Stem cell exosomes used to stimulate healing of damaged mouse hearts

Written by Alexandra Thompson

Researchers from Temple University School of Medicine (TUSM; PA, USA) are using the communications vesicles secreted by stem cells to induce the self-repair of damaged hearts

When heart muscle is damaged in a heart attack it is unable to repair the damage. In the USA congestive heart failure ultimately contributes to or causes one out of nine deaths, and heart disease is the leading killer in the nation, showing the pressing need for an effective therapy. Stem cells are being investigated as a therapy, but do not always survive transplantation in effective numbers and can carry risk of generating teratomas.

In the current study, Dr Raj Kishore, Director of the Stem Cell Therapy Program at the Center for Translational Medicine at Temple University School of Medicine (TUSM; PA, USA), and colleagues investigated whether extracellular vesicles from embryonic stem cells (ESCs) would help the repair of the damaged heart tissue, using a murine model of myocardial infarction.

After infarction mice received either exosomes from ESCs or fibroblasts, with those receiving the ESC-derived vesicles demonstrating improved heart function compared with the control fibroblast group. The ESC group demonstrated an increased number of myocardial cells surviving, decreased scarring, decreased apoptosis, greater capillary development around the injury site and a marked increase in cardiac progenitor cells, which survived and created new heart cells. The stem cell exosoome group demonstrated a stronger heartbeat and decreased cardiac enlargement enlargement (a compensatory mechanism occurring after heart damage).

Kishore commented: “If your goal is to protect the heart, this is a pretty important finding… 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.”

The team next looked to specify what within the exosomes may be causing the regeneration-promoting activity. When one of the microRNAs found in the exosomes, miR-294, was introduced to cardiac stem cells in the laboratory and was found to replicate many of the effects of delivery of the entire exosomes. “To a large extent, this micro-RNA alone can recapitulate the activity of the exosome,” Kishore stated. “But we can never say it is responsible for all of the response because embryonic stem cell exosomes have many other microRNAs.” The next steps of this project will be to see how both exosome and specific miRNA delivery in large animals and eventually in human trials can assist heart repair.