It goes without saying that the heart is an important organ, but it’s difficult to study how it reacts to diseases and medications. Researchers at Harvard have now grown a model of a human left ventricle that spontaneously beats, marking a substantial step towards engineering entire hearts for more accurate testing of new treatments.
Traditionally, testing new drugs and treatments, as well as modeling disease, has been done on animals. The problem is, the results don’t always carry across to humans, and getting your hands on the real thing is tricky because, well people still need them. Realistic models are the way to go, with scientists in the past growing mini-hearts by “humanizing” rat hearts, or using living cells to create heart-on-a-chip devices.
The Harvard team engineered the new model by seeding human heart cells onto a nanofiber scaffold. First the fibers, made up of a combination of biodegradable polyester and gelatin, were spun into a cone shape on a collector device, which aligns all the fibers in the same direction thanks to its spin.
With that basic structure in place, the team then introduced living heart cells grown from induced stem cells, in some cases from rats and in others from humans. Within three to five days, these cells had grown into a thin wall of tissue across the whole scaffold, and were beating in a natural, stable way.
To test how well the model reacted to stimuli, the researchers then dosed it with isoproterenol, and it began to beat faster just like a real heart would. They even induced a heart attack by poking holes in it.
For a longer term study, the researchers built a bioreactor to safely house the ventricle, complete with ports where they could insert valves, catheters and other devices to help with the experiment. With this setup, the ventricles kept going steady for six months.
“The fact that we can study this ventricle over long periods of time is really good news for studying the progression of diseases in patients as well as drug therapies that take a while to act,” says Luke MacQueen, first author of the study.
For the next step, the team plans to use heart cells gathered from patients, which would provide a more accurate and personalized model for how a disease would progress or how well a treatment would work in that person. These models, the researchers say, would share the genetic background of the patient, along with mutations that might change the results from a generic model. Eventually, a full four-chambered heart is the target.
“The long-term objective of this project is to replace or supplement animal models with human models and especially patient-specific human models,” says MacQueen. “In the future, patient stem cells could be collected and used to build tissue models that replicate some of the features of their whole organ.”
The research was published in the journal Nature Biomedical Engineering.