Molecules Can Make Heart Muscle from Stem Cells

Researchers have identified small molecules that can cause embryonic stem cells to selectively differentiate into cardiomyocytes, or heart muscle cells.

Normally, cells develop along a pathway of increasing specialization, but scientists have been seeking ways to selectively differentiate stem cells into specific cell types. Researchers theorized that if stem cells were exposed to certain synthetic chemicals, they might selectively differentiate. To test this hypothesis, they screened about 100,000 small molecules from a combinatorial small molecule library they had previously synthesized.

Working with this assortment, the researchers designed a method to identify molecules able to differentiate the mouse embryonic stem cells into heart muscle cells. They engineered embryonal carcinoma (EC) cells with a reporter gene encoding a protein called luciferase, which they inserted downstream of the promoter sequence of a gene that is only expressed in cardiomyocytes. Then the EC cells were placed into separate wells and different chemicals from the library were added to each. The engineered EC cells induced to become heart muscle cells expressed luciferase, which made the well glow, distinguishing it from tens of thousands of other wells when examined with high-throughput screening equipment.

A number of molecules were able to induce the differentiation of EC cells into cardiomyocytes, and the researchers chose one called Cardiogenol C for further studies. Using Cardiogenol C, scientists reported they could selectively induce more than half of the stem cells in their tests to differentiate into cardiac muscle cells. Existing methods are reported to result in merely 5% of the stem cells becoming the desired cell type.

"It's hard to control which specific lineage the stem cells differentiate into,” said first author Xu Wu, a doctoral candidate in the Kellogg School of Science and Technology at the Scripps Research Institute (La Jolla CA, USA; www.scripps.edu). "We have discovered small molecules that can turn embryonic stem cells into heart muscle cells.” Also taking part in the study were researchers from the Genomics Institute of the Novartis Research Foundation (San Diego, CA, USA).




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