By Kaitlyn Gerber, Carleton College
Approximately every 25 seconds, an American will have a “coronary event,” more commonly known as a heart attack. Heart disease is the leading killer of both adult men and women in the United States, as well as the leading cause of other debilitating health problems. As a result, the majority of Americans either know someone who has been affected by heart disease, or suffer from it themselves.
Even when heart attacks are not fatal, they can leave the affected individual with debilitating tissue damage in their hearts. Now, however, after over a decade of research, a team of scientists at the Perelman School of Medicine at the University of Pennsylvania have managed to “reprogram” other types of cells into heart cells, so that they may be used to repair damaged coronary tissues. This breakthrough, published in the July 8 issue of Proceedings of the National Academy of Sciences, is an extremely significant step for the treatment of heart attacks and coronary disease, and may eventually help save lives.
The team* of investigators from the University of Pennsylvania's Perelman School of Medicine was led by Dr. James Eberwine, Elmer Holmes Bobst Professor of Pharmacology, and Dr. Tae Kyung Kim, post-doctoral fellow. By experimenting with different methods of RNA transfer between cells, the research team managed to transform one type of cell directly into another. The key lies directly in natural cellular processes. A particular individual's cells all contain the same set of genes encoded in DNA; however, within each cell, different genes are "expressed," resulting in many cells with different appearances and functions. All human cells also contain molecules called messenger RNA (mRNA), which act as chemical blueprints for making proteins in a process called translation. RNA translation produces proteins depending on which genes are to be expressed in the cell. Thus, the genes determine the properties of the mRNA, and the mRNA, in turn, determines the appearance and behavior of the cell.
To make this particular transformation, the team of researchers extracted large amounts of mRNA from heart cells, and then injected it into two different kinds of “host cells:” astrocytes (star-shaped brain cells) and fibroblasts (skin cells). This change was done through a process called lipid-mediated transfection, which involves creating pores in the cell membrane, so that new material can be brought into the cell. Because each new host cell in this study contained an overabundance of heart cell mRNA, the cells began translating the heart cell mRNA, rather than their own original mRNA. As a result, heart cell proteins were produced, and eventually, the entire cell was transformed from a skin or brain cell into a functioning heart cell.
The research team called this process Transcriptome-Induced Phenotype Remodeling (TIPeR). Previous research in the field had focused on another process, the Induced Pluripotent Stem Cell Procedure, in which cells are transformed back into their original embryonic form, and "reprogrammed" to develop as a new type of cell. TIPer, however, is a new procedure that skips this middle step, changing the cell directly from one form to the next without returning to its developmental state. TIPeR is therefore an important breakthrough in stem cell research, because it makes the process of transforming one cell into another much more efficient and quick.
The process is still too time-consuming to be an instant "miracle cure," but it is an important step in the treatment of heart disease. In addition, creating new heart cells from individual patients could allow for personal screenings for the efficiency of specific treatments. Hopefully, treatments such as this one will soon be important additions to medical treatments for America’s leading killer.
*For a full list of names of research investigators, please scroll down to the bottom of this article.
Kaitlyn Gerber is an incoming sophomore at Carleton College, where she plans to major in biology. Originally from Ridgefield, CT, she likes soccer, reading, and science, especially ecology and astronomy.