09 January 2014

Cellular technologies: will be done and is already being done

Reprogrammed cells and new organs

Maxim Russo, <url>A little more than a year has passed since the Japanese scientist Shinya Yamanaka was named one of the laureates of the Nobel Prize in Physiology and Medicine in November 2012, and the term "induced pluripotent stem cells" (iPS cells) moved from the pages of special scientific journals to mass publications.

Over the past time, the intensity of research in the field of the use of stem cells for medical purposes has not decreased at all.

Let us briefly recall the essence of the case. Stem cells are progenitor cells that are able to turn into cells of other types (differentiate) during the division process. This makes them extremely valuable for the treatment of many diseases, including oncological and neurodegenerative, the restoration of damaged organs and tissues, for example, the heart muscle after a heart attack. Theoretically, it is even possible to grow a new organ. However, getting stem cells is not so easy. Toti-content (which can differentiate into anything) stem cells make up the body of an embryo in the early stages of development. In the adult body, there are stem cells whose ability to differentiate is limited. Their main sources are bone marrow and adipose tissue. But a stem cell from the bone marrow can turn into a blood cell, but it will not give new nerve cells.

Embryonic stem cells are also not all right. Foreign stem cells will cause an immune response in the patient. And the laws of a number of countries prohibit or restrict the use of human embryo tissues for medical purposes. A person's own embryonic stem cells can be obtained at birth from umbilical cord blood,

It was from this situation that Shinya Yamanaka found a way out. In August 2006, he published an article in the journal Cell, in which he described an experiment on the transformation of ordinary mouse cells into stem cells. In the summer of the following year, the next stage of the experiments was described in Nature. In November 2007, Yamanaka and his colleagues obtained stem cells from human fibroblast cells.

The essence of the Yamanaki method is to introduce certain genes into the cell genome. Once, when the cell was a stem cell, these genes were already working in the cell, but in the process of differentiation they turned off. If these same genes are artificially introduced into the genome by creating a special virus, they will start working, and soon similar genes of the cell itself will "wake up". As a result, they force (induce) the somatic cell to turn into a stem cell. This process is now often called cell reprogramming. The enormous potential of Yamanaki's discovery forced the Nobel Committee to award him the prize urgently, less than six years after the discovery (often decades pass from discovery to award) and at a relatively young age – 50 years (the average age of laureates in the field of physiology and medicine is 58 years).

Active work with iPS cells began after Yamanaka's first publications, in 2013 the intensity of research did not decrease at all. Scientists are striving to create new organs from cells, but if certain successes have already been achieved in the differentiation of cells, then it is much more difficult to force cells to form the necessary three-dimensional structure, turning, for example, into a liver or kidney. But even here, in the outgoing year, progress was noticeable. A group of scientists from Barcelona and California were able to create kidney-like structures from induced stem cells. At Columbia University, lung tissue was created from induced and embryonic stem cells. Japanese scientists were not only able to grow a similar liver from mouse iPS cells, but also successfully transplant this liver into the body of mice.

Among the works on organ cultivation, an interesting attempt by English doctors to grow artificial teeth using adult gum cells and mouse mesenchymal stem cells. A similar result was achieved by Chinese scientists who obtained sections of dental tissue from iPS cells.

In Copenhagen, a group engaged in growing pancreatic tissue achieved success. Scientists obtained progenitor cells of the right type and managed to grow a miniature organoid, where there was even a network of islands similar to that of a real gland. An organoid existing in a gel medium was able to produce digestive enzymes or hormones, such as insulin. Such organoids cannot yet be transplanted into the patient's body, but they can already be used to test drugs for diseases of the corresponding organ. At the Institute of Molecular Biology in Austria, even an organoid was grown in a similar way from human brain tissue.

But scientists from Tokyo, who are engaged in growing lacrimal and salivary glands from stem cells, have already been able to transplant the received organs to patients. However, while mice act as patients. The glands had been working successfully for 18 months at the time of publication of the study results – a very long time for a mouse. This study will help in the future in the treatment of xerophthalmia – dryness of the cornea of the eye due to the cessation of the lacrimal glands.

In Boston, they managed to transplant artificially created kidneys to mice. In one case, scientists applied the technology of the so-called "cell-free matrix". The matrix is the framework of any organ surrounding each cell. Now a method has been developed to wash out all cells from the matrix, leaving the skeleton itself intact. What is most surprising, then this framework can be repopulated with cells of the appropriate type and get an organ again. Such kidneys were transplanted to mice in the experiment. They worked less efficiently than usual, but still performed their functions. Cell-free matrix technology is now very promising in transplantology, because it allows the patient to give a new organ from his own cells (derived from iPS cells) and thereby avoid immune rejection.

An impressive experiment using this method was conducted in 2013 in Pittsburgh. Scientists have obtained a mouse heart matrix, and populated it with human cells-precursors of cardiovascular tissue cells. The cells were obtained by reprogramming skin cells into iPS cells. As a result, the heart tissues recovered and even began to contract spontaneously, reaching 50 beats per minute.

With the help of cell reprogramming, scientists from the University of Minnesota have developed a method for treating Duchenne myodystrophy, a disease that is considered incurable so far. It is associated with a point mutation that blocks the synthesis of the protein dystrophin. The experiment was conducted on mice. The researchers took the skin cells of these mice, reprogrammed them into pluripotent stem cells, then, using a specially created mobile genetic element (transposon), inserted a gene encoding the missing protein into these cells. Finally, the scientists were also able to make the resulting stem cells differentiate into muscle tissue cells.

Portal "Eternal youth" http://vechnayamolodost.ru09.01.2014

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