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Researchers at Tel Aviv University say they have invented the first fully personalized tissue implant, made up of a patient’s own materials and cells, paving the way to engineering a variety of implants from just one small fatty tissue biopsy and making the risk of an immune response to an organ implant “virtually disappear.”
In their study, the researchers took fatty tissue from patients’ stomachs and separated the cells from other, acellular material. The researchers then manipulated the cells to transform them into pluripotent stem cells — cells that can develop into any kind of cells, from neurons to cardiac cells to spinal cord cells.
“This procedure to create stem cells from adult cells in the body is a well-established procedure that has been done,” said Prof. Tal Dvir of TAU’s Department of Biotechnology, Department of Materials Science and Engineering, Center for Nanoscience and Nanotechnology and the Sagol Center for Regenerative Biotechnology, who led the research for the study.
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Then they took the acellular material and transformed it into a personalized hydrogel, a biomaterial that supports cells and allows them to form a functioning tissue. Combining the hydrogel with the newly created stem cells, the scientists then created personalized tissue implants of many types (spinal cord, dopaminergic, cardiac and fatty tissues). The materials could then be implanted in animals, showing minimal immune response.
The researchers have also shown that these patient-specific biomaterials do not induce an immune response in humans. In both animals and human blood, Dvir said, there was no immune response to the personalized materials, “making the risk of an immune response to an organ implant virtually disappear.”
The illustration shows the neuronal network inside a spinal cord implant (Dr. Reuven Edri at Prof. Tal Dvir’s lab; Tel Aviv University)
“Until now researchers used synthetic materials or animal materials to support the stem cells to create the tissue for the implant,” said Dvir in a phone interview. But such implants can induce an immune response that leads to rejection of the implanted tissue. This means that patients receiving engineered tissues or any other biomaterial-based implants — either synthetic or from other animals — are treated with immuno-suppressors, which themselves endanger the health of the patient.
For this reason, said Dvir, the development of such implants is still in the experimental phase only.
“In our case, we rely on the patients’ own cells and their own materials, without triggering any adverse response from the immune system,” he said. “We create patient-specific cells and personalized hydrogels, and we showed, in mice, that there was no immune response after implantation.”
The researchers tested mice with their own materials and also with foreign materials — derived from other mice or from pigs — and in the latter case the implants triggered the immune response.
In a second phase, the researchers simulated the implants in the blood cells of humans, when both the cells and the hydrogel derived from the patient. without triggering an immune response.
“There is a huge difference,” he said. “When the patient recognizes its own biomaterials there is no immune response.”
The system can be used to engineer cardiac, spinal cord, cortical and other tissue implants to treat different diseases, said Dvir. “Since both the cells and the material used derive from the patient, the implant does not provoke an immune response, ensuring proper regeneration of the damaged organ.”
“We could create and implant cells that can help regenerate spinal cord cells, or those of an infarcted heart or brain trauma,” he said. To combat Parkinson’s, patients could be implanted with neurons that secrete dopamine.
The research was conducted by Dvir’s postdoctoral researcher Dr. Reuven Edri and doctoral students Nadav Noor and Idan Gal, in collaboration with Prof. Dan Peer and Prof. Irit Gat Viks of TAU’s Department of Cell Research and Immunology and Prof. Lior Heller of Assaf HaRofeh Medical Center in Israel. It was recently published in Advanced Materials.
“With our technology, we can engineer any tissue type, and after transplantation we can efficiently regenerate any diseased or injured organ — a heart after a heart attack, a brain after trauma or with Parkinson’s disease, a spinal cord after injury,” said Dvir. “In addition, we can engineer adipogenic (fatty tissue) implants for reconstructive surgeries or cosmetics. These implants will not be rejected by the body.”
The researchers are at the moment regenerating an injured spinal cord and an infarcted heart with spinal cord and cardiac implants. They have also begun to investigate the potential of human dopaminergic implants to treat Parkinson’s disease in animal models. At a later stage, the researchers plan to regenerate other organs, including intestines and eyes, using the patients’ own materials and cells.
“We want to get to do trials on humans as soon as possible,” he said. But to do this a startup company would need to be set up to determine the best way forward.
“We believe that the technology of engineering fully personalized tissue implants of any type will allow us to regenerate any organ with a minimal risk of immune response,” Dvir said. “The sky is the limit.”
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