02 July 2008

Stem cells: a review of the latest news

Alexey Levin, Voice of AmericaA new refuge

American scientists have discovered a previously unknown reservoir of specialized stem cells with the ability to transform into heart muscle cells.

Nature has endowed the heart tissues with a very complex structure. The heart is enclosed in a closed protective sac – the pericardium. The lion's share of the heart's weight falls on the myocardium, the tissues of the heart muscle. The unique ability of the myocardium to work smoothly throughout human life is provided by the special properties of its cells, cardiomyocytes. From the inside, the cardiac cavities are lined with a smooth shell, the endocardium. Outside, the myocardium is surrounded by a layer of epithelium separating it from the pericardium – this is the epicardium.

Scientists have long been extremely interested in stem cells that provide renewal of cardiac tissues. There is every reason to hope that these cells can be used to repair the heart in myocardial infarction and many other diseases. It is now known that they do not form a single family at all.

Two years ago, cardiologists from Boston Children's Hospital isolated a population of heart stem cells carrying a protein on their outer membranes that is synthesized when the Nkx2-5 gene is triggered. It turned out that they give rise to cardiomyocytes and some other cells that are part of the tissues that form the cavities of the left half of the heart. At the same time, their colleagues from the Massachusetts State Hospital proved that the same tissues of the right side of the heart are born from stem cells labeled with the Isl1 protein. Both groups of these stem cells are located in the inner regions of the heart.

Now, researchers at Harvard University and the same Boston Hospital have discovered in experiments on mice that the precursors of cardiomyocytes are hidden in the epicardium. These stem cells also possess a specific membrane marker, for the production of which the Wt1 gene is responsible. The results of William Pu and his colleagues have already been confirmed by researchers at the University of California, San Diego.

It turns out there are a lot of themThe tissues of each organ of an adult organism may contain not one, but several varieties of specialized stem cells involved in the processes of its self-repair.

Mario Capecchi, the winner of last year's Nobel Prize in Physiology or Medicine, and his colleague at the University of Utah Eugenio Sangiorgi think so. Their experiments indicate that the formation of the inner lining of the small intestine of mice most likely requires at least two varieties of stem cells.

This result contradicts the popular opinion that only a homogeneous population of identical and specific stem cells can be present in the tissues of any single organ. For example, according to this concept, all the stem cells of the functional liver tissue belong to only one specific type, and the stem cells of the heart muscle belong to another (but again, only one).

Professor Capecchi stressed that if the statement about the multiplicity of stem cells within one organ turns from a hypothesis into a reliably established fact, it will have to be taken into account in the most serious way when planning experiments on the use of stem cells for medical purposes.

Artificial neurons are on the wayResearchers from California for the first time managed to force embryonic stem cells with full guarantee to give rise to the precursors of full-fledged neurons.

Many laboratories have been trying to carry out such transformations for a long time. Such experiments not only have a purely scientific value, but can also greatly advance practical medicine.

The creation of reliable methods for converting embryonic or other stem cells into neurons of the brain and spinal cord would be the beginning of a genuine revolution in the fight against strokes, neurodegenerative diseases and traumatic injuries of the central nervous system.

The experience of recent years says that this is a very difficult task. The first problem is that embryonic stem cells can give rise not only to neurons, but also to cells of the neuroglia, the auxiliary tissue of the brain. This line of transformations should be cut off in advance, which is by no means easy. It is also necessary to ensure the survival of newborn neurons, which often die quickly. In addition, it is necessary to prevent the malignant degeneration of the descendants of stem cells, which happens not infrequently.

Employees of the Barnemovsky Institute of Medical Research and the Research Institute named after Scripps believe that they have managed to find a way to solve these problems with the help of genetic reprogramming of the original cells. In this way, Stuart Lipton and his colleagues forced the embryonic stem cells of mice to produce a protein in abundance that triggers exactly the genes they need to turn into precursors of neurons.

