnt inhibitors also improved cardiomyocyte differentiation, the team showed. Since IWR boosts cardiomyocyte differentiation of ES cells, it will be interesting to see whether it can do the same for the heart's own stem cells as well.
Antibody Tagging for Imaging and Cell Delivery (p 365)
Ta et al have a new technique for delivering molecules and cells to specific body locations. Their first target: blood clots.
The delivery of drugs, molecules, and therapeutic cells to particular body tissues, while often desired, is rarely easy. One strategy is to conjugate the molecule/cell of interest to an antibody that recognizes the target tissue. But such an approach often links the antibody to cargo in an array of conformations, some of which reduce antibody function. Ta et al have now developed a site-specific conjugation approach that creates just one antibody-cargo conformation, while maintaining antibody activity. To achieve this, the team used a bacterial enzyme that both recognizes and covalently links 2 peptide tag sequences. One tag was introduced into the antibody sequence – in this case an antibody that recognizes activated platelets. The other was added to the cargo –fluorescent proteins, magnetic particles, or cells. The fluorescence-conjugated antibodies bound activated platelets tightly in vitro, while in vivo the magnetic particle and cell-conjugated antibodies homed specifically to blood clots (which contain activated platelets). The new technique could be used to study, and potentially treat, thrombotic, atherosclerotic, and inflammatory diseases, say the team, but could also be adapted to target molecules or cells to any desired tissue.
CD34+ Cell Therapy for Refactory Angina (p 428)
There is new hope for patients with refractory angina, say Losordo et al.
Therapies for angina include lifestyle changes, such as weight loss and smoking cessation, medications such as anti-platelet drugs, beta-blockers, calcium channel blockers and nitrates, as well as surgical interventions. There are some patients, however – currently 850,000 in the U.S. – that have exhausted these options, and suffer from so-called refractory angina. Recent pre-clinical and early clinical data suggest that CD34+ cells might help. Although CD34+ cells are hematopoietic stem cells, they can also give rise to endothelial cells, secrete pro-angiogenic factors, and promote neovascularization in ischemic heart tissue. Losordo et al now report data from a phase II double-blind trial in which 167 refractory angina patients had either their own CD34+ cells or placebo injected into their hearts. After six months, patients that received CD34+ cells had fewer episodes of angina and showed an increased tolerance to exercise compared with patients injected with placebo. Mortality was also lower. Interestingly, a lower dose of CD34+ cells (100,000) worked better than a higher dose (500,000). The researchers suggest that perhaps the high dose exceeds the optimum cell number for efficient paracrine effects. Whatever the case, the good news is that refractory angina patients could have access to another treatment option after all.
Written by Ruth Williams
- © 2011 American Heart Association, Inc.