AN UNEXPECTED DISCOVERY
The study worked with mice using two types of heart stem cells—bone marrow mononuclear cells and cardiac progenitor cells. As the researchers tested their findings under different conditions, they discovered that live stem cells were not necessary for inducing the immune response they had seen. In fact, injecting dead cells produced the same outcome.
Further, they observed that zymosan, an inert chemical designed to induce an innate immune response, also provided a slightly greater and longer-lasting benefit to the heart than injecting stem cells or dead cell debris.
Be it stem cells or zymosan, the injections altered immune cell responses that significantly decreased the formation of extracellular matrix connective tissue in the injury areas, while also improving the mechanical properties of the scar itself.
The authors conclude: “Injected hearts produced a significantly greater change in passive force over increasing stretch, a profile that was more like uninjured hearts.”
The researchers also found that the response occurs only when the injections occur directly into the hearts, as opposed to infusing stem cells via the circulatory system.
“Most of the stem cell clinical trials were incorrectly designed because they infuse cells into the vasculature,” Molkentin explains. “Our results show that the injected material has to go directly into the heart tissue flanking the infarct region. This is where the healing is occurring and where the macrophages can work their magic.”