In another step toward a stem cell therapy, researchers have identified a growth-factor chain of action that prompts bone marrow stem cells to repair cardiac tissue and reverse heart failure.
Earlier this researcg group showed that injecting bone marrow mesenchymal stem cells into skeletal muscle in an animal model increased two-fold the production of myocytes, a type of heart muscle cell.
"By thoroughly understanding the interplay of stem cells and host tissue, and characterizing stem-cell-derived growth factors," said Techung Lee, PhD, associate professor of biochemistry and biomedical engineering in the New York University at Buffalo School of Medicine and Biomedical Sciences. "it is possible to assemble a cocktail of these factors and use it for tissue repair, much like the use of insulin for diabetes patients."
Bone marrow mesenchymal stem cells [MSCs] possess an impressive ability to produce a plethora of growth factors, most of which remain to be characterized according to Lee.
"These growth factors appear to account for most of the observed therapeutic benefits in preclinical and clinical studies. Using skeletal muscle as a depot for the injected MSCs, we found that the MSC-derived growth factors activate production of host muscle tissue-derived growth factors."
The heart disease death rate has dropped significantly in the last three decades due to better treatments, resulting in large numbers of people living with heart failure. However, heart transplantation is the only therapy currently available to reverse the continual decline in heart function, and donor hearts are scarce.
Lee notes that current clinical trials of myocardial stem cell therapy require surgery, injecting the cells directly into the heart or into the heart muscle, invasive methods that can result in harmful scar tissue, arrhythmia, calcification or small vessel blockages. Lee's research group found that only 1-to-2 percent of MSCs infused into the myocardium actually grafted into the heart, and there was no evidence that they differentiated into heart muscle cells.
"For these reasons, and because patients with heart failure are not good surgical risks, it made sense to explore a non-invasive cell delivery approach," Lee notes.
Lee's group has shown that the instructive signal that generates the repair of cardiac tissue appears to come from at least a group of MSC-derived factors belonging to the IL-6 type cytokine family. Cytokines are small proteins made by the cells that act on other cells to stimulate or inhibit their function.
"These IL-6 type cytokines typically activate their cell/tissue targets through two specific proteins, known as JAK and STAT3, a cytosolic and a nuclear protein, respectively," explains Lee. "These cytokines then instruct the host cell to produce another panel of growth factors.
"The combined effects of the growth factors from injected stem cells and growth factors produced by host tissues cause tissue repair and achieve healing. Being able to use the factors for therapy rather than stem cells will make therapy to repair hearts much easier," Lee added.
Adapted from the New York University at Buffalo announcement.
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