Rats with mouse kidneys
For patients with the last stages of renal insufficiency, the only hope for restoring the quality of life is kidney transplantation. However, due to the chronic shortage of donor organs, many of these patients do not survive to a life-saving operation.
In recent years, researchers have been actively working on developing methods for growing healthy organs outside the human body. One of these methods, known as blastocyst complementation, is already showing promising results. Scientists isolate blastocysts – clusters of cells formed a few days after fertilization – mutant animals that do not have specific organs, and inject them with stem cells from a normal donor, not necessarily of the same species. After that, the stem cells differentiate and form the missing organ in the developing animal's body. The resulting organ retains the characteristics of a stem cell donor and is potentially suitable for transplantation.
Initially, Japanese researchers from the National Institute of Physiological Sciences used the blastocyst complementation method to grow rat pancreas in the body of mutant mice that do not have this organ. Subsequently, they decided to try to adapt this method for growing functional kidneys, which, due to the large shortage of donor organs, would bring much more benefits in the field of regenerative medicine.
The first attempts to grow rat kidneys in mice were unsuccessful, since rat stem cells did not differentiate into the two main types of cells necessary for kidney formation. However, in the opposite scenario, mouse stem cells effectively differentiated and formed the basic kidney structures inside rat blastocysts that were unable to form their own kidneys due to a defect in the Sall1 gene.
After implantation to pseudo-pregnant rats, the complementary blastocysts matured into normal embryos. It is important to note that more than two-thirds of the cubs born as a result had a pair of kidneys formed from mouse stem cells. Further screening demonstrated the structural integrity of the kidneys, at least half of which potentially had the ability to produce urine. Unfortunately, all chimera rats died quickly due to the inability to suck milk due to congenital anosmia (lack of sense of smell). The researchers believe that in the future this problem can be avoided by inactivating another gene necessary for kidney formation.
According to the authors, the results of their work confirm that interspecific complementation of blastocysts is a viable method of obtaining functional kidneys. Perhaps in the future this approach will be adapted for growing human kidneys from stem cells in animal organisms. This will prolong life and improve its quality for millions of people around the world.
Article by Teppei Goto et al. Generation of pluripotent stem cell-derived mouse kidneys in Sall1-targeted anephric rats published in the journal Nature Communications.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru Based on the materials of the National Institute for Physiological Sciences: Researchers One Step Closer to Growing Made-to-Order Human Kids.