Getting Stem Cells Ready To Repair Hearts

Using a drug and proteins known as laminins, scientists have found a way to induce stem cells to differentiate into cardiac muscle-like cells, fibroblast-like cells and epithelial-like cells.

AsianScientist (Apr. 9, 2019) – An international team of scientists has used a natural protein and a synthetic molecule to induce stem cells to turn into cells that make up the heart. They published their findings in the journal Cell Reports.

The self-regeneration of human heart muscle following injury is extremely limited. Scientists have been studying techniques to prompt different kinds of stem cells to differentiate into heart cell precursors, which could then help rebuild heart muscle fibers.

However, most existing approaches have not yet met regulations set forth by the US Food and Drug Administration and the European Medicines Agency for regenerative therapies. This is because regulatory bodies require stem cell-derived precursors to be prepared from human-only cells and in cultures that use clearly defined chemicals and no animal components. The method must also be reproducible, and the cells must have clear characteristics while not leading to adverse side effects when injected.

In this study, scientists led by Professor Karl Tryggvason of the Duke-National University of Singapore Medical School, Singapore, investigated using a heart muscle associated protein called laminin to promote the differentiation of human embryonic stem cells into heart cell precursors. Laminins attach to the outer parts of cell membranes and are thought to play a role in the differentiation of precursor cells into other types of cells. Several types of laminins exist.

The team produced laminin-221 in the laboratory and used it to coat a culture of pluripotent human embryonic stem cells. They also used another type of laminin, laminin-521, to support the growth of the stem cells, as well as an organic compound called CHIR99021 to boost stem cell differentiation.

The researchers reported that their approach led to the differentiation of three main subpopulations of cardiovascular precursor cells: cardiac muscle-like cells, fibroblast-like cells and epithelial-like cells. They verified that their precursors did not include cells with a propensity to develop into tumors.

Using a mouse model of cardiovascular disease, the researchers injected nine- and 11-day-old cardiovascular precursor cells into damaged heart tissue and found these precursor cells differentiated into cardiac muscle fiber bundles that survived in the heart for at least 12 weeks. The heart functions of the mice also improved.

“These results suggest a role for the use of laminins in cardiac muscle cell differentiation, and may lead the development of clinical-quality cardiovascular progenitor cells for regenerative cardiology in humans,” said Tryggvason.

Future research is needed to investigate other cell subpopulations that may form with this technique, and whether they can intensify new heart muscle growth in living animals.

The article can be found at: Yap et al. (2019) In Vivo Generation of Post-infarct Human Cardiac Muscle by Laminin-Promoted Cardiovascular Progenitors.


Source: Duke-NUS Medical School; Photo: Shutterstock.
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