Technique that resuscitated pig cells could be used in humans in the future

posted on 08/04/2022 06:00

(credit: Anthony DeCarlo – Yale University)

When the heart stops beating, stopping blood flow, a series of reactions leads to the destruction of cells. The process is fast and, in minutes, the damage can be irreversible. However, researchers led by Yale University in the United States managed to restore the metabolism and function of vital tissues, including the heart and brain, of pigs declared dead. The technique, called OrganEx and described in the journal Nature, is a continuation of an experiment they carried out three years ago and paves the way for new treatments for medical emergencies, as well as better conservation of organs for transplants.

In 2019, researchers recovered brain cells from decapitated pigs hours earlier — they had been slaughtered for food. Neither then nor now, however, has an attempt been made to restore the organ’s electrical activity. That is, the animals were not resurrected, but the functions of their cells were. In theory, the procedure could be applied to people who have suffered a heart attack or stroke, with a considerable chance of reversing the damage caused by the interruption of oxygen flow. However, this is still a remote possibility, stressed the authors, in an online press conference.

“What is extraordinary about this study is that, in many different organs, a very large amount of functions of different cells were recovered. But I would like to emphasize that we are very far from even thinking about doing a similar study in humans”, he said. corresponding author Nenad Sestan, a neurologist at Yale. If, in the group’s first experiment, only brain cells were reactivated, it has now also been possible to recover tissue functions in the heart, kidneys, liver and pancreas.

The most likely use, according to the scientists, and also still far from the clinical point of view, is to preserve organs for the purpose of transplanting them. Organ donation can be divided into two categories: after circulatory death and after brain death. “Currently, most organ donations happen after brain death: the brainstem has ceased to function permanently, but the body is functional,” explains Anders Sandberg, a researcher at the University of Oxford, commenting on the study. “However, even in these cases, there will be a period of no circulation before artificial circulation can be instituted, and organs are likely to be damaged.”

Due to this fact and the global shortage of donors, there is great interest in preservation methods involving perfusion in oxygenated machines, which try to reduce the risk of damage and manage to improve the performance of organs already at the limit of use. An example of the technique that became known especially during the crisis of the covid-19 pandemic is extracorporeal membrane oxygenation (ECMO), equipment that promotes blood and O2 circulation of the patient, functioning as an artificial lung and heart.

electrical activity

In the current study, the team tested more advanced technology on animals that were induced to have a heart attack. One hour after death, the scientists used OrganEx, which consists of a device similar to Ecmo, combined with an experimental fluid, which contains compounds capable of promoting cellular health and preventing inflammation in all organs.

The bodies of the pigs were left for six hours under the regimen. After that time, the scientists found that cellular metabolism was active in vital tissues, such as the heart and liver, and that some organ functions had been restored. They found evidence, for example, of electrical activity in the heart, which maintained its ability to contract.

“Under the microscope, it was difficult to tell the difference between a healthy organ and one that had been treated with OrganEx technology after death,” Zvonimir Vrselja, co-author of the study, said at the press conference. The researchers also compared the technology’s performance to that of Ecmo and noted that the new approach restores a greater number of cells and functions. “In this study, we learned that cells don’t die the way we thought, opening up the possibility of, as an intervention, telling them not to die,” said Vrselja.

distant clinic

“Although the experiment was carried out in pigs, helping humans is an obvious objective, and the most obvious impact is on organ donation. The technology in the article can help overcome the risk of organ destruction, making more transplants possible,” he said. Sandberg of the University of Oxford. But despite the positive results, the scientists point out that there is still a long way to go. “We’re sorry to disappoint you, but we’re a long way from clinical use,” said Stephen R. Latham of the Interdisciplinary Center for Bioethics at Yale. “We found that, yes, it is possible to restore the metabolic function of a large chain of organs, but we have to study the degree of ischemic damage in much greater detail before attempting an experiment on a human being. And we are a long way from that.”

Still, experts are excited about the method’s future possibilities. “OrganEx could preserve organs from people who have died but whose underlying cause of death remains treatable, such as athletes who die suddenly from a heart defect, people who die from drowning or massive bleeding after a car accident,” believes Sam Parnia, professor of Intensive Care Medicine and researcher of resuscitation techniques at New York University.

“The OrganEx system can preserve these people’s organs and prevent brain damage for hours in people after death,” continues Parnia, who was not involved in the study. “This will give doctors time to correct the underlying condition, such as a blocked blood vessel in the heart that led to a massive heart attack and death, or repair a ruptured blood vessel that led to death from hemorrhage, restore organ function, and bring these people back to life many hours after death.”

Synthetic embryos created

  (credit: Weizmann Institute of Science/Disclosure)

credit: Weizmann Institute of Science/Disclosure

Researchers at the Weizmann Institute of Science in Israel developed synthetic mouse embryos outside the uterus from stem cells grown in a Petri dish — that is, without the use of fertilized eggs. The method, tested for the first time, opens new horizons for studying how these structures form organs in the developing living being and, according to the scientists, could one day lead to the creation of tissues and organs for transplantation from artificial models.

In the study, published in the journal Cell, the researchers pretreated stem cells for 48 hours to express in two types of genes: placental or yolk sac regulators. “We gave them a boost to give rise to extraembryonic tissues that support the developing embryo,” said Jacob Hanna, from Weizmann’s Department of Molecular Genetics, who led the team, in a note.

Shortly after being mixed together inside a device developed by the researchers, the cells came together in aggregates, the vast majority of which failed to develop properly. But about 0.5% (50 out of 10,000) went on to form spheres, each of which later became an elongated, embryo-like structure.

The synthetic models developed normally until day 8.5 — nearly half of the mouse’s 20-day gestation. This is the stage where all of the early organ progenitors formed, including a beating heart, circulating blood stem cells, and a brain with well-formed folds. When compared with natural mouse embryos, the artificial ones showed a similarity of 95% both in the shape of the internal structures and in the patterns of gene expression of different types of cells.

“It’s an impressive feat that can open different horizons. Many of the advances in medicine, in treatment, in knowledge, come from basic research, such as this synthetic embryo. Now, we need to follow up to see if it will really have clinical applicability”, says Hitomi Miura. Nakagawa, gynecologist and member of the Board of Directors of the Brazilian Association of Assisted Reproduction (Sbra).

The doctor recalls that, although the use of human embryonic stem cells is allowed in several countries, such as Brazil, there are ethical and ideological issues behind this issue. “Of course, there is still a long way to go. It is a first step. If you do not use stem cells from fertilized embryos, whose research results have been frustrating, it may increase society’s acceptance of future treatments arising from these initiatives. “, he observes.

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