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 Shapira, Reuven Edri, Idan Gal and Lior Wertheim.
The scientists created a live heart in a revolutionary new 3D printing process that combines human tissue taken from a patient. Until now, scientists in regenerative medicine – a field that integrates biology and technology – have been successful in printing only simple tissues without blood vessels.
#BREAKING: Israeli scientists successfully create a 3D heart with human tissue.
They hope that in the future, this technology could replace donating organs. Wow! pic.twitter.com/zqceyqJ8zc
— Hananya Naftali (@HananyaNaftali) April 15, 2019
In November, Tel Aviv University researchers said they invented the first fully personalized tissue implant engineered from a patient’s own biomaterials and cells, paving the way for new technology that would make it possible to develop any kind of tissue implant from one small fatty tissue biopsy.
Now, these same researchers created a real heart using their innovative process at the Laboratory for Tissue Engineering and Regenerative Medicine led by Professor Tal Dvir, an associate professor at Tel Aviv University’s Department of Molecular Microbiology and Biotechnology.
The process involved taking fatty tissue, after which the cellular and a-cellular materials 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,” Tel Aviv University said in a statement.
The differentiated cells were then mixed with the bio-inks and were used to 3D-print patient-specific, immune-compatible cardiac patches with blood vessels and, subsequently, an entire, tiny heart.
Cardiovascular diseases are the number one cause of death worldwide, according to the World Health Organization. In 2016 alone, an estimated 17.9 million people died from heart diseases, a majority due to heart attack and stroke.
Heart transplantation is currently the only treatment available to patients with end-stage heart failure. And with a shortage of heart donors, this scientific breakthrough development may blaze a trail in the medical world, paving the way for a potential revolution in organ and tissue transplantation.
“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,” Professor 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,” he added.
Tel Aviv University explained that in the current method for tissue engineering for regenerative medicine, cells are isolated from the patient and cultured in biomaterials, synthetic or natural, derived from plants or animals, to assemble into a functional tissue. After transplantation, they may induce an immune response that can lead to rejection of the implanted tissue.
Patients who are recipients of engineered tissues or other implants often require treatment with immuno-suppressors, which can endanger the health of the patient.
With this development, “patients will no longer have to wait for transplants or take medications to prevent their rejection. Instead, the needed organs will be printed, fully personalized for every patient,” the university said in a statement.
The process was outlined in an article titled “3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts” published on Monday in “Advanced Science,” a peer-reviewed scientific journal.
Research for the study was conducted jointly by Professor Dvir, Dr. Assaf Shapira of TAU’s Faculty of Life Sciences, and Nadav Moor, a doctoral student in the lab.
In their study, the team worked with two models: one made from human tissue, and another made from rat tissue.
In the press briefing, Professor Dvir emphasized that the technology “won’t be available in clinics or hospitals tomorrow, we are in the very early stages of this technology.” But, he said, in about a decade, as 3D printing technology evolves, hospitals and clinics may have these printers on site.
Professor Dvir explained that the heart, currently the size of that of a rabbit’s, will need to undergo a maturing process in bioreactors – a system that supports a biologically active environment – to keep the cells alive and grow them to accommodate a life-sized heart, while “teaching” them to organize and interact with each other and achieve pumping ability.
Currently, he said, “the cells are capable of contracting separately but not pumping.”
The printing process takes between 3-4 hours, but the maturing process takes about a month, after which the scientists will begin testing on small animals such as rabbits and rats.
They hope this will happen in a year or two.
Dr. Shapira tells NoCamels that the scientists will 3D-print hearts for these respective animals from their own tissues after which they will conduct transplants and begin clinical trials.
The potential is great. According to Professor Dvir, the use of “native” patient-specific materials 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-print thick, vascularized and perfusable cardiac tissues that completely match the immunological, cellular, biochemical and anatomical properties of the patient.”
But there are also significant hurdles. First is cost. Professor Dvir says the printing process for the heart cost “a few thousand shekels” in a lab environment, but should the technology be commercialized in the future, it will likely be expensive.
The scientists will have to print a human-sized heart and that could pose a challenge. “How do you print all the cells and blood vessels for a heart?” asked Professor Dvir in reference to the resolution limitations currently of 3D printers.
“We must take into consideration that 3D printing technology is also developing,” he said.
“Maybe, in 10 years, there will be organ printers in the finest hospitals around the world, and these procedures will be conducted routinely,” he said.
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