It is worth noting that this protein MEF2C was recently discovered and studied in the laboratory of the same prof. Lipton. With its help, scientists created a colony of precursor neurons, which they then transplanted into the brains of experimental animals, where they gave rise to normal neurons. The same experiment demonstrated that MEF2C silences the genes that cause premature death of transplants.

Researchers from Lipton's team have also shown that this technique can be used for therapeutic purposes. They planted newly created precursors of neurons in the brains of mice affected by an artificially induced stroke. Although this procedure did not lead to a complete cure of the animals, their condition improved significantly.

The stimulator moleculeScientists from Dallas have obtained synthetic molecules that trigger the formation of mature nerve tissue from stem cells preceding it.

This discovery was made thanks to a happy accident.

Molecular biologist Jenny Hsieh and her colleagues at the University of Texas Medical Center studied the possibilities of using embryonic stem cells to combat acute cardiac circulatory disorders. As part of this program, they were searching for substances that could make such cells turn into cardiomyocytes, heart muscle cells. To do this, they tested 147 thousand different compounds, hoping to find suitable biostimulants among them. Texas scientists managed to make several promising findings, which they reported in April.

However, these searches gave a completely unexpected result. The experimenters identified five compounds that did nothing to help the formation of cardiomyocytes, but instead forced stem cells to give rise to analogues of neurons. After studying their structures, they synthesized a new substance, isoxazole-9, which triggers these transformations with much greater efficiency. With its help, they have already managed to change the precursors of hippocampal cells multiplied in culture in such a way that they began to behave in many respects like mature neurons of this part of the brain.

Texas researchers claim that isoxazole-9 is among the most powerful stimulators of nerve cell growth known to science. They plan to continue studying its potential and, in particular, to test whether it can turn progenitor stem cells into full-fledged neurons. If successful, there will be hope that with the help of isoxazole-9 it will be possible to grow nerve cells for their subsequent transplantation to patients suffering from neurodegenerative diseases.

A new way to obtain stem cellsScientists from the USA and Switzerland have performed experiments that indicate the possibility of creating a new way of converting ordinary somatic cells into stem cells.

Our body is largely composed of epithelial tissue. It serves as the main component of many glands, covers the outer surface of the body and lines its hollow organs, with the exception of blood and lymphatic vessels. Epithelial cells are able to transform into cells of another type, which are called mesenchymal.

Editor's note: mesenchymal (mesenchymal, stromal) stem cells are able to differentiate into several types of cells of various organs and tissues, primarily originating from mesenchyma, germinal connective tissue. From the mesenchyme, the connective tissue itself, the endothelium of blood vessels, blood cells, muscles, skeleton, pigment cells and the lower layer of the connective tissue part of the skin are formed. Mesenchymal stem cells are found mainly in the bone marrow, as well as in adipose and bone tissues and in umbilical cord blood – VM.

Such transformations are a natural part of intrauterine development, however, they can also take place in the adult body. They occur during wound healing, but also in many pathological processes, including fibrosis and the growth of malignant tumors. It is not surprising that these transformations are actively studied by representatives of many biomedical specialties.

One of these experiments was recently conducted at the Institute of Biomedical Research named after Whitehead. His collaborators with colleagues from other scientific centers found that mesenchymal cells of epithelial origin have many properties of stem cells existing in adult organisms. This discovery did not follow from any theoretical models and therefore turned out to be completely unexpected.

Its authors do not exclude that their discovery may lead to the creation of fundamentally new technologies for the artificial production of stem cells of various types. In order for a cell to undergo an epithelial-mesenchymal transition, some of its genes must be silenced, while others, on the contrary, begin to work in an enhanced mode. Scientists have a number of methods that allow you to change the activity of genes in cell cultures. This opens up the possibility of purposeful transformation of epithelial cells into mesenchymal cells.

Portal "Eternal youth" www.vechnayamolodost.ru02.07.2008

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