Human kidney tissue grows in pig embryos

Scientists have grown kidney tissue containing mainly human cells in pig embryos. Organs grown in this way can later become donor organs.

To do this, the researchers switched off two genes in the pig embryos that are important for kidney development. Kidney tissue from human stem cells could then grow into this organ opening. The group led by Liangxue Lai of the Institutes of Biomedicine and Health in Guangzhou (China) presented their approach Thursday in the journal Cell Stem Cell.

“Rat organs have been produced in mice and mouse organs in rats, but previous attempts to grow human organs in pigs have been unsuccessful,” Lai explains. The problem is the same as with organ donation, where donor and recipient are not a good match: the recipient’s body then rejects the organ because the immune system recognizes it as foreign tissue and initiates defensive measures. In addition, the pig cells in the embryo can survive better than the human cells and both cell types have different needs to thrive.

Stem cells from umbilical cord blood Using the Crispr/Cas gene scissors, the researchers removed the genes SIX1 and SALL1, which are necessary for the development of the kidneys, from a single-cell pig embryo. As a result, the embryo did not develop pig kidneys, a vacancy or niche was created. Human pluripotent stem cells derived from umbilical cord blood, which can give rise to all kinds of human cells, were injected into the embryo. In the created niche, they could develop into kidney tissue largely without competition.

The human stem cells were specially prepared beforehand. On the one hand, genetic manipulation caused the MYCN and BCL2 genes to become increasingly activated. Both genes ensure better cell survival, in the case of BCL2 by preventing programmed cell death (apoptosis). Second, the researchers placed the stem cells in a recently developed nutrient medium (4CL) that allows the stem cells to be transferred to earlier stages of development; they then resemble early human embryonic cells.

The scientists planted the pig embryos in sows, where they were allowed to develop until day 25 or 28. There were some embryos in which a kidney composed mainly of human cells had developed normally compared to untreated pig embryos. However, the procedure still needs improvement: “The overall proportion of degenerating pig embryos is high and it needs to be assessed whether this is partially related to chimerism or other aspects of the injection procedure,” the study authors write.

Even the well-developed kidneys still contain over a third of the cells of pigs, which can lead to immune reactions in the human organism during organ transplantation. Co-author Miguel Esteban of the Guangzhou Institutes of Biomedicine and Health says:

Medical ethicist Wolfram Henn of the German Ethics Council positively emphasizes in his assessment of the study that umbilical cord blood was used as the basis for human stem cells. This avoids the use of human embryos. The procedure also offers the prospect of using the blood stem cells of a patient who is dependent on a donor organ as the basis for culturing the organ. Because the cells used then come from the patient himself, rejection reactions should not usually occur. Overall, he considers the approach of the researchers reasonable and responsible.

Henn also considers the process ethical in terms of animal welfare: “We breed animals to eat them, so it is not objectionable to breed animals to save human lives.” Henn believes it is particularly important to modernize German legislation, as the Embryo Protection Act is now over thirty years old. Many of the current procedures did not exist at the time, so that the legal basis for research as described in the study had to be revised, the medical ethicist demanded.

(yam/sda/dpa)