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A technique to produce transplantable livers in the laboratory

Publicado em 06 abril 2021

Researchers at the Human Genome and Stem Cell Research Center (HUG-CELL), sponsored by the Institute of Biological Sciences (IB-USP) at the University of Sao Paulo, Brazil, have developed a technique for reconstructing and producing 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.

This study is supported by FAPESP and 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.” The article told Agência FAPESP. He is a postdoctoral fellow at HUG-CELL, one of the FAPESP-funded Research, Innovation and Dissemination Centers (RIDCs).

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.

“This is comparable to a” readjusted “liver transplant. It is not rejected because it uses the patient’s own cells and does not require the administration of immunosuppressants, “said Mayana Thatz, HUG-CELL’s lead researcher 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 transplantable organs aren’t really available because the donor died in a car accident. This technique can be used for repair in some conditions,” 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 of how this technology works, “says Thatz. ..

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 Concentration with SPARC and TGFB1 significantly improved decellularization.

“Treatment liver cell “We plan to build bioreactors for decellularizing the human liver and study the possibility of scaling them up in the laboratory,” said Caires-Júnior.

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.

HUG-CELL researchers have partnered with the pharmaceutical company EMS to support pig organs such as the kidneys and heart through a project carried out by FAPESP (San Paulo Research Foundation) with the support of the Research Partnership of the Innovation Program (PITE). I am aiming for modification. And the skin for transplantation to humans.

Because pig liver is rejected when transplanted into humans, researchers are pursuing other strategies, such as 3D printing, as well as decellularization and recellularization.

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

Laboratory-grown “mini bile ducts” first used in regenerative medicine to repair the human liver

For more information:
LuizCarlosCaires-Júnioretal, precoating decellularized liver with HepG2 conditioned medium improves liver recellularization. Materials Science and Engineering: C (2021). DOI: 10.1016 / j.msec.2020.111862

Quote: Laboratory technology for producing transplantable liver (April 6, 2021) from https: // April 2021 Obtained on the 6th.

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