Scientists have succeeded in growing a human organ inside another animal for the first time.
In a new study published Thursday (September 7) in the journal Stem cellResearchers inserted human stem cells into genetically modified pig embryos. When transplanted into surrogate pig mothers, the embryos developed early-stage human kidneys within about 28 days.
The research is still in its early stages, but the authors say the technology could one day help alleviate the shortage of human organs needed for transplants.
“Murine organs have been produced in mice, and mouse organs have been produced in mice, but previous attempts to transplant human organs into pigs have not been successful,” said Liangxue Lai, senior author of the study and a principal investigator at the Guangzhou Institutes of Biomedicine and Health. The Chinese Academy of Sciences and Wuyi University said in a statement.
In previous experiments, scientists Harvested pig kidneys And hearts From genetically modified pigs and transplanting them into brain-dead organ donors, this strategy comes with a high risk of the human body rejecting the pig organs. The new research aims to reduce this problem.
“Our approach improves the incorporation of human cells into recipient tissues and allows us to grow human organs in pigs,” Lai said.
Related: Most lab-grown human embryo models look like the real thing
The kidneys are two bean-shaped organs located on either side of the spine, below the rib cage, that filter blood and remove waste and excess water through urine. They are among The most common transplanted organsbut a shortage of available kidneys means there’s a growing list of people who need one — for example, in the neighborhood 100,000 people in the United States They were on the waiting list for a kidney in 2020, but only 23,000 got one.
One solution is human integration Stem Cells That can develop into any type of cell, called induced pluripotent stem cells (iPSCs), are transferred to other mammalian embryos to create “mixed” or “chimeric” embryos that can grow human organs. Pigs are a good choice for this purpose because… Our organs are similar to our organs And so they are Embryonic development. However, the challenge is that the pig cells in the fetus can easily outcompete human cells and require different nutrients and chemical signals to grow.
In the new study, the researchers overcame these challenges using… CRISPR Technology to inactivate two genes that would enable fetal pig cells to develop kidneys. This created a “niche” for human iPSCs to fill. The researchers also manipulated the human iPSCs so that they were more likely to integrate with pig cells by matching their developmental stage. Without this modification, human cells would outgrow their pig counterparts. Science mentioned.
The team implanted 1,820 chimeric embryos into 13 surrogate pig mothers, then terminated the pregnancy and extracted the embryos about a month later. Of these embryos, five contained early-stage kidneys composed of about 50% to 60% human cells and were “structurally normal” for this stage of development. They contain the cells that will eventually become UreterThe tube-like structures that connect the kidneys to the bladder.
Related: How long can organs remain outside the body before being transplanted?
Most importantly, the scientists confirmed that the human cells in the fetus were mainly located in the kidneys, and not in other fetal tissues, such as Sex or nerve Cells that could raise ethical questions if allowed to reach maturity in piglets.
This technology is still far from being applied to human organ transplantation. One crucial hurdle is the issue of immune rejection, as the kidneys created by the team still contain pig-derived cells, such as those that form blood vessels. A large number of pig embryos also ended up deteriorating in the study, so the efficiency of the process will need to be addressed by future research.
In the meantime, the team hopes the findings will improve our understanding of human organ development and developmental diseases.
“Before we get to that late stage of making organs that could be shelved for clinical practice, this method provides a window into studying human development.” Miguel EstebanA co-author of the study and a principal investigator at the Guangzhou Institutes of Biomedicine and Health said in the statement. “You can track the human cells you inject and manipulate them so you can study diseases and how cell lineages are shaped.”