Tel Aviv University Scientists Print First 3D Heart Using Patient’s Own Cells

April 15, 2019

4 min read

For the first time ever, Israeli scientists have created a vascularized human heart that completely matches the immunological, cellular, biochemical and anatomical properties of a human patient, using a 3D printer.

Until now, scientists in regenerative medicine – a field that integrates biology and technology – have been successful in printing only simple tissues without blood vessels.

This major medical breakthrough at Tel Aviv University has just been published in the journal Advanced Science by team leader Prof. Tal Dvir under the title 3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts.” He was assisted by Nadav Noor, Dr. Assaf ShapiraReuven Edri, Idan Gal and Lior Wertheim.

“This is the first time anyone anywhere has successfully engineered and printed an entire heart replete with cells, blood vessels, ventricles and chambers,” said Dvir of the materials science and engineering department of TAU’s School of Molecular Cell Biology and Biotechnology, the Center for Nanoscience and Nanotechnology and the Sagol Center for Regenerative Biotechnology.

The huge achievement brings hope that within a decade or so, instead of sick people dying due to failing organs or waiting a long time for a donor heart from a brain-dead individual, hospitals will be able to print it or other organs from the cells of the would-be recipient.

Heart disease is the leading cause of death among both men and women in the US and most of the modern world and the second-leading cause, after cancer, in Israel.  Heart transplantation is currently the only treatment available to patients with end-stage heart failure. Given the severe shortage of heart donors, the need to develop new approaches to regenerate the diseased heart is urgent.

(Courtesy Tel Aviv University)

“This heart is made from human cells and patient-specific biological materials. In our process, these materials serve as the bio-inks, substances made of sugars and proteins that can be used for 3D printing of complex tissue models,” Dvir said. “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.”

“At this stage, our 3D heart is small, the size of a rabbit’s heart,” noted. Dvir. But larger human hearts could be created using the same technology, he added.

For the research, a biopsy of fatty tissue was taken from patients. The cellular and a-cellular materials of the tissue were then separated. While the cells were reprogrammed to become pluripotent stem cells and efficiently differentiated to cardiac or endothelial cells, the extracellular matrix (ECM) – a three-dimensional network of extracellular macromolecules such as collagen and glycoproteins – were processed into a personalized hydrogel that served as the printing “ink.”

The differentiated cells were then mixed with the bio-inks and used to 3D-print patient-specific, immune-compatible cardiac patches with blood vessels and, subsequently, an entire heart. Dvir said that the use of “native” patient-specific materials is crucial to successfully engineering tissues and organs.

A 3D printed, small-scaled human heart engineered from the patient’s own materials and cells. (Courtesy Tel Aviv University)

“The biocompatibility of engineered materials is crucial to eliminating the risk of implant rejection, which jeopardizes the success of such treatments,” Dvir stressed. “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-print thick, vascularized and perfusable [that blood can be pushed through vessels) cardiac tissues that completely match the immunological, cellular, biochemical and anatomical properties of the patient.”

The researchers are now planning on culturing the printed hearts in the lab and “teaching them to behave” like hearts, Dvir said. They then plan to transplant the 3D-printed heart into animal models.

“We have to develop the printed heart further,” he concluded. “The cells need to form a pumping ability; they can currently contract, but we need them to work together. Our hope is that we will succeed and prove our method’s efficacy and usefulness. “Maybe, in 10 years, there will be organ printers in the finest hospitals around the world, and these procedures will be conducted routinely.”

Last year, Dvir and his lab team produced the first implant of completely personalized tissue, comprised of a patient’s own stomach cells and other materials. Taking acellular material and turning it into a biological material that supports cells and makes it possible to form a functioning tissue, this was a significant step towards the current breakthrough.

The material did not trigger an immune response that would have caused the tissue to be rejected by the recipient. Dvir said the system could be used to engineer cardiac, spinal cord, cortical and other tissue implants to treat various diseases.

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