Published on: January 11, 2017
Article Source: Penn State
Abstract: Human stem cells can be utilized to generate the cells that cover the external surface of a human heart — epicardium cells — according to a multidisciplinary team of researchers
A multidisciplinary team of researchers from Penn State has uncovered a new process by which human stem cells can be made to generate the cells that cover the external surface of a human heart, i.e. epicardium cells.
“In 2012, we discovered that if we treated human stem cells with chemicals that sequentially activate and inhibit Wnt signaling pathway, they become myocardium muscle cells,” said Xiaojun Lance Lian, assistant professor of biomedical engineering and biology, who is leading the study at Penn State. Myocardium, the middle of the heart’s three layers, is the thick, muscular part that contracts to drive blood through the body.
The Wnt signaling pathway is a group of signal transduction pathways made of proteins that pass signals into a cell using cell-surface receptors.
“We needed to provide the cardiac progenitor cells with additional information in order for them to generate into epicardium cells, but prior to this study, we didn’t know what that information was,” said Lian. “Now, we know that if we activate the cells’ Wnt signaling pathway again, we can re-drive these cardiac progenitor cells to become epicardium cells, instead of myocardium cells.”
The results of this study has been published in Nature Biomedical Engineeringand has brought the researchers a step ahead in regenerating the complete heart wall. The researchers made use of morphological assessment and functional assay, through which they found that the generated epicardium cells were similar to epicardium cells in living humans and those grown in the laboratory.
“The last piece is turning cardiac progenitor cells to endocardium cells (the heart’s inner layer), and we are making progress on that,” added Lian, who led this study.
The current research of generating epicardium cells could prove to be useful in clinical applications especially for patients who suffer a heart attack. According to the Centers for Disease Control and Prevention, every 43 seconds, someone in the United States has a heart attack
“Heart attacks occur due to blockage of blood vessels,”Lian says. “This blockage stops nutrients and oxygen from reaching the heart muscle, and muscle cells die. These muscle cells cannot regenerate themselves, so there is permanent damage, which can cause additional problems. These epicardium cells could be transplanted to the patient and potentially repair the damaged region,” added Lian.
The study involved engineering the human stem cells to become reporter cells which means that cells expressed a fluorescent protein only when they became epicardium cells.”We treated the cells with different cell signaling molecules, and we found that when we treated them with Wnt signaling activators, they became fluorescent,” said Lian.
“In addition to generating the epicardium cells, the researchers also can keep them proliferating in the lab after treating these cells with a cell-signaling pathway Transforming Growth Factor Beta (TGF) inhibitor,” said Lian based on another finding.
Lian said, “even after 50 days, our cells did not show any signs of decreased proliferation. However, the proliferation of the control cells without the TGF Beta inhibitor started to plateau after the tenth day.”
The group will continue working together to move ahead in their research on regenerating endocardium cells.
“We are making progress on that inner layer, which will allow us to regenerate an entire heart wall that can be used in tissue engineering for cardiac therapy,” said Lian.
Xiaoping Bao, XiaojunLian, Timothy A. Hacker, Eric G. Schmuck, Tongcheng Qian, Vijesh J. Bhute, Tianxiao Han, Mengxuan Shi, Lauren Drowley, Alleyn T. Plowright, Qing-Dong Wang, Marie-Jose Goumans, Sean P. Palecek. Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions. Nature Biomedical Engineering, 2016; 1 (1): 0003 DOI: 10.1038/s41551-016-0003.