2023-09-09 10:23:42
After the recent world first transplant of a pig kidney into a human, Chinese researchers have succeeded in developing half-human kidneys in an animal embryo. Some elements of explanation on the new bioengineering technique.
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To respond to the organ shortage, scientists are working on xenograftsxenografts, these organ transplants from an animal to humans. They recently achieved the feat of transplanting genetically modified pig kidneys into humans. Now, it is the turn of Chinese researchers from the Guangzhou Institute of Biomedicine and Health to take up this challenge, but in the other direction. For the first time, they grew kidneys containing human and porcine cells in pig embryos. The study published in Cell Stem Cell reports that it is still far too early to exploit them for kidney transplants.
A half-humanized organ in a pig
The kidneys were chosen because they are the most commonly transplanted organ in human medicine and also the fastest to develop. Although previous studies have used similar methods to generate blood or muscle in pigs, this is the first time scientists have successfully grown a solid humanized organ in another species. After 28 days, the kidneys have reached mesonephros, the second stage of normal kidney development. For Dusko Ilicprofessor of stem cell sciencesstem cells at King’s College From london, ” this study describes the founding steps of a new approach in organ bioengineering using pigs as an incubator for the growth of human organs ».
However, this “revolutionary” solution faces numerous difficulties such as competition between human cells and pig cells. ” We worked on mechanisms to overcome the extremely low efficiency of cross-species chimeras », explain author Guangjin Pan, of the Guangzhou Institutes of Biomedicine and Health. ” We identified some critical factors that promote the formation of interspecies chimeras by facilitating cell competition ».
To overcome these difficulties, the researchers began by creating a “niche” inside a single-celled pig embryo, using CRISPRCRISPR to genetically modify this embryo so that it lacked two genes necessary for the development of kidneys. They then modified human pluripotent stem cells – those that develop into whatever you want – to facilitate their integration, and converted these cells into early human embryonic cells.
Organ transplantation is not for tomorrow
No less than 1,820 embryos were transferred to animal surrogate mothers. The scientists then took five embryos for analysis (28 days maximum following implantation) and found that they had kidneys of normal structure for their stage of development. These embryos were composed of 50 to 60% human cells.
The long-term goal is to optimize this technology for human organ transplantation, but this work might take many years. ” Since organs are not composed of a single cell lineage, to obtain an organ with all cells derived from humans we would probably have to design pigs in a much more complex way, which would pose additional problems », explains Miguel A. Esteban. In the meantime, this technology might be used to study human organ development and associated diseases.
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