Summary:
A new technique, which allows scientists to generate both embryonic and non-embryonic tissues from cultured stem cells, is a step toward growing donor organs and replacement tissues to combat aging and diseases.
Stem cells can be totipotent or pluripotent meaning that these cells like embryo can develop into any type of tissue in the body. Totipotent stem cells can develop into tissues that support the embryo like placenta. These are called as extra embryonic tissues and are vital in development and healthy growth.
Now, scientists at the Salk Institute, in collaboration with researchers from Peking University, in China, are reporting their discovery of a chemical cocktail that enables cultured mouse and human stem cells to do just that: generate both embryonic and extra-embryonic tissues. This yields new insights into mammalian development that lead to better disease modelling, drug discovery and even tissue regeneration. This could help in treating diseases affecting embryo implantation, placental function, possibly leading to improved in vitro fertilization techniques.
“During embryonic development, both the fertilized egg and its initial cells are considered totipotent, as they can give rise to all embryonic and extra-embryonic lineages. However, the capture of stem cells with such developmental potential in vitro has been a major challenge in stem cell biology,” says Salk Professor Juan Carlos Izpisua Bemonte, co-senior author of the paper and holder of Salk’s Roger Guillemin Chair. “This is the first study reporting the derivation of a stable stem cell type that shows totipotent-like bi-developmental potential towards both embryonic and extra-embryonic lineages.”
Embryonic development:
Once a mammalian egg is fertilized and begins dividing, the new cells segregate into 2 groups: 1. Cells that develop into embryo. 2. Cells that develop into supportive tissues like placenta and amniotic sac.
Because this division of labor happens relatively early, researchers often can’t maintain cultured cell lines stably until cells have already passed the point where they could still become either type. The newly discovered cocktail gives stem cells the ability to stably become either type, leading the Salk team to dub them extended pluripotent stem (EPS) cells.
“The discovery of EPS cells provides a potential opportunity for developing a universal method to establish stem cells that have extended developmental potency in mammals,” says Jun Wu, a senior scientist at Salk and one of the paper’s first authors. “Importantly, the superior interspecies chimeric competency of EPS cells makes them especially valuable for studying development, evolution and human organ generation using a host animal species.”
Pluripotent cells:
To develop their cocktail, the Salk team, together with the team from Peking University, first screened for chemical compounds that support pluripotency. They discovered that a combination of 4 chemicals and a growth factor could stabilize the human pluripotent stem cells at a developmentally less mature state, thereby allowing them to more efficiently contribute to chimera (a mix of cells from two different species) formation in a developing mouse embryo. These findings when applied to mouse stem cell culture, results were surprising giving rise to not only embryonic tissue types but also non-embryonic tissues.
Moreover, the team found that the new mouse stem cells have a superior ability to form chimeras and a single cell could give rise to an entire adult mouse, which is unprecedented in the field, according to the team.
Practical implications:
“The superior chimeric competency of both human and mouse EPS cells is advantageous in applications such as the generation of transgenic animal models and the production of replacement organs,” adds Wu. “We are now testing to see whether human EPS cells are more efficient in chimeric contribution to pigs, whose organ size and physiology are closer to humans.” Human EPS cells, combined with the interspecies blastocyst complementation platform as reported by the same Salk team in Cell in January 2017, hold great potential for the generation of human organs in pigs to meet the rising demand for donor organs.
“We believe that the derivation of a stable stem cell line with totipotent-like features will have a broad and resounding impact on the stem cell field,” says Izpisua Belmonte.