Tel Aviv - Researchers from Israel have produced human heart tissue with 3-D printer. As "bio-ink" they used cardiomyocytes and endothelia that they had previously grown from induced pluripotent stem cells. In Advanced Science () the researchers report on muscle patch with “contractile potential” and mini-heart that has ventricles. A clinical application is currently not yet apparent.
The replacement heart for patient with severe heart failure could be obtained from his peritoneum in the future. On the one hand, cells would be isolated from small biopsy in the laboratory. These would be restored to the state of induced pluripotent stem cells (iPS) in order to grow heart muscle cells and endothelial cells from them. This is possible today, even if the low yield still causes problems.
All cells would be removed from the rest of the tissue sample, leaving matrix of collagenous fibers. One of the two “bio-inks” for the 3-D printer would then be produced from this mass. In addition to the connective tissue, this bio-ink would also contain the cardiomyocytes generated by the iPS.
These cells would later form into muscle fibers in bioreactor, which ultimately form heart muscle, which, when stimulated by pacemaker, performs regular contractions could. The technology for printing human tissue is in place today. There are 3-D printers that are gentle on cells and form “bio-ink” into blocks of tissue without destroying the cells contained therein.
The second “bio-ink” would consist of gelatin that binds with endothelial cells is mixed. This second “bio-ink” would take up the space for the later blood vessels in the printed heart. The course and diameter of the arteries and veins would be calculated beforehand on the computer so that an adequate blood supply for all cardiomyocytes would be guaranteed. In the bioreactor, the endothelial cells would then line the vessels. The gelatin would then be rinsed out. During the transplant, the vessels would be connected to the body's blood supply via bypasses. Then the heart from the 3-D printer could take over the pumping function of the old heart.
These are still distant visions, but the first steps have now been taken by team around Tal Dvir in Tel Aviv. The researchers first produced patch that was 2 millimeters thick, which was then transplanted into the peritoneum of animals. 7 days later the graft was removed and examined histologically. The heart cells had lengthened like tube and were arranged in parallel like in the real heart muscle.
They contained sarcomeres with the protein actin, which in the heart muscle together with the Protein myosin forms the contractile, i.e. motor apparatus. The researchers have not investigated whether the patches actually contract. A “patch” could one day be fixed on the heart muscle of heart attack patients in order to take over the task of the dead muscle parts and to prevent cardiomyopathy later. It is unclear whether this would work. But the first step has been done.
The second, much larger task would be to produce complete heart with ventricles and heart valves in the bioreactor - preferably from the patient's iPS himself, who then does not need immunosuppressants after transplant would. This vision is currently even further away than "heart patch". But second experiment by the stem cell researchers from Israel shows what production might look like one day - albeit in miniaturized form of 20 millimeter mini heart.
The principle is the same as with the patch. The printer, in turn, uses two “bio-inks” that contain cardiomyocytes and endothelial cells, from which the heart muscle and blood vessels are later formed. However, the connective tissue of the peritoneum was not suitable as basis for the "bio-ink" of the heart muscle. It is too soft and the heart would have collapsed after printing before the heart muscle cells could give it firm structure.
The researchers therefore switched to microparticles made of alginates, which could later be removed again if they were the heart muscle would have formed. The mini heart bred by the researchers has chambers, but it obviously lacks the heart valves and does not yet seem to have contractile properties. But here too, first step has been successful.