Joined by scientists from VistaGen Therapeutics, a team of Canadian, American and British medical researchers have used embryonic stem (ES) cells differentiation cultures to successfully identify, grow and study the earliest cell destined to form the human heart.
This cardiac stem cell is able to produce all three types of cells important to the cardiovascular system. The research was published in the scientific journal Nature, in a paper entitled, ”Human cardiovascular progenitor cells develop from a KDR embryonic-stem-cell-derived population.”
“The achievement is another step towards generating and validating functional human heart cells at a scale and purity that is necessary for pharmaceutical discovery applications and for predictive toxicity screening of new drug candidates,” said Dr. Ralph Snodgrass, VistaGen’s President and CEO. “Furthermore this is a very good example of the use of key developmental switches and factors, combined with the identification and isolation of tissue committed precursors, to increase the efficiency and yield of mature cells critical to pharmaceutical applications,” he added.
VistaGen, a biotechnology company using ES cell technologies to discover and develop drugs, expects to apply the results of this research to further develop its commercial applications of ES cell-derived cardiomyocytes in drug screening and predictive toxicology assays.
The research team was led by Dr. Gordon Keller, director of Toronto’s McEwen Centre for Regenerative Medicine — the stem cell research arm of the University Health Network (UHN). Other collaborators in the landmark cardiac cell study included scientists from the Mount Sinai School of Medicine, Indiana University School of Medicine, the Weill Medical College of Cornell University, and London’s Kings College Department of Infectious Diseases.
“This development means that we can efficiently and accurately make different types of human heart cells for use in both basic and clinical research," Dr. Keller said. He added, "In the future, these cells may also be very effective in testing how they respond to different drugs and in developing new strategies for repairing damaged hearts, following a heart attack."
The study created the cardiac cells by supplying embryonic stem cell cultures with a “cocktail” of growth factors involved in heart development, and then used surface markers to identify a unique precursor cell that is committed to heart development. By isolating this novel cardiac stem cell and supplying the right growth factors at the right time during development, they encouraged the cells to grow into three different types of cells - cardiomyocytes, endothelial cells and vascular smooth muscle cells - each an important constituent of the cardiovascular system.
The identification of this cardiac stem cell and the production of these three cell types will help researchers understand heart development in more detail, and provide an in vitro cardiac system for discovery and drug screening that is more natural and relevant to in vivo responses. When the team transplanted this cardiac stem cell into mice with simulated heart disease, their heart function was significantly improved, offering hope to those aiming to develop this technique for treating human hearts.
VistaGen has collaborated with Dr. Keller, a leading stem cell scientist, on research projects for more than 10 years. In March, 2008, VistaGen announced an expansive new ES cell research alliance with UHN and the McEwen Centre. The new level of collaboration positions VistaGen to continue to leverage the ES cell biology expertise and leading edge ES cell technologies of Dr. Keller’s group.