In the early 1900s, Henry Ford was lauded for his use of the assembly line, which allowed the rapid, reliable and uniform production of over 15 million Model T automobiles. By codifying each step of production and using identical, interchangeable parts, he brought car ownership within reach of the average American and changed the face of our country.
Now Stanford cardiologist Joseph Wu, MD, PhD, and instructor Paul Burridge, PhD, have done something similar with stem cells. They’ve devised a way to create large numbers of heart muscle cells called cardiomyocytes from stem cells without using human or animal-derived products, which can vary in composition and concentration among batches. Their technique was published Sunday in Nature Methods. Wu, who is the director of the Stanford Cardiovascular Institute explained to me in an e-mail:
This technique solves an important hurdle for the use of iPS-derived heart cells. In order to fully realize the potential of these cells in drug screening and cell therapy, it’s necessary to be able to reliably generate large numbers at low cost. Due to their chemically defined nature, this system is highly reproducible, massively scalable and substantially reduces costs to allow the production of billions of cardiomyocytes matching a specific patient’s heart phenotype.
Chemically defined cell culture means that scientists know exactly what (and how much) is in the liquid in which the cells are grown. In contrast, many common cell culture methods involve the use of nutrient-rich broth derived from animal or human sources. These liquids are teaming with proteins, some known and some unknown, that can promote stem cell growth. They get the job done, but their components can vary among batches and the outcome isn’t always reproducible.
In the new method, Wu and his colleagues collected cells from the skin or blood of an individual. They used a virus called the Sendai virus encoding four reprogramming genes to create induced pluripotent stem cells. These cells were then grown in a liquid in which everything needed for growth was precisely defined. As Wu explained, “This approach gives us an opportunity to fully understand the molecular and macromolecular requirements for cardiac differentiation and eliminates any animal-derived components that were previously used.”
The researchers found they were able to produce about 100 cardiomyocytes for every one stem cell by following a systematic series of steps and using a growing medium that contained just three well-defined components. They showed the technique worked on 11 different batches of induced pluripotent stem cells. The cardiomyocytes were more than 95 percent pure, making it easier to get large numbers of cells to study disease processes or to test the effects of compounds during drug development. According to Wu:
We can use this approach to assess the effect of a particular medication on a specific patient’s heart cells, to discover new drugs, to better understand the process of heart development and to generate cardiomyocytes for use in regenerative medicine approaches, such as for injection into the heart to aid recovery after a heart attack. The system also serves as a platform to study cardiomyocyte subtype specification and maturation.
Of course, stem cells are nothing like automobiles, and regular people aren’t lining up clamoring for a fresh vial of heart muscle cells. But it’s possible that the ability to reliably generate large numbers of cardiomyocytes for study and therapy could be as transformative to cardiac medicine as the Model T was to our grandparents and great grandparents.
Previously: Oh grow up! “Specialized” stem cells tolerated by the immune system, say Stanford researchers, Stem cell medicine for hearts? Yes, please, says one amazing family and “Clinical trial in a dish” may make common medicines safer, say Stanford scientists
Photo by Kyle Harris