The researchers set out with a simple question: could the scaffold left behind in so-called ‘decellularized’ hearts guide pluripotent cells to form new heart tissues without the need for external cues? To find the answer, the researchers used the hearts of mice and removed all heart cells with a detergent solution, leaving just the extracellular matrix, a fibrous tangle made primarily of collagen protein and growth factors.
Next, the researchers repopulated the scaffold with either human embryonic stem cells (ESCs), which can change into all cell types of the human body, or mesendodermal cells (MECs), which can give rise to heart cells only. After two weeks of culturing, the researchers characterized the resulting cells in a laboratory dish and by growing the cells in mice, and found that both the ESCs and MECs expressed a number of key genes involved in heart muscle function. “This indicates that the signaling instructions present in the extracellular matrix can direct pluripotent stem cells to differentiate to heart cells,” says Wan.
However, there were some important differences between the tissues depending on the cell source. Only heart tissues derived from MECs expressed genes for the myosin light chain, a critical motor protein involved in muscle contraction, whereas those from ESCs preferentially expressed genes for the myosin heavy chain. Independent analyses of stem cell-derived heart muscle tissues have shown that the more mature cells tend to favor the expression of the light chain over the heavy chain. Although the IBN team did not observe any beating cells in their scaffold, they believe that MECs alone would be the better choice as they are the more committed cell type.
In addition to forming heart muscle cells, the seeded stem and progenitor cells also gave rise to endothelial cells, another crucial type of heart tissue, with the differentiated cell type ultimately dependent on where the implanted cells came into contact with the scaffold. The findings underscore the value of using pluripotent cells to generate a potentially limitless supply of bioartificial hearts.
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