Protein Heals Cardiac Muscle and Regenerates Organs
A protein that plays a role in the formation of neurons also plays a role in reprogramming scar tissue cells into heart muscle cells.
The intriguing fields of cellular reprogramming and organ regeneration have been the focus of the intense investigation at the University of North Carolina School of Medicine, where scientists have made significant discoveries. This discovery has the potential to play an important role in the development of future therapeutics for cardiac damage
A recently discovered process by researchers at the University of North Carolina at Chapel Hill and published in the peer-reviewed journal Cell Stem Cell enables cells from scar tissue, which are also referred to as fibroblasts, to be reprogrammed so that they can develop into healthy heart muscle cells. This method is not only more simplified but also more effective (cardiomyocytes). It's possible to produce fibrous and hard tissue after a heart attack or due to heart disease, which may eventually lead to heart failure. These cells, known as fibroblasts, are responsible for producing this tissue. One of the potential future treatment methods that is currently being researched as a potential future approach to treating or possibly eventually curing this widespread and sometimes fatal illness is the transformation of fibroblasts into cardiomyocytes.
The surprising answer to the question of the key to the novel method of producing cardiomyocytes was found to be a protein known as Ascl1, which controls the activity of genes and is an essential protein involved in the transformation of fibroblasts into neurons..
According to the senior author of the study, Li Qian, Ph.D., associate professor in the UNC Department of Pathology and Lab Medicine and associate director of the McAllister Heart Institute at the UNC School of Medicine, "It's an outside-the-box finding, and we expect it to be useful in developing future cardiac therapies and potentially other kinds of therapeutic cellular reprogramming."
Adult cells can be reprogrammed to become stem cells through various methods that researchers have developed over the past 15 years. Those stem cells can then be induced to become adult cells of a different kind of adult cell. This process is known as adult cell differentiation. In more recent years, researchers have developed methods that enable cells to be reprogrammed more directly, allowing cells to transition straight from one mature cell type to another. It is hoped that once these techniques have been perfected in terms of their level of safety, efficacy, and efficiency, medical professionals will be able to convert cells that are harmful to patients into cells that are helpful for patients with the use of a simple injection. This has been a long-held goal.
"Reprogramming fibroblasts has been one of the key goals in the study for a very long time," said Qian. "The research has been going in this direction for a long time." "The over-activity of fibroblasts is the underlying cause of many critical diseases and maladies, including heart failure, chronic obstructive pulmonary disease, liver disease, renal disease, and the scar-like brain damage that may be caused by strokes."
The team led by Qian, which included co-first-authors Haofei Wang, PhD, a postdoctoral researcher, and Benjamin Keepers, an M.D./PhD., was able to reprogramme mouse fibroblasts into cardiomyocytes, liver cells, and neurons in the current study by employing three distinct methods that are already in use. During each of these three distinct reprogrammings, the researchers intended to record and investigate the changes that took place in the gene activity patterns of the cells as well as the factors that influence gene activity. This was done in order to understand better how these changes took place.
Unpredictably, the researchers found that the metamorphosis of fibroblasts into neurons activated a group of genes known to be connected with cardiomyocytes. Soon after, they concluded that one of the master programmer "transcription factor" proteins employed to generate neurons was responsible for this activation. This protein's name was Ascl1.
As a result of the fact that Ascl1 activated the genes present in cardiomyocytes, the researchers decided to include it in the mixture of three transcription factors that they were already using to generate cardiomyocytes and see what would occur. They were shocked to find that it considerably increased the efficacy of reprogramming by more than ten times, where the effectiveness of reprogramming is defined as the proportion of cells that have been successfully reprogrammed. They found out that they could now make do without two of the three factors that had been initially included in their concoction. This meant that they just needed to maintain Ascl1 and another transcription factor known as Mef2c.
The protein known as Ascl1, located in cardiomyocytes, is responsible, along with Mef2c, for activating a varied collection of genes. In subsequent research, the scientists found evidence that whereas Ascl1 on its own activates genes for both neurons and cardiomyocytes, in the presence of Mef2c, it takes on a function that is antagonistic to the development of neurons. This was discovered as a result of the discovery that Ascl1 alone activates genes for both types of cells.
According to Qian, "Ascl1 and Mef2c work together to exert pro-cardiomyocyte effects that neither factor alone exerts, making for a potent reprogramming cocktail." Ascl1 and Mef2c work together to exert pro-cardiomyocyte effects that neither factor alone exerts. When working together, Ascl1 and Mef2c can provide pro-cardiomyocyte effects that neither factor can produce on its own.
The primary transcription factors implemented during direct cellular reprogramming are not necessarily specific to the cell type that is the focus of every one of these procedures.
They provide an additional step toward developing potential future treatments for severe diseases that include reprogramming cells, possibly the essential feature of these results. According to Qian, she and the rest of her team members are working toward developing a two-in-one synthetic protein that would include the helpful components of both Ascl1 and Mef2c and would be able to be injected into failing hearts in order to repair them. This protein would be able to save lives and prevent the need for heart transplants.