Another step towards creating a bioengineered kidney

"Minipochka" is grown in the laboratory

Alexandra Bruter, Polit.<url> based on the materials of the Salk Institute for Biological Studies:
Salk scientists for the first time generate "mini-kidney" structures from human stem cellsAn international group of scientists from Spain and the USA managed to create small, kidney-like structures in laboratory conditions using induced pluripotent stem (iPS) cells.

Not all kidney diseases respond well to treatment, the ability of the kidneys to regenerate is generally very low. Therefore, hemodialysis (as a supportive measure) and kidney transplantation are often the only ways to help the patient. All these are expensive and complex procedures that reduce the quality of life.

The creation of artificial organs seems to be a promising, albeit complex, area of medicine. On the way to an artificial organ, two main tasks must be solved. First, you need to get the cells that the organ should consist of. Secondly, the cells must be "persuaded" to form an appropriate three-dimensional structure.

Cells of the desired type can be obtained from embryonic stem cells. In recent years, scientists have managed to select cultivation conditions, low molecular weight substances or proteins that cause the transformation of stem cells into cells of this type for some types of cells. But usually scientists have nowhere to take embryonic stem cells of an adult patient, because he was an embryo a long time ago.

Here, a discovery that was awarded the Nobel Prize in 2012 comes to the aid of scientists. Shinya Yamanaka showed that if four genes that work in the early stages of development are made to work in the most ordinary skin cells, then the cells will become very similar in their properties to embryonic stem cells. Such cells are called induced pluripotent stem cells. Now you can take ordinary somatic cells, activate several genes in them and get iPS cells. Then in a certain way to influence these cells, and get the cells of the desired type. This process is called differentiation. It turns out that somatic cells of a certain type can be obtained from somatic cells of another type. It cannot be said that science is able to do everything in this area, but certain successes have been achieved. However, so far the progress in obtaining kidney cells has been quite modest.

Things are even more complicated with the formation of the desired three-dimensional structure. So far, it is possible to reproduce only the simplest structures, for example, papillae of the dermis. The structure of the kidney is very complex, and its formation process during embryonic development is multi-stage and includes a large number of interactions of cells of different types.

The authors of the described work, published in the journal Nature Cell Biology (Yun Xia et al., Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells), managed to significantly advance the solution of both problems.

First, they developed a two-stage scheme for producing cells similar to the immediate precursors of mature kidney cells. At the first stage, embryonic stem cells differentiate into mesoderm cells – one of the three germ leaves from which connective tissue, muscles, and some blood and kidney cells are formed in the embryo. To do this, two proteins were activated in the cells. At the next stage, with the help of retinoic acid, a protein complex called activin A that plays a role in a variety of processes occurring in the body, and the BMP2 protein that regulates mesoderm differentiation, more differentiated cells similar to kidney cells were obtained. Most of all, the resulting cells resembled the cells of the rudiment of the ureter.

Simplistically, one of the final stages of kidney development in mammals occurs as follows. From the side of the cloaca towards the skull, the rudiment of the future ureter begins to grow. When it grows to the mesoderm located on the site of the future kidney, it begins to branch, forming a system of renal tubules. In addition, during this interaction, a renal pelvis is formed, as well as large and small renal cups.

By mixing the reprogrammed cells with a small number of mouse embryonic kidney cells, the authors found that the cells formed a three-dimensional structure similar to an embryonic ureter. This three-dimensional structure was able, interacting with mesodermal cells, to launch processes similar to those described above.

Thus, the scientists managed to take several steps on the way to growing an artificial kidney. But an artificial kidney is still far away, and the results of the work can be applied now. Having obtained iPS cells from the cells of a person suffering from some kind of kidney disease, such an artificial "minipochka" can be used to test potential drugs for this disease. The authors even performed all of the above manipulations with the cells of a patient with a hereditary disease – polycystic kidney disease.

Portal "Eternal youth" http://vechnayamolodost.ru19.11.2013