RNA interference in infarction will turn scar tissue into myocytes
Fibroblasts of the scar tissue of the heart are reprogrammed into cardiomyocytes using microRNA
LifeSciencesToday based on materials from Duke University Health System:
Duke Team Turns Scar Tissue into Heart Muscle Without Using Stem CellsScientists from Duke University Medical Center (Duke University Medical Center), USA, managed to reprogram scar tissue cells formed in the heart after a myocardial infarction into muscle cells without resorting to stem cell transplantation.
Both in vitro studies and, for the first time, experiments on live mice turned out to be successful.
(Article by Jayawardena et al. microRNA-Mediated In Vitro and In Vivo Direct Reprogramming of Cardiac Fibroblasts to Cardiomyocytes is published in the journal Circulation Research – VM.)
Repopulation of a damaged heart with new functional cardiomyocytes remains a difficult task for regenerative medicine. An ideal therapeutic approach would be the direct transformation of damaged areas into functional tissue in situ.
To directly reprogram scar tissue cells – fibroblasts – into cardiomyocytes, American scientists used microRNA molecules –regulators that control the activity of many genes - demonstrating the potential of a simpler tissue regeneration process.
Using a combinatorial strategy, they found a combination of microRNA molecules (1, 133, 208 and 499) capable of inducing direct reprogramming of fibroblasts into cells with cardiomyocyte characteristics. The reprogramming of cells is confirmed by the expression of markers of mature cardiomyocytes, the organization of sarcomeres and the spontaneous flow of calcium ions.
If the planned additional studies on human cells confirm the possibilities of this approach, the way will open to the development of a new treatment method for many of the 23 million inhabitants of the planet suffering from heart failure – a consequence of the replacement of cardiomyocytes in the area of the dead muscle area with scar tissue after a myocardial infarction. Broad horizons will open up in the treatment of other diseases.
A blood clot formed in the coronary artery blocks blood flow and leads to the death of a section of the heart muscle.
The dead heart muscle is practically not restored and is replaced by scar tissue, reducing the ability of the organ to pump blood.
Repopulation of a damaged heart with new functional cardiomyocytes remains a difficult task for regenerative medicine.
Successful experiments on direct reprogramming of scar tissue fibroblasts into cardiomyocytes using microRNAs directly into the heart of mice may eliminate one of the obstacles to the development of regenerative heart medicine – the need for stem cell transplantation.
"This is an important discovery of great therapeutic significance," says Professor of Medicine Victor J. Victor J. Dzau, MD, one of the senior authors of an article published online in the journal Circulation Research. "If it can be done in the heart, then it can be done in the brain, kidneys and other tissues. This is a completely new way of tissue regeneration."
The use of microRNAs for direct reprogramming of cells for tissue regeneration has a number of advantages over genetic methods of reprogramming and stem cell transplantation, whose behavior in the body is still largely unpredictable. The microRNA-based reprogramming approach eliminates several obstacles to the development of regenerative medicine, for example, the danger of unwanted genetic changes in cells, and also removes many ethical issues that concern society in connection with the use of human embryos.
"This is an interesting stage for the science of reprogramming," says the first author of the study Tilanthi Jayawardena, PhD. "This is a very young field, and we are all just beginning to realize what it means to switch the fate of the cell. We believe we have found a way to do this, and our method has great potential."
"We have proved the validity of our concept," Professor Dzau evaluates the results achieved. "So far we are at the very early stage of the study and have only shown that this is feasible in animal models. Despite the fact that this is a very significant step forward, we are not yet ready for testing on the human body."
In the near future, the new approach will be tested on larger animals. If these experiments and further studies on the human body are successful, a new method of therapy can be developed within the next ten years.
Portal "Eternal youth" http://vechnayamolodost.ru02.05.2012