Small Molecules Prime Stem Cells for Cardiac Repair Role

Cardiovascular researchers have described a method for manipulating human stem cells known as peripheral blood mononuclear cells (PBMCs) in such a way that they transformed into immature cardiac cells capable of repairing heart damage in an animal model.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) screened nearly 147,000 chemical compounds during their search for drugs that would stimulate PBMCs to begin producing RNA and proteins normally found in cardiac cells. They found that the most successful candidate compounds were a family of sulfonyl-hydrazone (Shz) small molecules.

Human PCMBs were cultured with the compound Shz-3 for three days, then for seven days without the drug. The treated cells were then injected into the hearts of rats with heart damage. Results published in the April 17, 2008, online edition of the Proceedings of the [U.S.] National Academy of Sciences (PNAS) revealed that after seven days, the function of the rats' hearts had significantly improved, and after three weeks, the organs contracted as strongly as they did before the damage. The recovery of cardiac function correlated with persistence of viable human cells that expressed human-specific cardiac mRNAs and proteins.

"This functional test is a good first step,” said senior author Dr. Jay Schneider, assistant professor of internal medicine at the University of Texas Southwestern Medical Center. "What this shows is that this drug can act on blood stem cells that are already being used in other clinical trials. This may speed its movement into clinical trials for heart repair.”


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University of Texas Southwestern Medical Center