A team of biomedical engineers has brought a step closer the day when we are able to regenerate tissue that is damaged in heart attacks.
Writing in the journal Scientific Reports, the team from the University of Michigan College of Engineering, Ann Arbor, explains how it transformed cells common in scar tissue into colonies of beating heart cells.
Previous attempts to reprogram cells in scar tissue directly into heart muscle cells have shown low success rates. The team believes one of the reasons has to do with the environment of the cells, which is poorly understood, as senior author Andrew Putnam, an associate professor of biomedical engineering, explains:
"Many reprogramming studies don't consider the environment that the cells are in - they don't consider anything other than the genes."
Yet, Prof. Putnam, who heads a lab that specializes in cell signaling in engineered tissue, says: "The environment can dictate the expression of those genes."
Encouraging the cells to form tight colonies could be a key step
For their study, the team tried turning scarring cells called fibroblasts, obtained from mouse embryos, into heart muscle cells by growing them in gels of varying stiffness.
To begin the conversion of fibroblasts into muscle cells, they infected them with a virus carrying genes expressed by stem cells. These "transgenes" fooled the fibroblasts into behaving like stem cells.
This step is usually skipped in direct reprogramming, but by including it, the team coaxed the cells to divide and form colonies. Otherwise they would have remained as "lone rangers."
Having a tight community of these progenitor cells may have helped with the next step because when they are developing, heart muscle cells are also cosy with their neighbors.
After a week of allowing the cells to develop in the different gels, the researchers added a protein that spurs growth of heart tissue by signaling to the progenitor cells to transform into heart muscle cells.
A few days after this, some of the cell colonies were contracting spontaneously, like colonies of heart muscle cells.
Best results occurred in fibrin and fibrin-collagen gels
The researchers found that the gels that produced the best results were fibrin and fibrin-collagen mixes. In these environments, as many as half of the colonies converted to heart muscle.
Fibrin gels are based on proteins that help blood platelets form into clots, while collagen-based gels are made from scaffolding proteins that give structure to tissue.
The team says it is not sure why fibrin appears so successful at supporting heart muscle cells. When under strain, fibrin hardens, unlike most materials that would stretch or weaken.
Prof. Putnam says perhaps the fibrin succeeded because heart muscle works better with a material that stiffens when it contracts.
There is still a way to go before findings like these are turned into something useful for heart medicine. For example, using viruses to insert the reprogramming genes is risky in that it can lead to tumors, and there needs to be a way to alter the scar tissue so it accepts cell reprogramming, or transplants of cell colonies grown outside the body.
Meanwhile, Medical News Today recently reported a study by a team at the University of Manchester in the UK, which showed how they reprogrammed mouse liver cells into pluripotent stem cells without using viruses.
Written by Catharine Paddock PhD