Laboratory-grown human heart cells provide a powerful tool for understanding and potentially treating heart disease. However, methods for producing human heart cells from pluripotent stem cells are not optimal. Fortunately, a new study from the University of Wisconsin-Madison Stem Cell & Regenerative Medicine Center offers a key insight that will help researchers grow heart cells from stem cells.
The research, recently published in eLife, investigates the role of extracellular matrix proteins (ECMs) in the generation of cardiac cells derived from human pluripotent stem cells (hPSCs). ECM fills the space between cells, providing structural support and regulating the formation of tissues and organs. With a better understanding of ECM and its impact on heart development, researchers will be able to more effectively develop heart muscle cells, called cardiomyocytes, that could be useful for heart repair, regeneration and cell therapy.
“It has been overlooked how ECM affects the generation of hPSC cardiomyocytes,” says Jianhua Zhang, a senior scientist at the Center for Stem Cell and Regenerative Medicine. “The better we understand how soluble factors and ECM proteins work in cell culture and differentiation, the closer we get to our goals.”
Researchers like Zhang have been looking to improve the differentiation of hPSCs into cardiomyocytes, or the ability to take hPSCs, which can be renewed indefinitely in culture while maintaining the ability to become almost any cell type in the human body and convert -those in heart muscle. cells. To investigate the role of ECM in promoting this cardiac differentiation of hPSCs, Zhang tested a variety of proteins to see how they affected stem cell growth and differentiation, specifically, ECM proteins included. laminin-111, laminin-521, fibronectin, and collagen.
“Our study showed that ECM proteins play an important role in the adhesion, growth and cardiac differentiation of hPSC. And fibronectin plays an essential role and is indispensable in the cardiac differentiation of hPSC,” says Zhang . “By understanding the roles of ECM, this study will help develop more robust methods and protocols for hPSC-CM generation. In addition, this study not only helps in the field of cardiac differentiation, but also in other differentiations. of lineage “.
While the new study provides an important insight into the development of heart cells, it is based on a 2012 study led by Zhang that looked at the most efficient way to develop stem cell differentiation.
“This study is actually a follow-up paper on the Matrix Sandwich Method that we developed for efficient cardiac differentiation of hPSCs,” says Zhang. “In order to grow the stem cells, we had to have an ECM layer on the bottom of the plate. Otherwise, the stem cells would not adhere to the plate. Then we would add another ECM layer on top of growing stem cells and we found that this helped promote more effective differentiation. ”
Although it was clear that this layered method, or sandwich, more efficiently and reproducibly differentiated hPSC cardiomyocytes, the researchers did not fully understand why. The new study explains why ECM layers are crucial and identifies fibronectin as a key ECM protein in the development of hPSC cardiomyocytes.
“The most exciting part of this study is that I now understand why the Matrix Sandwich method worked. We were able to identify fibronectin and its integrin receptors, as well as downstream signaling pathways in this study,” Zhang explains. . “With a better understanding of the roles of ECM in stem cell growth and cardiac differentiation, we now hope to investigate the role of fibronectin and other ECM proteins in promoting hPSC cardiomyocyte transplantation for cell therapy. · Lular “.
The next step could help researchers realize the full potential of using hPSC cardiomyocytes for disease modeling, drug screening, cardiac regeneration, and cell therapy. This is very significant for Zhang, who started working in cardiovascular research more than 16 years ago.
“I became interested in stem and heart cell research when I started working with stem cells and saw them become heart cells beating in a cell culture dish under a microscope.” , says Zhang. “It was amazing. I’ve been increasingly dedicated to this research and I can really see the potential of using stem cell technologies to cure diseases and improve our health.”