Myocardium, heal yourself

SLY_G, Geektimes based on ScienceDaily: Stem cell exosomes used to induce damaged mouse hearts to self-repair

The work of biologists led by Dr. Raj Kishore of Biology from Temple University Medical School sheds light on the role of exosomes in the functioning of the body and is potentially able to take a new step in the treatment of a common disease – myocardial infarction.

Exosomes are microscopic extracellular vesicles (vesicles) up to 100 nm in diameter, secreted into the intercellular space by cells of various tissues and organs. They were discovered in the 80s of the last century, and at first they decided that in this way the cells get rid of unnecessary waste products.

But later, when studying the work of cancer cells, biologists discovered that it was not waste at all, but a kind of communication means – like notes in bottles thrown into water. With their help, cancerous tumors communicated with their distant metastases. A little later it became clear that almost all cells in the body use such a mechanism to communicate with each other. In addition, exosomes are involved in many other processes, and their full role has not yet been studied.

How exosomes appear / Wikipedia

Biologists at Temple University have been studying ways to restore the heart after a heart attack. It is known that the heart practically does not know how to heal itself – injuries as a result of a heart attack remain scars on the heart, it has to work in an enhanced mode to ensure blood pumping, heart tissues grow, and the compression force decreases.

It would seem that this disease simply needs to be cured with the help of stem cells – those of them that are pluripotent (can turn into any desired cell). Unfortunately, the simple introduction of stem cells into the heart tissue does nothing – usually most of them just die. And with the surviving cells there is another risk – they can turn into a teratoma, a tumor in which there is porridge from completely different tissues of the body. In some cases, such a tumor appears in the body as a result of the presence of an underdeveloped parasitic Siamese twin.

Biologists led by Kishor have been trying for several years to study the role of exosomes in the body. These bubbles contain DNA, mRNA, microRNA and various proteins. mRNA, also known as informational RNA, is actually the instruction by which new proteins are synthesized. Therefore, the team of biologists wondered if it was possible to use these exosomes as commands for heart cells to repair themselves?

The scientists took two groups of mice. One received exosomes extracted from embryonic stem cells. The other, control, is fibroblast exosomes. The hearts of the mice were affected by a heart attack. And the first group of mice showed undeniably better recovery results after the disease. 

They had more muscle tissue surviving, fewer scars appeared on their hearts, and fewer heart tissue died. In the affected area, much better development of the vascular system was noted, which caused an improvement in blood circulation and oxygen supply to the muscle tissue of the heart. The hearts produced more of their own stem cells, which then turned into muscle tissue cells. The hearts of the mice of the first group beat more actively and did not grow as much as in the other group.

A diagram from the article by Khan et al. Embryonic Stem Cell–Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction, published in the open access journal Circulation Research – VM.

"Our work shows that the best way to restore the heart is to strengthen its self–healing capabilities and increase its ability to be treated," said Dr. Kishore. – Thus, it is possible to avoid the risks associated with the occurrence of teratomas and other complications of stem cell therapy. This is a very exciting development in the theory of heart disease."

In the continuation of the study, the scientists checked whether the MIR–294, the microRNA molecule that regulates genes, which is most often found in exosomes, is responsible for these processes. When this molecule is introduced into the stem cells of the heart, which then turn into muscle tissue cells, several processes similar to those that occurred after the introduction of whole exosomes were observed. But it became clear that not only this molecule is responsible for all their useful work.

Future research will help develop exosomal therapy, and in theory will lead us to its use in the treatment of heart attacks in humans.

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24.06.2015