After the world’s first transplant of a pig kidney into a human, Chinese researchers have recently succeeded in developing semi-human kidneys from an animal embryo. Some explanatory elements about the new biotechnological technology.
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To respond to the organ shortage, scientists are working on xenografts, organ transplants from animals to humans. They recently achieved the feat of transplanting genetically modified pig kidneys into humans. Now it’s the turn of Chinese researchers from the Guangzhou Institute of Biomedicine and Health to take on that challenge, but in the opposite direction. For the first time, they grew kidneys containing human and pig cells in pig embryos. The study, published in Cell Stem Cell, reports that it’s far too early to use it for kidney transplants.
A semi-humanized pig organ
The choice fell on the kidneys because they are the most frequently transplanted organ in human medicine and also develop the fastest. Although previous studies have used similar methods to generate blood or muscle in pigs, this is the first time scientists have succeeded in growing a solid humanized organ in another species. After 28 days, the kidneys have reached mesonephros, the second stage of normal kidney development. For Dusko Ilic, Professor of Stem Cell Science at King’s College London, “This study describes the basic steps of a new approach to organ bioengineering, using pigs as incubators for the growth of human organs.”
However, this “revolutionary” solution faces numerous difficulties, such as the competition between human cells and pig cells. “We have been working on mechanisms to overcome the extremely low efficiency of cross-species chimeras,” says author Guangjin Pan from the Guangzhou Institutes of Biomedicine and Health. “We have identified some critical factors that promote the formation of interspecies chimeras by facilitating cell competition.”
To overcome these difficulties, the researchers first created a ‘niche’ in a single-celled pig embryo and used CRISPR to genetically alter the embryo so that it lacked two genes necessary for kidney development. They then modified human pluripotent stem cells — the kind that will develop into anything you want — to make them easier to integrate, turning those cells into early human embryonic cells.
An organ transplant is not something for tomorrow
No fewer than 1,820 embryos were transferred to animal surrogate mothers. The scientists then took five embryos for analysis (maximum 28 days after implantation) and found that they had kidneys of normal structure for their developmental stage. These embryos consisted of 50 to 60% human cells.
The long-term goal is to optimize this technology for human organ transplantation, but that work could take many years. “Since the organs do not consist of a single cell line, to get an organ with all the human cells, we would probably have to construct the pigs in a much more complex way, which would introduce additional problems,” explains Miguel A. Esteban. Meanwhile, this technology could be used to study the development of human organs and related diseases.
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