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Researchers develop technology to produce transplantable liver in the laboratory

Publicado em 06 abril 2021

Researchers at the Human Genome and Stem Cell Research Center (Hugsel) Was sponsored by the Institute of Biological Sciences (IB-USP) at the University of Sao Paulo, Brazil, and developed a technology for reconstructing and producing the liver in the laboratory.

A proof-of-concept study was conducted using rat liver. In the next phase of their research, scientists will adapt techniques for the production of human liver in the future to increase the supply of these organs for transplantation.

The study was supported by FAPESP Reported in the article Release To Materials Science and Engineering: C.. “The plan is to produce human liver to scale in the laboratory, which eliminates the need to wait long hours for compatible donors and reduces the risk of rejection of transplanted organs. ” Luis Carlos de Cares-Junior, The first author of the article told Agência FAPESP. He is a postdoctoral fellow at HUG-CELL, one of the Centers for Research, Innovation and Dissemination (RIDC) Funded by FAPESP.

This methodology is based on tissue bioengineering techniques recently developed to produce organs for decellularization, recellularization, and transplantation. The deceased donor’s organ, in this case the liver, is treated with various solutions containing detergents or enzymes to remove all cells from the tissue, leaving only the extracellular matrix of the organ’s original structure and shape. .. The extracellular matrix is ​​then seeded with cells from the patient. This technique avoids the risk of immune system reactions and long-term rejection.

“It is comparable to transplanting a” readjusted “liver. Because it uses the patient’s own cells, it is not rejected and there is no need to administer immunosuppressants. ” Mayana That’s, HUG-CELL Principal Investigator and Last Author of the Article.

This technique can also be used to reconstruct organs that are considered non-transplantable at the border, increasing the supply of organs to patients on the waiting list, Caires-Júnior explained.

“Many of the organs available for transplantation aren’t really available because the donor died in a car accident. Depending on the condition, this technique can be used to repair,” he said.

However, the decellularization process removes the main components of the extracellular matrix, such as the molecules that direct cells to proliferate and form blood vessels. This weakens cell adhesion to the extracellular matrix and jeopardizes recellularization.

To overcome this obstacle, HUG-CELL researchers have strengthened their technology by introducing an extra step between decellularization and recellularization.

After the rat liver was isolated and decellularized, a solution rich in molecules such as SPARC and TGFB1, which are proteins produced by hepatocytes grown in a conditioned medium in the laboratory, was injected into the extracellular matrix. These proteins are essential for a healthy liver because they direct liver cells to proliferate and form blood vessels.

“Concentrating the extracellular matrix with these molecules makes it very similar to the extracellular matrix of a healthy liver,” says Caires-Júnior.

The rat liver extracellular matrix was treated with solution and hepatocytes, endothelial cells, and mesenchymal cells were introduced into the material. Mesenchymal cells become human induced pluripotent stem cells (iPSCs) generated by reprogramming adult skin cells (or cells from other readily accessible tissues) into an embryonic pluripotent state. It comes from.

“This study shows that it is possible to induce the differentiation of human stem cells in cell lines that are part of the liver and use these cells to reconstruct and function organs. It’s a proof of concept and the first demonstration that this technique works, “said Zatz.

Hepatocytes were injected into the extracellular matrix of rat liver with a syringe pump to create an organ with human characteristics. I grew up in an incubator that simulated the condition of the human body for 5 weeks. Analysis showed that extracellular matrix enrichment by SPARC and TGFB1 significantly improved recellularization.

“This treatment has made hepatocytes grow and function more actively,” says Caires-Júnior. “We plan to build bioreactors for decellularizing the human liver and study the potential for production in the laboratory to scale them.”

He added that the technique can be adapted to create other organs such as the lungs, heart, and skin.

Organ factory

This project is one of the research lines HUG-CELL is pursuing to manufacture or reconstruct transplanted organs using a variety of techniques.

Through business Conducted in partnership with the pharmaceutical company EMS, with the support of FAPESP (Sao Paulo Research Foundation), a research partnership for technological innovation programs (PITE), HUG-CELL researchers aim to modify porcine organs such as kidneys, heart, and skin for transplantation into humans (see for details).

Pig liver is rejected when transplanted into humans, so researchers pursue other strategies such as 3D printing (see for details), decellularization, and recellularization. doing.

“These are complementary approaches. We expect to see transplant organ factories in the future,” says Zatz.

About the Sao Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) has a mission to support scientific research in all areas of knowledge by awarding scholarships, fellowships and grants to researchers associated with higher education and research institutions in the state of São Paulo, Brazil. It is a public institution to do. FAPESP recognizes that the best research can only be done in collaboration with the best international researchers. Therefore, we will establish partnerships with other countries’ funding agencies, higher education, private companies and research institutes known for their quality of research, and encourage funded scientists to further develop international cooperation. I have done it. For more information on FAPESP, please visit the following URL: http: // /en Visit FAPESP News Agency at http: // /en To keep the latest scientific progress up-to-date, FAPESP supports achievement through numerous programs, awards and research centers. You can also subscribe to FAPESP News Agency. http: // /Apply..


Researchers develop technology to produce transplantable liver in the laboratory Researchers develop technology to produce transplantable liver in the laboratory