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Scientists 'Print' World's First Heart With Human Bioinks, Next 'Teach Them To Behave' Like Hearts


Scientists 'Print' World's First Heart With Human Bioinks, Next 'Teach Them To Behave' Like Hearts

Robin Seaton Jefferson Apr 18, 2019, 06:29pm
Researchers at Tel Aviv University (TAU) in Israel reported this week that they have “printed” the world’s first 3D vascularized engineered heart using a patient’s own cells and biological materials. Their findings were published on April 15 in a study in Advanced Science.

Until now scientists in regenerative medicine have been successful in printing only simple tissues without blood vessels. But in what TAU researchers are calling "a major breakthrough," they say they have engineered a heart that “completely matches the cellular and anatomical properties of the patient,” and soon hope to test the heart in animals.
“This is the first time anyone anywhere has successfully engineered and printed an entire heart replete with cells, blood vessels, ventricles and chambers," said Prof. Tal Dvir of TAU's School of Molecular Cell Biology and BiotechnologyDepartment of Materials Science and EngineeringCenter for Nanoscience and Nanotechnology and Sagol Center for Regenerative Biotechnology“We are now investigating the physiological behavior of the engineered tissues under controlled conditions in the lab. If we will get positive results, we will move on to transplantation experiments in animal models,”
Research for the study was conducted by Dvir, Dr. Assaf Shapira of TAU’s Faculty of Life Sciences and Nadav Moor, a doctoral student in Dvir’s lab.
But while the news is remarkable, Dvir said a considerable amount of research has yet to be done, and researchers hope their discovery will be just the tip of the iceberg in the capabilities of regenerative medicine. “We hope that this development, together with inspiring, elegant works that are being conducted by our colleagues worldwide, will advance the field of regenerative medicine and take tissue engineering a step forward," he said. "We hope to see more and more significant breakthroughs in the near future. These will get us closer and closer to the ultimate goal of clinical application and maybe one day we will get the opportunity to replace injured or diseased organs with engineered ones. However, we need to remember that this research is in its infancy and a great deal of research and development (R&D) needs to be devoted.”
According to the Centers for Disease Control and Prevention (CDC), heart disease remains the leading cause of death for both men and women, and about 610,000 people die of heart disease in the United States every year. That’s 1 in every 4 deaths.
While heart transplantation remains the only true “cure” for end-stage cardiac disease, there is a dire shortage of heart donors. And since demand continues to far outpace the supply, Dvir said, “the need to develop new approaches to regenerate the diseased heart is urgent.”
So, though the newly printed heart is smallabout a third the size of an actual human heartit’s an enormous step in the right direction, Dvir said. “At this stage, our 3D heart is small, the size of a rabbit’s heart,” he said. “But larger human hearts require the same technology.”
The TAU researchers' heart is made from human cells and patient-specific biological materials, Dvir said. “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,” he 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.”
Researchers used a biopsy of fatty tissue taken from patients for their study. “The cellular and a-cellular materials of the tissue were then separated,” Dvir explained. “While the cells were reprogrammed to become pluripotent stem 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.’ After being mixed with the hydrogel, the cells were efficiently differentiated to cardiac or endothelial cells to create patient-specific, immune-compatible cardiac patches with blood vessels and, subsequently, an entire heart.”
Dvir said the use of materials directly from the patient is crucial to successfully engineering tissues and organs. “The biocompatibility of engineered materials is crucial to eliminating the risk of implant rejection, which jeopardizes the success of such treatments,” he said. “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.”
The researchers are now planning on culturing the printed hearts in the lab and “teaching them to behave” like hearts, Dvir said. But there is much work to be done. Next, researchers plan to transplant the 3D-printed heart in animal models.
“We need to develop the printed heart further,” he said. “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.”
Dvir said he can’t give an exact time when patients with heart disease can expect to benefit from the printed heart, only that his research should give them new hope. “Unfortunately, we cannot predict the time that is needed in order to bring these developments to clinical application,” he said. “It would also be irresponsible for us to do so. We hope that the field of tissue engineering and regenerative medicine will develop fast, but we need to be patient as much work still needs to be done. Maybe, in ten years, there will be organ printers in the finest hospitals around the world, and these procedures will be conducted routinely.”
American Friends of Tel Aviv University supports Israel’s most influential, comprehensive and sought-after center of higher learning, Tel Aviv University (TAU) which is ranked ninth in the world, and first in Israel, for producing startup founders of billion-dollar. To date, 2,500 U.S. patents have been filed by Tel Aviv University researchers — ranking TAU #1 in Israel, #10 outside the U.S. and #43 in the world.
Robin Seaton Jefferson lives just outside of St. Louis with her husband of 25 years and two daughters. Find her on Twitter and Facebook @SeatonJefferson or contact her at rsjreporter@charter.net. 

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