Posts Tagged ‘bioreactor’

A Realistic 3D Model of a Human Heart Ventricle

Reported: Irina Robu, PhD

Scientists from Harvard University designed a working 3D model of a human heart’s left ventricle whose objective is to replace animal models with human models and patient-specific human models. The discovery could improve how diseases are studied, drugs are tested and lead to patient-specific treatments for various heart ailments, including arrhythmia.

The researchers reinvented the tissue’s unique structure, where parallel myocardial fibers act as a scaffold to direct brick-shaped heart cells to align and accumulate end-to-end and form a hollow, cone-shaped structure. When the heart beats, the cells expand and contract. The new tissue is engineered using a nanofiber scaffold that is seeded with human heart cells and acts like a 3D template to guide the cells and their assembly into ventricle chambers that beat in vitro.

In this research, they used a nanofiber production platform called pull spinning, which uses a high-speed rotating bristle that slopes into a polymer reservoir and pulls a droplet from the solution into a jet, to recreate the scaffold. The fiber travels in a spiral trajectory and solidifies before detaching from the bristle and moving toward a collector.

The team made the ventricle using a combination of biodegradable polyester and gelatin fibers collected on a rotating collector in which all of the fibers align in the same direction. The scientists then cultured the ventricle with rat myocytes or human cardiomyocytes from induced stem cells and found that within three to five days, a thin wall of tissue covered the scaffold and the cells were beating in synch. The procedure allowed control and monitor of the calcium and insert a catheter to study the pressure and volume of the beating ventricle.

The tissue is then exposed to a drug similar to adrenaline called isoproterenol and measured as the beat-rate increased.  They also poked holes in the ventricle to mimic a myocardial infarction and studied the effect of the heart attack in a petri dish. The ventricle is then conditioned in a self-contained bioreactor with separate chambers for optional valve inserts, extra access ports for catheters and ventricular assist capabilities. The cultures were run for six months and stable pressure-volume loops were measured.

With this new model, scientists might study the heart’s function by many of the same tools now being used in the clinic, including pressure-volume loops and ultrasound. They hope to use patient-derived, pre-differentiated stem cells to seed the ventricles, letting for more high-throughput production of the tissue.





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