2023-09-07 21:10:50
A team of scientists has developed, for the first time, pig embryos whose kidneys contained 50–60% human cells and which, after 28 days of gestation in that animal, showed a normal structure for its development phase.
The figure shows humanized kidney cells (red fluorescence) within the embryo compared to an entirely porcine embryo. Credit: Wang, Xie, Li, Li, and Zhang et al./Cell Stem Cell.
The so-called chimera embryos contain cells from two species, in this case human and pig, and are a line of research into the still distant possibility of generating human organs in other animals for transplants. They are humanized kidneys inside pig embryos.
Chinese researchers publish these results in the journal Cell Stem Cell, which points out that it is the first time that it has been possible to cultivate a “humanized solid organ” in another species, although similar methods have been used to generate human tissues such as blood or skeletal muscle. in pigs.
The team, led by the Institutes of Biomedicine and Health in Guangzhou, China, successfully created these chimeric embryos and transferred them to sows, where the developing humanized kidneys had normal structure and tubule formation after 28 days.
The researchers focused on kidneys because they are one of the first organs to develop and are also the most transplanted in human medicine.
Until now, rat organs had been grown in mice and vice versa, but attempts to grow human organs in pigs had not been successful.
The Chinese team tested an approach that improves the integration of human cells, Liangxue La, coordinator of the study, explained to the magazine.
The first step was to create a “niche” within the pig embryo so that human cells would not have to compete with pig cells.
To do this, they used the CRISPR gene editing tool, with which they designed a single-cell porcine embryo that was missing two genes necessary for kidney development.
They then engineered human pluripotent stem cells (which have the potential to become any type of cell) to make them more susceptible to integration.
Before implanting the developing embryos into the sows, the researchers grew the chimeras under conditions optimized to provide unique nutrients and signals to both human and pig cells, as they often have disparate needs.
Humanized kidneys
The researchers transferred 1,820 embryos to 13 animals and after a period of between 25 or 28 days, they interrupted the gestation and extracted the embryos to evaluate whether the chimeras had managed to produce humanized kidneys.
Five chimeric embryos were analyzed (two 25 days after implantation and three 28 days old) in which the humanized kidneys were “structurally normal for their development phase and were composed of 50-60% human cells,” the note adds. .
The kidneys were in the mesonephros stage (the second stage of kidney development); they had formed tubules and cell buds that would eventually become ureters connecting the kidney to the bladder.
The team also investigated whether there were human cells in other tissues of the embryos, which could have ethical implications, especially if abundant human cells were found in neural or germline tissues and the pigs were carried to term.
However, the human cells were located, above all, in the kidneys, while the rest of the embryo was made up of porcine cells.
“If a niche is created in the pig embryo, human cells will naturally end up in those spaces,” explained lead author Zhen Dai, from the Guangzhou Institute of Biomedicine and Health.
The researcher assured that they saw “very few” human neuronal cells in the brain and spinal cord and “none” in the genital ridge, indicating that “human pluripotent stem cells did not differentiate into germ cells.”
Matesanz and Izpisúa
This work provides “important advances in one of the ways that has aroused the most interest in recent years” to develop a model for the production of organs suitable for transplantation through the use of pigs as a vehicle animal, in the opinion of the Spanish nephrologist Rafael Matesanz, oblivious to the study.
The creator of the National Transplant Organizationcited by Science Media Center (a platform that offers scientific sources to journalists), recalled the pioneering research of Spanish scientist Juan Carlos Izpisúa, who demonstrated the possibility of hybridization between two species.
The team of Chinese researchers now wants to allow the humanized kidneys to develop for longer and are working to generate other human organs in pigs, such as the heart and pancreas.
Although the long-term goal is to optimize this technology for human organ transplantation, the team recognizes that the work will be complex and could take many years.
Growing a fully functional humanized organ in a pig would require some additional steps because organs are made up of multiple types of cells and tissues.
In this study, the researchers created a niche for only a subset of cells, meaning the kidneys had vascular cells derived from pigs, and this could lead to organ rejection if they were used in a transplant scenario, so they still a lot of research is needed.
For the moment, this technology, according to fellow signatory Miguel Esteban of the Guangzhou Institute of Biomedicine and Health, “provides a window to study human development” and developmental diseases.
The figure shows humanized kidney cells (red fluorescence) within the embryo compared to an entirely porcine embryo. Credit: Wang, Xie, Li, Li, and Zhang et al./Cell Stem Cell.
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