Researchers reprogram brain cells into heart cells

Penn researchers are the first to directly convert a non-heart cell type into a heart cell via RNA transfer, managing to change both a brain cell and a skin cell into a heart cell.

Being able to regenerate injured heart cells would give physicians the tools to repair and replace damaged tissue and ultimately save lives. So while researchers have spent more than a decade trying to reprogram cell types in general, changing them into heart cells has been a sort of holy grail.

Now, a team at the Perelman School of Medicine at the University of Pennsylvania has done just that--and is the first to directly convert a non-heart cell type into a heart cell via RNA transfer. In fact, the researchers reprogrammed both an astrocyte (a star-shaped brain cell) and a fibroblast (a skin cell) into heart cells.

The heart cell tCardiomyocyte (center) shows protein distribution (in green and red) indicative of a young cardiomyocyte. Tae Kyung Kim/University of Pennsylvania

"What's new about this approach for heart-cell generation is that we directly converted one cell type to another using RNA without an intermediate step," says James Eberwine, a pharmacology professor at Penn, in a news release.

Because a cell's signature is characterized by messenger RNAs (mRNAs), which act as a sort of blueprint for making a protein, the researchers introduced an excess amount of heart cell mRNAs into the host cells and let the new, abundant population essentially take over the smaller, indigenous one. This new population then directed DNA in the host nucleus to actually change the cell's RNA populations to the new heart cell ("tCardiomyocyte").

Ultimately, the heart-cell mRNAs are translated into heart-cell proteins, which influence gene expression in the host so that heart-cell genes are turned on and heart-cell-enriched proteins are made. The chain of events may be lengthy, but the process is direct.

The team's approach, called Transcriptome Induced Phenotype Remodeling, has been fine-tuned in Eberwine's lab in recent years.

While it may be a way off, the team says that reprogramming a patient's cells to be heart cells would enable personalized screening for efficacy of drug treatments and new drugs. It reports its findings online this week in the Proceedings of the National Academy of Sciences.

 

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