Hopes dashed?
The effect of stem cells on heart regeneration in the clinic has not yet been confirmed
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Scientists of the Tomsk Research Institute of Cardiology have completed clinical studies to assess the effect of bone marrow stem cells, serum levels of cytokines and growth factors on human heart regeneration. The results of many years of research have been published in the highly rated journal PLOS One.
Experiments conducted in the early noughties showed that transplantation of bone marrow stem cells to animals with simulated myocardial infarction leads to regeneration of heart tissue. Attempts were immediately made to quickly transmit this data to the clinic – the Tomsk Research Institute of Cardiology project received several grants from the Russian Foundation for Basic Research and was carried out in cooperation with Moscow State University and the Almazov Center in St. Petersburg.
In exploratory limited clinical trials, researchers isolated autologous mononuclear stem cells from bone marrow and injected them into the coronary artery or injected them into the myocardium during open-heart surgery.
Clinical studies have resulted in several methods of isolation, selection, visualization and transplantation of cells, which have shown short-term effectiveness. However, after a few years, when quantitative data reflecting short-term and long-term effects accumulated, it became clear that the expectations from the use of the method were not met. The effect revealed in the initial experiments could not be reproduced in the clinic.
"It didn't work out not only for us. The ten–year boom in stem cell research has led to a very modest result that is not capable of changing the clinical situation," says the director of the Cardiology Research Institute, project manager Vyacheslav Ryabov. – Of course, we started looking for problems and barriers that did not allow us to reproduce the results of animal experiments. In particular, one of the areas of our work was to determine the effect of serum levels of cytokines and growth factors on the effectiveness of autologous bone marrow cell transplantation."
The researchers found that immediately after transplantation, stem cells reduced the inflammatory activity of the immune system, but this had little effect on the clinical result. In addition, the initial, before the intervention, serum levels of some cytokines and growth factors significantly differed in different patients, which is probably due not only to the reaction to the disease, but also to genetic characteristics.
"This baseline level is directly related to the long–term prognosis - in other words, what the patient will come to five to seven years after a myocardial infarction. At the same time, the investigated method of cell therapy did not allow to influence these indicators. She can help someone, but not in general," explains Vyacheslav Ryabov.
Also, different methods of introducing stem cells into the heart did not justify themselves. Using radionuclide tags, scientists have tracked that they remain in the myocardium in very small quantities. This is another reason for the low effectiveness of the new treatment method. In addition, there is a hypothesis that stem cell transplantation is a dead end. Fundamental research on modern high-resolution equipment will allow us to overcome some of the already known barriers, discover new patterns and gain new knowledge about heart regeneration.
"Apparently, we lack fundamental knowledge about the regeneration of the heart. We need new data on tissue engineering, new molecules and biological targets, new mechanisms. This knowledge could allow us to intervene in the regeneration of the myocardium and, perhaps, even control the process, without counting on the simple transfer of stem cells to the damaged heart," he believes Vyacheslav Ryabov.
Before finally putting an end to the cell therapy of infarction, we will wait for the results of a 2–order of magnitude larger clinical study of the same technique described by Tomsk scientists - VM.
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