Washington: Researchers have discovered a stem cell therapy that might help the heart recuperate from an attack. This study published in the journal Nature reported that injecting living or even dead heart stem cells into the injured hearts of mice triggers an acute inflammatory process, which in turn generates a wound healing-like response to enhance the mechanical properties of the injured area.
Mediated by macrophage cells of the immune system, the secondary healing process provided a modest benefit to heart function after a heart attack, according to the principal investigator Jeffery Molkentin, PhD, director of Molecular Cardiovascular Microbiology a Cincinnati Children's Hospital Medical Center and a professor of the Howard Hughes Medical Institute (HHMI).
"The innate immune response acutely altered cellular activity around the injured area of the heart so that it healed with a more optimised scar and improved contractile properties," Molkentin said. The findings build on a 2014 study published by the same research team. As in that earlier study, the current paper shows that injecting c-kit positive heart stem cells into damaged hearts as a strategy to regenerate cardiomyocytes doesn't work.
The findings prompted Molkentin and his colleagues to conclude that there is a need to "re-evaluate the current planned cell therapy based clinical trials to ask how this therapy might really work." Researchers worked with two types of heart stem cells currently used in the clinical trials -- bone marrow mononuclear cells and cardiac progenitor cells.
As they went through the process of testing and re-verifying their data under different conditions, they were surprised to discover that in addition to the two types of stem cells, injecting dead cells or even an inert chemical called zymosan also provided benefit to the heart by optimising the healing process. Zymosan is a substance designed to induce an innate immune response.
They reported that stem cells or zymosan therapies tested in this study 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. Researchers also found that stem cells and other therapeutic substances like zymosan have to be injected directly into the hearts surrounding the area of infarction injury.
"Most of the current trials were also incorrectly designed because they infuse cells into the vasculature. 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," Molkentin explained.