Researchers at the University of Cincinnati have discovered that applying a stem cell-infused patch in combination with the overexpression of a specific cell instruction molecule promoted the migration of cells to damaged heart tissue after a heart attack, which resulted in improved heart function in animal models. They also found that heart function improved more so than when stem cells were directly injected in heart tissue—a therapy that is being studied elsewhere.
Yi-Gang Wang and his research group in the department of pathology and laboratory medicine found that when a tri-cell patch, made up of heart muscle cells (cardiomyocytes, which can restore heart contractility), blood vessel cells (endothelial cells which build new blood vessels) and embryonic fibroblasts (to provide support to the cell structure), was applied to the surface of the damaged area of the heart, better outcomes in overall heart function resulted.
Following heart attacks, the heart tissue becomes damaged and scarred., Heart muscle cells die and the pumping function of the heart is reduced. While therapies exist, other researchers are examining stem cells injections directly into damaged heart muscle to see if contractile function can be restored.
This stem cell-based study differed other studies in that Wang’s s group wanted to determine if overexpression of a small RNA called miR-29 could enhance the effectiveness of an implanted cell patch. The strategy behind overproducing this gene was to reduce barriers between cells in the infarcted area. miR-29 is a small RNA molecule that is made in increased quantities once the heart undergoes a heart attack, and it seems to be involved in the scarring reaction that occurs after a heart attack. Overexpression of miR-29 should lead to enhanced regeneration of heart tissues and restoration of heart function after a heart attack.
Researchers first generated cardiac progenitor cells—cells that can become various cardiac tissue cell types—from induced pluripotent stem cells (iPSCs). These stem cells can differentiate into any type of cell in the body and are artificially derived from common body cells and are induced from a forced expression of several desired genes.
The iPSCs were then labeled with green fluorescent protein (GFP) and firefly luciferase (a glowing laboratory reagent) to help trace cell migration and proliferation into the animal’s system.
Researchers injected either the virus-mediated miR29b or a control material into the heart of the animal model and then experimentally induced a heart attack. Wang said, “These models allowed us to determine the possible benefits of miR29b and outcomes observed in two different control groups.”
Three days following the heart attack, researchers placed a cell patch on the damaged region and measured the expression of cardiac-related genes, collagen levels in the damaged tissue and scar formation-related signaling pathways. Collagen is the main component in scars and heart muscle scars that fill in heart tissue after heart attacks are no different.
One month after the cell patch implantation, echocardiograms were performed to evaluate heart function. Cells mobilized into the infarcted region of the heart. Analysis of these hearts by imaging determined the number of GFP-containing cells and the number of cells expressing firefly luciferase. The researchers found the number of GFP cells, bio-luminescence signals and heart function as a whole significantly increased in animals with cells that overexpressed miR-29b and were treated with the tri-cell patch.
According to Wang: “These findings show that an overexpression [sic] of miR-29 results in heart tissue changes that favor enhanced mobilization of desired cell types into infarct regions after heart attack, leading to improved heart function. Hopefully, one day such treatments will restore cardiac function in patients who have experienced a heart attack, leading to a longer and better quality of life.”