Scientists have succeeded in growing kidney tissue containing predominantly human cells in pig embryos. To do this, they switched off two genes in the embryos that are important for kidney development. Kidney tissue made from human stem cells could then grow into this organ gap. Organs grown in this way could later become donor organs. The group led by Liangxue Lai from the Guangzhou Institutes of Biomedicine and Health in Guangzhou (China) presents their approach 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 explained. The problem is the same as with organ donations when donor and recipient are not a good match: then the organ is rejected by the recipient’s body because the immune system recognizes it as foreign tissue and initiates defensive measures. In addition, the pig cells in the embryo can hold their own better than human cells and both cell types have different needs in order to thrive.
Using the Crispr/Cas gene scissors, the researchers removed the genes SIX1 and SALL1, which are necessary for the development of kidneys, from a single-cell pig embryo. As a result, the embryo did not develop pig kidneys and an empty space or niche was created. Human pluripotent stem cells derived from umbilical cord blood, which can give rise to all types of human cells, were injected into the embryo. They were able to develop into kidney tissue largely without competition in the niche created.
Specially prepared human stem cells
The human stem cells had previously been specially prepared. On the one hand, genetic engineering intervention led to increased activation of the MYCN and BCL2 genes. Both genes ensure better cell survival, in the case of BCL2 by preventing programmed cell death (apoptosis). On the other hand, the researchers placed the stem cells in a recently developed culture medium (4CL), which causes the stem cells to be transferred to earlier stages of development; they then resemble early human embryonic cells.
The scientists implanted the pig embryos into sows, where they were allowed to develop until the 25th or 28th day. There were some embryos in which a kidney composed of predominantly human cells developed normally compared to untreated pig embryos. However, the process still needs improvement: “The overall proportion of degenerating pig embryos is high, and it needs to be assessed whether this is partly related to chimerism or other aspects of the injection procedure,” write the study authors.
Even the well-grown kidneys still contain more than a third of pig cells, which can lead to defense reactions in the human organism when an organ is transplanted. “Since organs are not made up of just a single cell line, we would probably have to manipulate the pigs in a much more complex way to get an organ in which everything is human-derived,” said co-author Miguel Esteban from the Guangzhou Institutes of Biomedicine and Health.
Cord blood as the basis of human stem cells
In his assessment of the study, medical ethicist Wolfram Henn from the German Ethics Council positively emphasizes that umbilical cord blood was used as the basis for the human stem cells. This avoids the use of human embryos. The procedure also offers the prospect that in the future, a patient’s own blood stem cells who are dependent on a donor organ could be used as a basis for growing the organ. Because the cells used would then come from the patient himself, there should usually be no rejection reactions. Overall, he judges the researchers’ actions to be sensible and responsible.
Henn also considers the process to be ethically justifiable with regard to animal protection: “We breed animals to eat them, so it is not reprehensible to breed animals to save human lives.” Henn believes it is particularly important that German law is modernized, as the Embryo Protection Act is now more than 30 years old. Many of the procedures used today did not exist back then, so the legal basis for research such as that described in the study had to be revised, demanded the medical ethicist.
