22 June 2017

Stem cell therapy can be harmful

The few chances of improving the condition of patients with end-stage heart failure include only heart transplantation and "life-saving" stem cell therapy. However, researchers at Tel Aviv University, working under the guidance of Professor Jonathan Leor, have found that in reality, therapy with mesenchymal stem cells can not only not help, but also worsen the condition of patients.

As part of the work, the authors isolated mesenchymal stem cells from the cardiac and subcutaneous adipose tissue of mice with simulated left ventricular dysfunction 28 days after myocardial infarction or simulated surgery (control group). An in vitro study of these cells showed that left ventricular dysfunction shifted cardiac mesenchymal stem cells towards a pro–inflammatory phenotype characterized by the secretion of pro-inflammatory cytokines - compounds that contribute to the development of an inflammatory reaction. Mesenchymal stem cells of subcutaneous adipose tissue were less affected by this effect.

After that, the researchers injected mesenchymal stem cells or saline solution into the myocardial infarction zone and assessed the degree of damage recovery and the functioning of the affected tissue 28 days after the infarction. According to their observations, transplantation of mesenchymal stem cells of cardiac and subcutaneous adipose tissue isolated from animals with left ventricular dysfunction and in control group mice did not contribute to the process of remodeling and restoration of the functions of damaged tissue. Moreover, mesenchymal stem cells of the cardiac tissue of mice with left ventricular dysfunction even aggravated the depletion of the anterior wall of the heart.

The authors suggested that the pro-inflammatory polarization of mesenchymal stem cells is due to the activation of toll-like receptor-4 (TLR4) expressed on their surface under inflammatory conditions. To test their hypothesis, they analyzed and compared the response of mesenchymal stem cells of the heart tissue of ordinary mice and animals without TLR4 to inflammatory stimulation in vitro. As expected, TLR4-free cells synthesized fewer pro-inflammatory and more anti-inflammatory cytokines under inflammatory activation conditions compared to cells of ordinary animals.

Further confirmation of the hypothesis was obtained in experiments on ordinary mice with simulated myocardial infarctions, which were injected with cardiac mesenchymal stem cells of ordinary animals and mice without TLR4, or saline solution (control group) into the injury zone. After 7 days, the researchers analyzed the size of the infarction zone, the safety of the transplanted cells, the degree of remodeling and the functionality of the damaged tissue.

Compared with mesenchymal stem cells of ordinary mice, TLR4-free cells retained their viability and ability to stimulate regeneration in the recipient's heart tissue. They contributed to a decrease in the infarction zone and an increase in the thickness of the scar forming and a decrease in the severity of left ventricular dilation.

According to Professor Leor, modern approaches to stem cell therapy can be detrimental to the patient, especially when using their own (autologous) cells. In addition to the lack of a positive effect, they can be influenced by the inflammatory environment and further aggravate the condition of the damaged heart muscle. Based on the data obtained, the authors concluded that in the treatment of heart diseases, only mesenchymal stem cells from healthy donors or genetically modified autologous cells with an inactivated Toll-like receptor-4 gene should be used for transplantation. Currently, they are studying the possibility of using one of the methods of genetic engineering (CRISPER) for this purpose.

Article by Nili Naftali-Shani et al. Left Ventricular Dysfunction Switches Mesenchymal Stromal Cells Towards an Inflammatory Phenotype and Impairs Their Reparative Properties Via Toll-Like Receptor-4 published in the journal Circulation.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Tel Aviv University: Stem cell therapy may harm heart disease patients.


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