TARA Biosystems, a firm based in New York City, and GlaxoSmithKline have managed to grow adult cardiac tissue inside the Biowire II platform developed by TARA, and have used this live tissue as a test bed for cardiac drug research.
Previously, growing cardiac tissue from human induced pluripotent stem cells that can be used in laboratory experiments has resulted in fetal-like cell phenotypes. Heart diseases, though, typically affect adult patients and the drugs that treat them will have different effects in adult and fetal cells.
The TARA and GaxoSmithKline team used the Biowire II platform to grow 3D engineered cardiac tissues and then delivered electrical stimulation to them over long periods of time. This led to the tissues having a phenotype that is more characteristic of the adult myocardium, including not exhibiting spontaneous beating that is one of the tell-tale signs of the fetal phenotype.
Using the adult cardiac tissue that they created, they subjected it to pharmacology studies that confirmed that the cells were behaving as adult cells would.
From the study abstract in journal Toxicological Sciences:
Pharmacology studies were performed in the ECTs to confirm the presence and functionality of pathways that modulate cardiac contractility in humans. Canonical responses were observed for compounds that act via the β-adrenergic/cAMP-mediated pathway, e.g. isoproterenol and milrinone; the L-type calcium channel, e.g. FPL64176 and nifedipine; and indirectly effect intracellular Ca2+ concentrations, e.g. digoxin. Expected positive inotropic responses were observed for compounds that modulate proteins of the cardiac sarcomere, e.g. omecamtiv mecarbil and levosimendan.
Study in journal Toxicological Sciences: Engineered Cardiac Tissues Generated in the Biowire
II: A Platform for Human-Based Drug Discovery
Product info page: Biowire II platform
