Scientists Create World's First 3D-Printed Heart Using Patient's Own Cells

A small 3D-printed human heart engineered from the patient's own materials and cells. Advanced Science/© 2019 Nadav Noor, Assaf Shapira, Reuven Edri, Idan Gal, Lior Wertheim, Tal Dvir

Researchers at Tel Aviv University have successfully printed the world’s first 3D heart using a patient’s own cells and biological materials to “completely match the immunological, cellular, biochemical, and anatomical properties of the patient.”

Until now, researchers have only been able to 3D-print simple tissues lacking blood vessels.

"This heart is made from human cells and patient-specific biological materials. In our process these materials serve as the bioinks, substances made of sugars and proteins that can be used for 3D printing of complex tissue models," said lead researcher Tal Dvir in a statement. "People have managed to 3D-print the structure of a heart in the past, but not with cells or with blood vessels. Our results demonstrate the potential of our approach for engineering personalized tissue and organ replacement in the future." 

F, G) A printed heart within a support bath. H) After extraction, the left and right ventricles were injected with red and blue dyes, respectively, in order to demonstrate hollow chambers and the septum in‐between them. Advanced Science

Describing their work in Advanced Science, the research team started by taking biopsies of fatty tissues from abdominal structures known as the omentum in both humans and pigs. The tissue's cellular materials were separated from those that weren’t and reprogrammed to become pluripotent stem cells, “master cells” able to make cells from all three body layers with the potential to produce any cell or tissue in the body. The team then made the extracellular matrix – made up of collagen and glycoproteins – into a hydrogel used as the printing “ink”. Cells were mixed with the hydrogel and then differentiated into cardiac or endothelial cells (those that line the interior surface of blood and lymphatic vessels) to create patient-specific, immune-compatible cardiac patches complete with blood vessels and, ultimately, an entire heart bioengineered from “native” patient-specific materials.

Though promising, the team is quick to remind us that their hearts are not yet ready for human transplantation.

"At this stage, our 3D heart is small, the size of a rabbit's heart," said Dvir. "But larger human hearts require the same technology."

For starters, creating a human heart would take much longer and require billions of cells – not just millions. Furthermore, the cherry-sized hearts don’t necessarily behave like hearts, requiring researchers to further develop and “train” them to be like human hearts and form a pumping ability. Currently, the cells can contract but do not work together.

Regardless, the development is a massive step for the advancement of organ transplantation. Heart disease is the leading cause of death in men and women in the US, with heart transplants being the only treatment available to those with end-stage heart failure. Not only does a shortage of donors require the development of new strategies, but creating hearts that jive with a patient’s unique biological makeup could prevent the risk of rejection.

"The biocompatibility of engineered materials is crucial to eliminating the risk of implant rejection, which jeopardizes the success of such treatments," said Dvir. "Ideally, the biomaterial should possess the same biochemical, mechanical and topographical properties of the patient's own tissues. Here, we can report a simple approach to 3D-printed thick, vascularized and perfusable cardiac tissues that completely match the immunological, cellular, biochemical and anatomical properties of the patient."

After “training” the hearts to efficiently pump, the team hopes to transplant them into animals for further testing.

Cells from a patient's omentum tissue are separated and processed into a personalized thermoresponsive hydrogel. The cells are reprogrammed to become pluripotent and are then differentiated to cardiomyocytes and endothelial cells before encapsulation within the hydrogel to generate the bioinks used for printing. The bioinks are then printed to engineer vascularized patches and complex cellularized structures. Advanced Science

 

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