Scientists have developed a beating heart of a mouse from stem cells – a development first of its kind and the most sophisticated till date.
The in vitro (in a dish) model is that of a tiny mouse embryo with a beating heart and its muscles, blood vessels, gut and nervous system beginning to develop. This new model, developed at the University of Virginia School of Medicine by Christine and Bernard Thisse, is a major step forward in scientists’ efforts to mimic the natural development of a mammal by using stem cells. Its existence is a wonder that will help scientists understand mammalian development, battle diseases, create new drugs and, eventually, grow tissues and organs for people in need of transplants.
Stem cells are special cells that can turn into other cell types with specific functions. For example, stem cells turn into our hearts, our brain, our bones, our nerves. So scientists have been eager to harness the potential of stem cells, to put them to work to advance medical research and benefit human patients. But building sophisticated models with multiple cell types has proved incredibly challenging. It is far easier to direct the formation of a single cell type in a dish than to conduct the orchestra needed to have an organism develop as in nature.
The Thisses’ new model is notable for its sophistication. It is the first in vitro model of a mammalian embryo with so many tissues to be built from stem cells, the researchers report. Most importantly, those structures are organized as they should be, around the notochord (the precursor of the vertebral column), a defining trait of vertebrate animals. In the Thisses’ model, different cells types are woven together elegantly and correctly – a huge achievement.
To accomplish this, the Thisses and their collaborators had to overcome some of the greatest challenges in the stem cell field. Prior models failed to develop properly, or weren’t organized correctly, or were plagued by other problems. Using their expertise in developmental biology and building on their previous work using cells from fish embryos (published in the journal Science in 2014), the Thisses solved these problems. The result is the beginnings of a mouse in a dish with properly organized cells and tissues. With the Thisses’ model, the notochord is present and accounted for; the digestive tract starts to develop; the heart beats; and, for the first time in vitro, a nervous system develops with the formation of a neural tube.
The Thisses’ new model isn’t a complete mouse yet and can’t develop into one. Key parts are still missing, such as the anterior part of the brain. For now, the development of the embryoids stops at a time corresponding to middle period of gestation of a mouse embryo. The researchers’ real accomplishment is developing an effective approach to creating sophisticated, embryonic-like structures, mimicking the development of a mouse embryo. This advances their field substantially, and it gives scientists more tailored control over stem cells than they have ever known.
The Thisses and their collaborators have published their findings in the scientific journal Nature Communications. The research team consisted of Peng-Fei Xu, Ricardo Moraes Borges, Jonathan Fillatre, Maraysa de Oliveira-Melo, Tao Cheng, Bernard Thisse and Christine Thisse.
The research was supported by the March of Dimes (grant 1-FY15-298), the Jefferson Trust (FAAJ3199) and the University of Virginia. Maraysa de Oliveira-Melo was supported by CNPq-Brazil (200535/2014-5).