Hopes and promises of stem cells
Alexey Levin, Voice of America
Current modelsOne of the most sensational scientific achievements of the outgoing year was the development of methods for genetic reprogramming of bodily (as biologists say, somatic) human cells, converting them into full-fledged analogues of embryonic stem cells.
This was announced in the second half of November by the laboratory staff of Professor James Thomson of the University of Wisconsin and researchers at Kyoto University led by Professor Shinya Yamanaka.
Both Japanese and American scientists have "elevated" somatic cells to stem cells by transplanting four genes into them that trigger such a transformation. Both groups chose human fibroblasts, one of the varieties of skin and connective tissue cells, as the starting material. Two of the four transplanted genes were also identical, and the other two were different.
However, in both laboratories, cells were obtained that, judging by the results of all the tests carried out, have the same universal ability to transform into specialized cells of any tissue as real embryonic stem cells. They are commonly referred to as induced pluripotent stem cells (iPSC) – induced pluripotent stem cells (iPSC).
Now a new success has been achieved on this path. Researchers from Harvard University and associated medical centers, led by George Daley, used a Japanese technique to remake somatic cells of several types at once. They turned lung and skin cells of a human fetus, skin cells of a newborn baby and adult skin cells taken from a voluntary donor using biopsy into IPSC.
Genetic programmingMolecular biologists at the University of California have confirmed the possibility of genetic reprogramming of adult somatic cells into full-fledged analogues of embryonic stem cells.
The staff of the Center for Regenerative Medicine and Stem Cell Research, headed by Catherine Platt and William Lowry, also managed to turn fibroblasts into iPSCs, and for this purpose only four additional genes were enough to be planted again. Thus, the effectiveness of the new technique of genetic reprogramming of human fibroblasts has already received the second independent confirmation.
Insulin from stem cellsCalifornia-based biotech company Novocell has taken the first steps towards using human embryonic stem cells to treat diabetes.
This experiment was performed in two stages. First, the researchers grew cultures of such cells and forced them to give rise to insulin-producing islet beta cells of the pancreas.
At the second stage, the scientists injected the cells obtained "in vitro" to mice whose own beta cells had previously been destroyed. They took root in a new place and synthesized insulin within a few months. The company's employees reported these results at the international stem cell conference, which took place in the French city of Evry.
However, the success of this experience cannot be called one hundred percent. The transplanted cells produced insulin only when the mice were fed food with a large amount of sugar. The experimenters believe that the transplants did not work at full capacity, since the progenitor stem cells still did not develop to fully functional beta cells. According to scientists, this problem will be solved, but not in the near future. In any case, Novocell plans to start clinical trials of its therapy no earlier than 2010.
Muscle protectionThe staff of the University of Texas Medical Center demonstrated the fundamental possibility of using embryonic stem cells to combat muscular dystrophy.
This name unites a whole family of diseases that lead to the weakening and atrophy of certain muscle groups. The affected muscle fibers gradually degenerate and are replaced by connective and adipose tissue. Muscular dystrophy is most often caused by gene mutations and is, as a rule, incurable.
Texas scientists carried out their research on mice. First, they learned how to grow muscle tissue cell cultures from the embryonic stem cells of these animals, which after transplantation did not give rise to cancerous tumors. The solution of this problem turned out to be very difficult and required long experimentation. Then they artificially induced in mice a disease similar to the most common form of muscular dystrophy, Duchenne dystrophy. To do this, a toxin was injected into the hind limbs of the animals, blocking protein synthesis, which is affected by this disease. As a result, they developed progressive muscle weakness of the same type that occurs with Duchenne dystrophy.
At the final stage of the experiment, the animals were injected with muscle cells grown in the laboratory, which not only took root, but also formed healthy and fully functional muscle fibers. Although this procedure did not lead to a complete cure of the four-legged patients, their condition improved markedly. The head of the research group, Rita Perlingeiro, believes that the results obtained are very encouraging.
IPSK vs SKAAmerican scientists with the help of IPSC – induced pluripotent stem cells – helped mice with sickle cell anemia.
This hereditary disease affects red blood cells, red blood cells. It is caused by a local mutation of a gene that encodes the structure of hemoglobin, a complex protein with which red blood cells transport oxygen. Hemoglobin molecules attach this gas during blood circulation through the lungs and then transfer it to various tissues.
Normal hemoglobin captures and gives away oxygen atoms without changing its properties. Hemoglobin molecules with a structural defect, after the release of oxygen, stick together and cause deformation of red blood cells, which lose their discoid shape, lengthen and sharpen. Abnormal sickle-shaped red blood cells not only carry oxygen worse, but also clog small blood vessels, causing inflammatory processes in the surrounding tissues.
Sickle cell anemia is not treated with medications, but in principle it can be combated through gene therapy. Six years ago, the first successes were achieved on this path. Researchers from the USA and Canada have integrated corrective genes into the hereditary apparatus of the modified immunodeficiency virus and injected it directly into the bone marrow of sick mice. This procedure led to partial or complete recovery of the experimental animals. However, this technique has not yet been tested in humans.
And now American scientists have achieved a new success – so far again only on animal models. Researchers from the Whitehead Institute of Biomedical Research, the Massachusetts Institute of Technology and the University of Alabama reported in the online version of the journal Science that they were able to significantly reduce the symptoms of sickle cell anemia in mice using IPSC.
Mouse iPSCs have been created since last year. Now such cells have been used for gene therapy of sickle cell anemia. Tim Townes, a professor at the University of Alabama, and his colleagues grew a culture of fibroblasts from sick mice and converted them into iPSCs in a standard way. Then they injected a normal hemoglobin gene into them and forced iPSCs with this gene to give rise to specialized hematopoietic stem cells. At the final stage of the experiment, these cells were injected into the same mice that had previously been exposed to penetrating radiation. The radiation destroyed the bone marrow tissues that had previously produced defective red blood cells.
And the transplants did not fail. They took root in the bone marrow, got involved in its work and started the production of red blood cells with unspoiled hemoglobin. Within a few weeks after transplantation, the condition of the animals changed dramatically for the better.
Experimental results of this kind are commonly called proof of principle. Now we can say that nature, apparently, does not prohibit the use of IPSC for the treatment of sickle cell anemia. However, experiments on mice are still very far from clinical experiments. So far, no one can say when they will begin and what they will lead to. But it's easier to hope now.
Getting out of a heart attackScientists from the USA and Germany have successfully tested an experimental method for the treatment of acute cardiac circulatory disorders on mice.
Among the numerous dangers that threaten patients of cardiac clinics, one of the first places is occupied by a pathological increase in contractions of the cardiac ventricles. Doctors call this type of arrhythmia ventricular tachycardia. According to medical statistics, it is the main cause of sudden death of people who have suffered a myocardial infarction.
The staff of three American research centers and the University of Bonn conducted experiments on mice with artificially induced localized heart attack. These animals were implanted with specialized embryonic stem cells programmed to turn into cardiomyocytes, heart muscle cells. The transplanted cells have taken root well and have taken a full part in the transmission of electrical impulses that control heart contractions. As a result, the animals' heart function has normalized.
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13.02.2008