There are many factors in a progenitor cell’s environment that contribute to the path a stem cell will take, whether it be differentiation, senescence, or apoptosis. These stimuli include chemical, mechanical, and electrical signaling. Over the last decade, a lot of progress has been made toward the discovery of these signals, especially in heart tissue engineering applications.
Heart disease has, unfortunately, been the leading cause of death worldwide for almost a century. The ratio of the already-scarce reservoir of viable donor hearts to patients who need heart transplants decreases with each passing year. Furthermore, while new drugs were being synthesized to treat heart symptoms, they could not fix the problem. Thus, it was necessary to come up with a new solution, and scientists turned to tissue engineering.
The first few trials of heart tissue engineering sought to inject stem cells into the site of cardiac infarctions, or where the heart tissue had died. Stem cells had been discovered to mimic the features of cells in their environment, preferentially differentiating into those cells due to signaling molecules that mature cells released. However, this was precisely the problem: the stem cells injected onto the site of the infarction began taking on characteristics of the cells around it—the dead cells. What was originally thought to improve patients’ lives caused more damage than improvement.
Researchers then began to look at the extracellular matrix (ECM), a protein structure that acts as a support and signaling structure for tissues. The mechanotransduction aspects of the ECM were extensively studied to see how cells sense the mechanical environment provided by the ECM as well as how signals are transduced to trigger pathways. They discovered that by protein combinations in the ECM differ depending on age of the patient and the type of tissue that the matrix surrounds, and by changing the composition of the matrix, stem cells could be made to differentiate into a different type of tissue altogether. In addition to the chemical environment of the matrix, it was discovered that the mechanical stimulus caused by the matrix also had an effect on stem cell differentiation. Mechanical strain, compression, and shear forces contribute to signals that reach all the way down into the nucleus. These small physical signals can cause a complete change in gene expression.
Professor Lauren Black in the Tufts Biomedical Engineering Department, a leading expert in cardiovascular tissue engineering, has been working to create new methods to study the biophysical stimulation of the extracellular environment and how it can lead to cardiac repair. His group built a bioreactor to mimic how heart cells contract, creating an environment that imitates the electrical signals sent to heart cells. His goal was to combine the mechanical stretching and the electrical signaling and determine the relation of the two stimuli with one another, exploring how timing affects cell growth. Data from his research suggests that applying electrical stimulation a delayed time period after mechanical stimulation to the cells contributed to maximizing cell differentiation into the desired tissue. This emphasizes the vitality of signaling in our body’s tissue growth, and with these findings, researchers like Black can better engineer better functioning cardiac tissue.
Morgan, Kathy, and Lauren Black, III. “Mimicking Isovolumic Contraction with Combined Electromechanical Stimulation Improves the Development of Engineered Cardiac Constructs.” Tissue Engineering Part A (2014): ahead of print. Web.