Cardiomyocyte Molds to Improve Cardiac Cell Therapy

Researchers at Michigan Tech and Harvard Medical School have developed a new way to create cardiomyocytes from induced pluripotent stem cells (iPSCs), for improved cardiac cell therapy. The team developed a culture mold that mimics the physiological conditions under which cardiomyocytes grow. When the team tested the molds, they found that the cells matured more quickly and showed enhanced functionality, compared with traditional 2D culture.

These lab-fabricated, fluorescently stained cardiomyocytes—heart muscle cells—exhibit the maturation and functionality of heart cells grown within a heart. – MTU

iPSCs show significant potential for cardiac regenerative medicine, as researchers can use biochemical cues to “program” them into a cardiomyocyte-like cell, which shows regenerative efficacy in damaged cardiac muscle. However, creating fully functional cardiac cells can be a challenge.

“Unfortunately stem cell therapeutics don’t have high success rates partly because the cells are not mature and fully functional. The maturation and functionality are essential,” said Parisa Pour Shahid Saeed Abadi, a researcher involved in the study.

Rather than focusing on biochemical cues, these researchers looked at modifying the 3D environment of the cells, with a view to creating an environment more like that found in the heart.

Programming induced pluripotent stem cells into heart muscle cells requires biochemical and biomechanical cues. Growing the cells in a three-dimensional substrate that mimics the natural heart environment produces better cells. – MTU

“The mechanical properties of substrates play an important role in the cell behavior because the mechanical cues that cells sense in the actual (heart) environment is unique,” said Abadi. “We are using biochemical and biomechanical cues to enhance the differentiation and maturation. If we don’t take advantage of the physical cues and only rely on chemical cues, the process suffers from low efficiency and batch-to-batch inconsistency.”

Induced pluripotent stem cell-derived cardiomyocytes beating in substrate. – MTU

Using photolithography to shape a polydimethylsiloxane substrate and micropatterning to alter the substrate surface, the researchers developed 3D molds that mimic the natural forces and pressures that cardiomyocytes experience in the heart. The micropatterning alters the cell cytoskeleton and nuclear shape of cells cultured in the molds, causing changes in gene expression. This results in more robust, mature and functional cardiomyocyte-like cells. As the cells mature, they begin to beat, and more closely resemble mature, native cardiomyocytes.

The researchers plan to test the cells in an animal model of cardiac disease, and also investigate the potential of enhancing electrical conductivity between the cells, to facilitate the cell-cell communication that occurs in the heart.

Study in Advanced Functional Materials: Engineering of Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Using Substrates with Multiscale Topography…

Via: Michigan Tech…