Heart rebuilt with stem cells learns to beat again

Mouse heart muscle precursor cells created from embryonic stem cells at the Gladstone Institutes in the lab of Bruce Conklin.

The past few months we have written about two themes emerging in stem cell science: neighborhood matters when you want to get a stem cell to grow up into a functional adult; and the best cell to get the job done is often a “middleman,” a cell that is part of the way down the path from stem cell to functional adult tissue called a precursor cell.

Now a team from the University of Pittsburgh has used cells they describe as multipotential cardiovascular progenitors (MCP) to rebuild a mouse heart. They called them “multipotential” because they could form all three types of cells found in the adult heart. They placed these middleman cells on the scaffold of a mouse heart that was left over after they used chemicals to remove all the living cells. That framework provided the neighborhood necessary to tell the MCPs to become the three different cells in the right places.

The researchers started with a human skin sample and reprogrammed those cells into the iPS type of stem cell. They then used various genetic factors to get them to mature to the point of being MCPs.

The team published the research in Nature Communication and a news website wrote this story from the University’s press release. It quotes the senior researcher, Lei Yang, on both the importance of the middleman cell and the scaffold as a neighborhood:

“This process makes MCPs, which are precursor cells that can further differentiate into three kinds of cells the heart uses, including cardiomyocytes, endothelial cells and smooth muscle cells. Nobody has tried using these MCPs for heart regeneration before. It turns out that the heart’s extracellular matrix — the material that is the substrate of heart scaffold — can send signals to guide the MCPs into becoming the specialized cells that are needed for proper heart function.” 

After a few weeks in the lab the heart began to beat, but at a slower rate than either a human or mouse heart, just 40 to 50 beats a minute. Before this technology could be considered for human heart transplants the new heart would need to be made stronger and researchers would need to figure out how to also rebuild the heart’s electrical system that tells the organ to speed up or slow down.

But the team’s immediate goal is to use MCPs and smaller scaffolds to make patches of heart muscle to mend small areas damaged by a heart attack.

Other teams are using stem cells to deliver protein factors to damaged hearts that can signal our body’s naturally occurring healing mechanisms to do a better job. CIRM funds several teams working a mending broken hearts, You can read about that work here.

Don Gibbons

One thought on “Heart rebuilt with stem cells learns to beat again

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