Combining stem cells and silicon nanowires in lab-grown tissue has shown promise as a step toward a new treatment for heart disease, the leading cause of death worldwide, according to a multi-institutional research team. The U.S. National Institutes of Health's National Heart, Lung, and Blood Institute recently awarded the team a five-year, $2.6 million grant to move the work forward.
Researchers from Penn State, Clemson University and the Medical University of South Carolina will work together to combine genetically modified human stem cells - procured from commercially available cell lines - with tiny, conductive wires made from silicon to grow cardiac organoids in the lab. The researchers said they hope to develop the organoids, which are tissues made up of multiple cell types found in the human heart, into a readily available, "off-the-shelf" treatment for heart failure and other cardiovascular diseases. The idea is that the organoids could be transplanted into a heart to repair damage resulting from a heart attack.
Stem cells can be pluripotent, meaning they have the capacity to develop into any cell type in the body, including heart muscle cells, or myocytes. That ability makes human pluripotent stem cells an attractive option for replacing damaged and dead heart muscle, the researchers said. However, when stem cell-derived myocytes are transplanted, the recipient's immune system may not recognize them and trigger an immune response. To minimize the risk of rejection, the team aims to create universal donor stem cells.
"My lab will work on generating the universal donor stem cells through genome editing of pluripotent stem cells," said Xiaojun "Lance" Lian, associate professor of biomedical engineering and of biology at Penn State. "Through genome editing, these cells will become cells that can be transplanted into patients without immune rejection."
The researchers will test whether the genetic modifications affect the functioning of the myocytes derived from stem cells. They also will investigate if the genetic modifications impact the silicon nanowires, which Clemson bioengineering researchers previously found could improve the electrical connectivity and overall function of lab-grown tissue. If the researchers successfully develop universal donor stem cells that can differentiate into myocytes without negatively impacting their function or that of the silicon nanowires, Lian said the resulting cardiac organoids could potentially help treat heart failure and other cardiovascular diseases.
Lian said that the proposed universal donor stem cells could also potentially make other types of therapeutic cells, such as beta cells to treat diabetes.
