A handful of biotech companies have been laboring for years to turn stem cells into treatments that can repair damaged tissue after a heart attack, but with limited success. A team from the Cincinnati Children's Hospital Medical Center tracked stem cells injected into the hearts of mice, and what they found could explain why this particular attempt at regenerative medicine has not proven effective—and inspire new ideas for repairing damaged heart tissue.
The researchers injected both live and dead heart stem cells into mice with damaged hearts and discovered that the procedure touched off extreme inflammation. That inflammatory response generated a healing process, which in turn improved the mechanical properties of the injured area, they reported in the journal Nature.
During the study, the scientists used two types of stem cells that have been tested for the treatment of damaged heart tissue in clinical trials: cardiac progenitor cells and bone marrow mononuclear cells. They also tried injecting the chemical zymosan, which has been shown to prompt an immune response that can promote healing.
All three treatments activated macrophage cells from the immune system, which helped the animals’ hearts heal “with a more optimized scar and improved contractile properties,” said lead investigator Jeffery Molkentin, Ph.D., director of Molecular Cardiovascular Microbiology at Cincinnati Children's Hospital Medical Center and professor at the Howard Hughes Medical Institute, in a statement.
Problem is, the initial goal of injecting stem cells into patients with damaged hearts was to regenerate cardiomyocytes. The Cincinnati team had previously reported that c-kit+ cardiac progenitor cells only produce tiny amounts of new cardiomyocytes—not nearly enough to provide any therapeutic value.
This new study validated that finding, leading Molkentin and colleagues to propose that cardiac researchers “re-evaluate the current planned cell therapy based clinical trials to ask how this therapy might really work.”
What’s more, the researchers found that stem cells and zymosan were only effective if they were injected directly into mouse hearts in the areas where the damage had occurred. This approach is at odds with most stem cell clinical trials, which involve infusing cells into the circulatory system.
“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 said.
The findings from the Cincinnati team could prove valuable in a field that has seen its share of disappointments. Australia-based Mesoblast, for one, released results from a phase 2 trial last year that showed patients who received injections of mesenchymal precursor cells did not improve to the point where they could stop using their left ventricular assist devices.
And the National Heart, Lung, and Blood Institute of the National Institutes of Health had to halt a trial testing c-kit+ cells and mesenchymal stem cells in patients with heart failure because of safety concerns.
The Cincinnati Children's Hospital researchers believe their findings could inspire new regenerative approaches to treating heart disease. They are now planning further studies focused on harnessing the healing power of macrophages.