Progress toward healing scarred hearts

Scientists at the Murdoch Children’s Research Institute and UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have uncovered two specific markers that identify a stem cell able to generate heart muscle and the vessels that support heart function.

The discovery may eventually aid in identifying ways to use stem cells to regenerate damaged heart tissue following a heart attack.

The team included Dr David Elliot, leader of the Cardiac Development research group at Murdoch Childrens, student Rhys Skelton and Dr. Reza Ardehali from UCLA. The findings were published in Stem Cell Reports.

“In a major heart attack, a person loses an estimated one billion heart cells, which results in permanent scar tissue in the heart muscle. Our findings seek to unlock some of the mysteries of heart regeneration in order to move the possibility of cardiovascular cell therapies forward,” said Dr Ardehali, senior author on the study.

“We have now found a way to identify the right type of stem cells that create heart cells that successfully engraft when transplanted and also generate muscle tissue in the heart. This means we’re one step closer to developing cell-based therapies for people living with heart disease.”

The method is still years away from being tested in humans, but the findings are a significant step forward in the use of human embryonic stem cells for heart regeneration. The research team used human embryonic stem cells, which are capable of turning into any cell in the body, to create cardiac mesoderm cells. Cardiac mesoderm cells have some stem cell characteristics, but only generate specific cell types found in the heart.

Researchers pinpointed two distinct markers on cardiac mesoderm cells that specifically create heart muscle tissue and supporting vessels. They then transplanted these cells into an animal model and found that a significant number of the cells survived, integrated and produced cardiac cells, resulting in the regeneration of heart muscle and vessels.

The ultimate goal of the research is to one day develop regenerative heart cells from stem cells and then transplant them into the heart through a minimally invasive procedure, replacing scar tissue and restoring heart function.

Another study recently published by the team helps further this goal by outlining a novel approach to image, label and track transplanted cells in the heart using MRI, a common and non-invasive imaging technique. That study, which was published in the journal Stem Cells Translational Medicine, used specialised particles that are easily identified using an MRI. The labelling approach allowed the team to track cells in an animal model for up to 40 days after transplantation.

“Our findings show, for the first time, that specific markers can be used to isolate the right kind of early heart cells for transplantation, which is incredibly exciting,” said Dr Elliott.

The first author on both studies was Rhys Skelton, who has recently completed his PhD studies at Murdoch Children’s. He plans to return to UCLA as a postdoctoral scholar to continue his research on human embryonic stem cell-derived cardiac cells with the hope of one day developing a cell-based therapy for heart disease patients in need.

(Source: Murdoch Children’s Research Hospital, Stem Cell Reports)