Canadian scientists have managed to overcome a key research obstacle to developing regenerative treatments for diabetes and liver disease. This breakthrough utilizes a technique to produce medically useful amounts of endodermal cells from human pluripotent stem cells. This research, which was published in Biotechnology and Bioengineering, is transferable to other areas of stem cell research, and might help scientists find a way to move stem cell treatments from the bench to the clinic.
Dr Mark Ungrin from the University of Toronto said: “One million people suffer from type 1 diabetes in the United States, while liver disease accounts for 45,000 deaths a year. This makes stem cells, and the potential for regenerative treatments, hugely interesting to scientists. Laboratory techniques can produce thousands, or even millions, of these cells, but generating them in the numbers and quality needed for medicine has long been a challenge.”
This work examined using pluripotent stem cells (PSC) to generate endoderm cells. During early embryonic development, the embryo undergoes a remarkable rearrangement process called “gastrulation. Prior to gastrulation, the embryo is one cell layer thick. After gastrulation, the embryo is three cell layers thick. The outer cell layer is called “ectoderm,” and it forms the skin, and the nervous system. The cell layer underneath the ectoderm is the mesoderm, which forms most of the internal organs like bones, muscles, glands, kidneys, reproductive organs, and connective tissue. The lowest layer of cells is the endoderm, which forms the gastrointestinal tract and its associated organs, and the lungs. These three cell layers – ectoderm, mesoderm, and endoderm – are called the “three primary germ layers,” and they form all the internal organs of the body. The ability to differentiate, or transform, PSCs into endoderm cells is a vital step to developing regenerative treatments for these organs.
Ungrin noted: “In order to produce the amount of endoderm cells needed for treatments it is important to understand how cells behave in larger numbers, for example how many are lost during the differentiation process and if all the cells will differentiate into the desired types.”
The technique used by this research team stained cells with vital dyes that allowed them to determine the efficiency of endodermal differentiation. This technique allowed the team to detect cell inefficiencies and develop a new understanding of the underlying cell biology during the differentiation of PSCs into endodermal precursors. This allowed the team to increase effective cell production 35-fold. These results showed significant increases in the quantity of endodermal cells. It also allows workers to scale up the production of useful cells, and ensures PSC survival and effective differentiation. Since creating sufficient quantities of endodermal precursors is one of the bottlenecks of this research, overcoming this bottleneck can potentially help future stem cell researchers navigate the often long and challenging route from laboratory testing to clinical use. It could also accelerate the time from biomedical advance to beneficial therapy, often referred to as the bench-to-bedside process.
Ungrin opined: “Most research in this field focuses on the purity of generated cell populations; the efficiency of differentiation goes unreported. However our research provides an important template for future studies of pluripotent stem cells, particularly where cells will need to be produced in quantity for medical or industrial uses.”