For the first time in history it has been achievedproduce in vitro and from induced pluripotent cells (iPS) a three-dimensional and vascularized fragment of human liveror that, after being transplanted into the skull and abdomen of mice, performsproper functions of the entire organ. According to the Japanese scientists responsible for the study, echoed by the SINC agency, in ten years they will be able to begin clinical trials in humans of transplant therapy with organ fragments.
The researchers, who publish their work in the journalNature, were inspired by the natural process of organ formation. During embryonic development, newly differentiated liver cells form a mass of tissue that immediately begins to vascularize, that is, to form blood vessels that carry nutrients to all cells. For this to occur, interactions and the exchange of signals with other cell types are essential. Mimicking this process that occurs naturally during development, the scientists produced liver cells by targeted differentiation and then cultured them in vitro alongside endothelial and mesenchymal cells. Thanks to these interactions, liver cells organized into visible three-dimensional structures, comparable to those that form in the embryo.
After transplanting this fragment into mice, the researchers observed thatthe vessels formed in vitro connected with those of the host and the organ began to grow and function properly. “The fragment is four or five centimeters long, too large to be introduced via the bloodstream, and it is difficult to implant it inside the host’s liver. That is why we chose two other implant sites for the mouse: the skull and the abdomen, ”explained Takanori Takebe.
Ten days later it began to be detectedalbumin–A protein produced by the liver– in the blood plasma of transplanted animals. To definitively prove that the new organ functioned like a human liver even in a mouse, the animals were given ketoprofen and debrisoquine, two products that mice and people metabolize differently. Both in the blood and in the urine of the mouse, substances typical of the human processing of both substances were detected.
“It’s very probable thatthis technique is applicable to different internal organs that develop similarly, such as the pancreas, lungs or kidneys. The pancreas is a promising candidate and we are already obtaining good results ”, predicts Takanori Takebe.
