Stanford researchers use iPSCs to model heart disease in a dish and discover potential drug for treatment

One aspect of breakthrough iPSC technology is the ability to re-differentiate the iPSCs from patients, who may carry some disease-causing genetic variation, into cell types involved in the process of disease progression. This means that researchers can now study an individual’s or a family’s disease-involved cells in the laboratory and identify drugs that may be helpful to stop disease.

Indeed, Stanford researchers reported in July 2020 in the journal, Science Translational Medicine, that a familial condition of heart arrhythmia and progressive heart failure, a leading cause for heart transplantation, may benefit from treatment with known cholesterol-reducing drugs thanks to results of a drug screen in a laboratory model of iPSC-derived blood vessel cells and heart muscle cells in a dish. Remarkably, iPSC-derived heart muscle cells will actually beat in a dish.

Researchers collected skin cells and generated iPSCs from four generations of family members that carry the same variant in the LMNA gene, which is associated with a susceptibility to progressive heart failure. Individual’s iPSC were differentiated into the endothelial cells that line the blood vessels of the heart and body and into cardiomyocytes that are the beating muscle cells of the heart. The gene KLF2 was found to have reduced expression in the LMNA patient-specific blood vessel cells and was restored toward normal expression in the dish with the addition of drugs from the statin family of cholesterol-reducing drugs.

To understand which of the two cell types drives the progression of heart disease in the body, the two cell types were grown together in the same dish and the heart muscle cells were evaluated. They found that drug treatment or gene editing to correct the LMNA gene in the blood vessel cells could improve the function of the heart muscle cells through cell interactions between the two cell types. They concluded that the drug effect on KLF2 expression in blood vessel cells was able to induce an improvement in the properties of the patient’s iPSC-derived heart muscle cells. This result implied that the statin drugs could be an important therapeutic for people carrying this genetic variation and facing a high probability of heart failure.

The authors of the study called their results a virtual “Clinical trial in a dish,” demonstrating the remarkable ability of iPSC technology to advance not only regenerative medicine, but also drug discovery research. The paper can be found through PubMed through this link:

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