- Researchers develop a 3D model of human heart left ventricle to study disease and test drugs.
- To build this, they used gelatin fibers, biodegradable polyester and human cardiomyocytes or rat myocytes.
The heart is examined at various scales in vitro (procedures performed in cells, microorganisms outside their normal biological context), from bioengineered tissues to cellular assays and organ-on-chip microphysiological systems.
Now, researchers at Harvard University have developed a 3D model of a human heart left ventricle with contractile cardiac chambers. It can be used for testing drug effects, studying diseases, and building person-specific heart treatments like arrhythmia.
To build this model, they used a nanofiber scaffold (behaves like a three-dimensional template) implanted with human heart cells. This enables scientists to examine heart functions using clinical tools and methods, like ultrasound and pressure-volume loops.
The team has spent more than 10 years working up to the objective of creating an entire artificial heart. Their long term goal is to replace the animal models with patient-specific human models, and build tissues that can replicate feature of a particular organ.
The model cardiac chamber is based on systematic structure and functional attributes of the human left ventricle. In the native heart, parallel myocardial fibers, which behave as scaffold, guide cells to align end-to-end, producing a hollow structure. These cells shrink and expand (like an accordion) when heart beats.
How Did They Create Scaffold and Ventricle?
Pull spinning | Credit: Disease Biophysics Group/Harvard SEAS
To create the scaffold, they used pull spinning – a platform for generating nanofiber. Its high-speed bristle goes into the solution of a polymer and pulls drops from the pool into a jet. The fiber moves in a spiral path and hardens before being detached from the bristle.
For the ventricle part, they used gelatin fibers (from rotating collector) and biodegradable polyester. All fibers were aligned in a single direction due to consistent spinning of the collector. Due to these aligned fibers, all cells get aligned too, mimicking native cells.
The next step is to culture the ventricle with human cardiomyocytes or rat myocytes. Within 3 to 5 days, the scaffold was covered by a thin layer of tissue and cells started beating synchronously.
A 3D model of a left heart ventricle | Credit: Michael Rosnach and Luke MacQueen
After this, the researchers were able to analyze and control the propagation of calcium, and put a catheter to examine the volume and pressure of the beating ventricle.
To test their model, they exposed the tissue to a similar drug to adrenaline called isoproterenol, and monitored as the beating rate raised to the level of rat and human heart-beat rate. Also, they poked several holes in the ventricle for mimicking myocardial infarction. This enabled them to study the effects of heart attack in a petri dish.
The self-contained bioreactor | Credit: John Ferrier/Harvard SEAS
In order to better examine the model over an extended period of time, the team developed a bioreactor with independent chambers for optional valve inserts, optional ventricular assist capabilities and additional access port for catheters. Specifically, they cultured the ventricles for half a year and analyzed stable pressure-volume loops, using human cardiomyocytes from induced stem cells.
Bioengineering ventricle attached to a catheter | Credit: Luke MacQueen/Harvard SEAS
The team plans to utilize pre-differentiated, person-specific stem cells to seed the ventricles, for higher throughput tissue production. We are still far from developing a four chamber heart, but as the scientists claim, the progress is accelerating.