Scientists have resorted to stem cell-based treatments to help improve cardiac regeneration following ischemia damage and substitute deceased cardiac material with fresh, functioning material.
Nevertheless, less than 1 percent of cell lines survived transplantation into the cardiac in the majority of instances, owing to the cells’ incapacity to comply with the metabolic requirements of the ischemia microenvironment.
Heart Development Protein Enhances Stem Cell Approach For Heart Regeneration
In a new study, researchers from Temple Lewis Katz School of Medicine reveal that this barrier can be crossed, at minimum in mice, by reintroducing LIN28—a protein typically produced in the embryonic heart into stem cells obtained from mature cardiac muscle. Adolescent heart cells become highly metabolically adaptable as a result of LIN28, considerably increasing overall prospects of surviving.
The heart is the most important organ in the human body. With age, the walls of hearts get damaged, which affects their functions and capabilities. The team of experts has found the protein which affects the capacity of the heart with its functions and rhythms that can affect one’s health.
The capability of the mammalian cardiac to mend itself after damage decreases with aging. Injuries caused by traumas like heart ischemic and cardiac arrest that are linked to low oxygenation concentrations in the circulation could enable the cardiac to perform at a lower capability, rendering it hard for sufferers to go about their daily lives.
“LIN28 is very active in the developing heart, but not in the adult heart,” explained Mohsin Khan, Ph.D., Assistant Professor of Cardiovascular Sciences at the Cardiovascular Research Center at the Lewis Katz School of Medicine and senior investigator on the new study. “We found that when we expressed LIN28 in cardiac stem cells from adult heart tissue, the adult cells were reprogrammed to have metabolic characteristics of young, developing heart cells. The process was essentially like reverse aging.”
The fetal cardiac is designed to survive in low-oxygen environments. Yet, this low-oxygen sensitivity is lost after birth, and by maturity, the cardiac is particularly susceptible to oxygen shortages. Variations in cell respiration are to blame for this transition, and current research suggests that metabolic abnormalities in the cardiac play a role in determining stem cell destiny after transplant.
The researchers first tested the impact of reinstating LIN28 transcription in mature mouse CTSCs in vitro on signaling systems important in cellular metabolism, development, and repair. They discovered that LIN28 transcription triggered a powerful regeneration mechanism in CTSCs, allowing them to proliferate and survive in the face of oxidative damage.
The changes were connected to the Let7/PDK1 signaling system, which is recognized to control aerobic metabolism in cells, according to scientists. Transplanting LIN28-expressing CTSCs into the hearts of mice who had experienced a heart attack improved heart shape and functioning significantly. Such benefits are transmitted through the identical mechanisms that are discovered in the in vitro tests.
Dr. Khan & colleagues wanted to see if metabolic controls that were produced in the growing heart may give heart tissue-derived progenitor cell cells some metabolic flexibility in their latest research (CTSCs).
CTSCs are found in all newborn and adolescent cardiac tissues, but only the growing cardiac expresses LIN28. CTSCs have regeneration ability in adolescent cardiac muscle but are usually inactive.
“LIN28 modified energy production in CTSCs, leading to the secretion of many factors that are beneficial for heart cell survival,” Dr. Khan explained. “Overall, the cells took on a more youthful phenotype.”
Dr. Khan’s next step is to test the research discoveries in a larger animal model and see if LIN28 can reprogram human-derived cardiac stem cells. “These studies could have important implications for how we approach stem cell therapy for heart disease in humans,” he said.
