A new paper in the journal Circulation Research by a research team from the Temple University School of Medicine (TUSM) has examined the use of tiny stem cell-based vesicles to help limit the damage caused by a heart attack. Even those these experiments were performed with laboratory mice, the result are very promising.
A heart attack tends to badly damage it, and since the heart has little innate ability to repair itself, it has to compensate by growing large and flabby, which can lead to congestive heart failure, Congestive heart failure is currently responsible for one in nine deaths in the United States.
The research team of Raj Kishore at the Temple University School of Medicine turned to exosomes to heal the heart. Exosomes are tiny sacks secreted by cells that act as messengers that pass messengers between cells in various parts of the body. While these extracellular vesicles are secreted by nearly all types of cell, exosomes from stem cells might be a useful tool in mitigating damage caused by heart attacks.
“If your goal is to protect the heart, this is a pretty important finding,” Dr. Kishore said. “You can robustly increase the heart’s ability to repair itself without using the stem cells themselves. Our work shows a unique way to regenerate the heart using secreted vesicles from embryonic stem cells.” Kishore’s group is also beginning to determine those members of this “work crew” within the vesicles may be responsible for the damage repair.
Previous studies have shown that injecting damaged hearts with stem cells increases heart function after a heart attack. However, the injected cells tend to not survive very long when placed in the damaged heart, and most of their benefits are due to molecules that the administered stem cells secrete. Pluripotent stem cells (embryonic stem cells, for example) run the risk of creating a tumor made up of a mass of cells of different tissue types, known as a teratoma. Therefore, Khan’s tram approached the problem from a slightly different angle by injecting only the exosomes made by stem cells. It was known that this would avoid the teratoma problem, and could have positive effects on damaged heart tissue.
The study examined mice that had suffered heart attacks. These animals were split into two groups; one group received exosomes from mouse embryonic stem cells, and the other group were injected with fibroblast exosomes.
The results were extremely promising. The mice that had received stem cell-derived exosomes exhibited improved heart function, less scar tissue, lower levels of programmed cell death and better capillary development around the damaged area. There was also a higher presence of cardiac progenitor cells – the heart’s own stem cells – in the stem cell exosome-injected mice. Overall, the heartbeat of the mice was stronger than those in the control group, with less unhealthy enlargement of the organ.
Khan and others examined an abundant gene-regulating molecule (microRNA) from the stem cell-derived exosomes, known as miR-294. They introduced this microRNA into cultured cardiac stem cells. This microRNA recapitulated many of the positive effects of the stem cell exosomes that had been observed in the animal study.
Khan and his coworker plan to continue their research by studying the effects of individual microRNAs on damaged heart tissue.
“Our work shows that the best way to regenerate the heart is to augment the self-repair capabilities and increase the heart’s own capacity to heal,” says researcher Dr Mohsin Khan. “This way, we’re avoiding risks associated with teratoma formation and other potential complications of using full stem cells. It’s an exciting development in the field of heart disease.”