Enhancing the Development of Heart Cells Using Materials Derived From Silk

In an exciting breakthrough that may have implications for stem cell-based treatment of heart disease, the lab of Dr. Deok-Ho Kim at the Institute for Stem Cell and Regenerative Medicine (ISCRM) has successfully used silk-based materials to enhance the development of stem-cell derived cardiomyocytes.

In a recent study detailed in the Journal of Materials Chemistry, Dr. Kim and his lab set out to promote improved cell development and maturation by creating a more natural environment for cultured cardiomyocytes. (The paper, entitled Conductive Silk-Polypyrrole Composite Scaffolds with Bioinspired Nanotopographic Cues for Cardiac Tissue Engineering was also featured in a special issue of the Journal recognizing quality research being conducted by emerging investigators of materials chemistry in the areas of biology and medicine.)

The research effort aimed to address a current challenge: While stem-cell derived cardiomyocytes are good for generating heart tissue for drug screening and in vivo therapies, they tend to be phenotypically deficient, meaning they are unable to generate sufficient amounts of contractile force and can be more prone to arrythmia. These immature cells are therefore not suitable for transplantation.

In the investigation, Dr. Kim’s team focused on the extracellular matrix, which is important for the structure and functioning of cardiomyocytes and organs. The research team was able to show that silk-derived materials could mimic the functioning the extracellular matrix, a finding that points to the benefits of growing stem cell cultures in vitro using bioinspired platforms.

Crucially, these materials had two important properties. First, they were electroconductive: they allowed electrical signals to pass between cells, which is essential for heart functioning. Second, they were nanopatterned: the materials used topographies that mimicked the structure of extracellular matrices found in native tissue.

Moving forward, the results of this study could have wider implications for developing platforms and techniques for further improving the maturity of stem cell-derived cardiomyocytes and other electrically-active cell types such as neurons and skeletal muscle. These cells can then be used for improved implantation-based therapies, as well as for engineering tissues that can be used as more representative in vitro drug screens and disease models. Future studies in Dr. Kim’s lab are focused on adapting and studying bioinspired cues in 3D for these applications.

Citation:

J. Mater. Chem. B, 2018, 6, 7185

Conductive silk–polypyrrole composite scaffolds with bioinspired nanotopographic cues for cardiac tissue engineering†
Jonathan H. Tsui, Nicholas A. Ostrovsky-Snider, David M. P. Yama, Jordan D. Donohue, Jong Seob Choi, Rakchanok Chavanachat, Jesse D. Larson, Amanda R. Murphy, and Deok-Ho Kim*

This work was supported by National Institutes of Health grants R01 HL135143 and R21 EB020132 (to D.-H. K.), and a
National Science Foundation grant DMR-1411292 (to A. R. M.).