Humanized kidneys developed inside pig embryos

A team of scientists 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 stage of development.

The so-called chimera embryos contain cells of two species, in this case human and pig, and are the direction of research into the still distant possibility of creating human organs in other animals for transplantation.

Chinese researchers publish these results in Journal of Cell Stem Cell, who points out that this is the first time a “humanized solid organ” has been grown in another species, although similar methods have been used to create human tissues such as blood or skeletal muscle in pigs.

The team, headed by Institutes of Biomedicine and Health Guangzhou (China), He successfully created these chimeric embryos and transferred them to sows, where the developing humanized kidneys showed normal structure and tubule formation after 28 days.

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 have been produced in mice and vice versa, but attempts to grow human organs in pigs have been unsuccessful.

The Chinese team tested an approach that improves the integration of human cells, Liangxue La, the study’s coordinator, explained to the journal.

The first step was to create a “niche” inside the pig embryo so that the human cells would not have to compete with the pig cells.

To do this, they used the gene-editing tool CRISPR, with which they designed a one-cell pig embryo that lacked two genes necessary for kidney development.

They then engineered human pluripotent stem cells (which have the potential to become any type of cell) to be more amenable to integration.

Before implanting the developing embryos into sows, the researchers grew the chimeras in conditions optimized to provide unique nutrients and signals to human and pig cells, as they often have different needs.

The scientists transferred 1,820 embryos to 13 animals and after a period of between 25 and 28 days they terminated the pregnancy and removed the embryos to assess whether the chimeras were able to produce humanized kidneys.

Five chimeric embryos were analyzed (two at 25 days post-implantation and three at 28 days) in which the humanized kidneys were “structurally normal for their stage of development and were composed of 50-60% human cells,” the note added.

The kidneys were in mesonephros stage (second stage of kidney development); they formed tubules and cell buds that would eventually become the ureters that connect the kidney to the bladder.

The team went on to investigate whether human cells are present in other tissues of the embryo, which could have ethical implications, particularly if an abundance of human cells are found in the neural or germinal tissues and the pigs go to term.

However human cells they were primarily located in the kidneys, while the rest of the embryo was made up of pig cells.

“If a niche is created in a pig embryo, human cells naturally end up in these spaces”explained the lead author, Zhen Dai, from the Guangzhou Institute of Biomedicine and Health.

The researcher said they saw “very few” human nerve cells in the brain and spinal cord and “nothing” in the genital ridge, indicating that “human pluripotent stem cells have not differentiated into germ cells.”

This work contributes to “an important advance in one of the ways that has generated the most interest in recent years” to develop a model for the production of organs suitable for transplantation using pigs as a vehicle, according to Spanish nephrologist Rafael Matesanzo, who was unaware of the study.

He is the creator National Transplant Organization, according to the Science Media Center (a platform that offers scientific sources to journalists), recalled pioneering research on Spanish scientist Juan Carlos Izpisúawhich showed the possibility of hybridization between the two species.

A Chinese research team now wants to allow humanized kidneys to develop longer and work to create other human organs in pigs, such as hearts and pancreases.

While the long-term goal is to optimize this technology for human organ transplants, the team acknowledges that the work will be complex and could take many years.

Growing a fully functional humanized organ in a pig would require several 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 the cells, meaning that the kidneys had vascular cells derived from pigs, and this could lead to organ rejection if used in a transplant scenario, so there is still a lot of research needed.

Currently, this technology, according to Miguel Esteban of the Guangzhou Institute of Biomedicine and Health, also a signatory, “provides a window to study human development” and developmental diseases.