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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

Pluripotent stem cells could be differentiated into artificial blood vessels

Scientists have developed a strategy to differentiate pluripotent stem cells into contractile smooth muscle cells, a cell type which together with endothelial cells could be used to create artificial arteries.

Cardiovascular diseases account for 31% of all global deaths. Occlusive peripheral arterial disease, one of the leading causes of mortality worldwide, is caused by blockage or narrowing of an artery in the legs due to atherosclerosis, resulting in decreased blood flow.

Balloon angioplasty, stents, and bypass surgery are the treatment options available for patients with occlusive arterial disease. However, restenosis, a condition where the narrowing recurs after corrective surgery, is commonly observed because of intimal hyperplasia.

During intimal hyperplasia, smooth muscle cells (SMCs) that are normally contractile in nature switches its phenotype to more synthetic nature. During this phenomenon called as contractile to synthetic phenotypic switching, contractile protein (MYH11) expression is decreased and proliferation, migration, and extracellular matrix production is increased.

Factors that promote the differentiation of contractile SMCs therefore could be used to minimize the chance of developing intimal hyperplasia.

In the present study published in Stem Cell Reports, Dr James Thomson and team at Morgridge Institute for Research (Madison, USA) developed a strategy to generate more contractile SMCs from pluripotent stem cells. Using a high-throughput differentiation screen, they identified RepSox as a factor that promotes contractile SMC generation.

Subsequent studies revealed that RepSox induced SMCs to exhibit a more contractile phenotype. Interestingly, RepSox inhibited intimal hyperplasia caused by contractile to synthetic phenotypic switching of SMCs in a rat balloon injury model.

The study provides a strategy to differentiate pluripotent stem cells into contractile SMCs which could be a stepping stone for constructing artificial blood vessels. In addition, the study also suggests a strategy to identify drugs that could inhibit intimal hyperplasia.

Source: A Human Pluripotent Stem Cell-Based Screen for Smooth Muscle Cell Differentiation and Maturation Identifies Inhibitors of Intimal Hyperplasia. Zhang J et al., Stem Cell Reports, May 2019. DOI

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