Stem cells have long been heralded for their regenerative potential and implications in studying development and disease – they’ve already had some success treating spinal cord injuries and diabetes. And now, in a new study at the University of Virginia (UVA) School of Medicine, mouse embryonic stem cells have been used to make the most sophisticated in vitro (in a dish) model of a mammal ever created in such a way. The mouse embryoid features a beating heart and is in the process of developing its muscles, blood vessels, gut, and nervous system – all in a petri dish.
Stem cells are a type of cell whose fate is not predetermined. They have the ability to develop into many – in some cases any – of the more than 200 cell types in our bodies. This gives them massive potential in the treatment of disease and growth and repair of tissues. Harnessing their ability to differentiate into a single cell type is challenging enough, but using them to build complex models with multiple cell types is a different ball game – the team at UVA really had their work cut out.
The research, published in Nature Communications, builds on previous work by the same authors – in their 2014 study, they identified the conditions necessary to artificially develop a zebrafish embryo from scratch. This knowledge was to become crucial in overcoming the multitude of challenges faced in stem cell modeling. Namely, failure to develop properly or organize correctly, as happened in previous models. The current study, however, generated a well-developed mouse embryo with correctly organized cells and tissues: notochord (which will go on to become the backbone), digestive tract, beating heart, and neural tube (which will later become the brain and spinal cord). The latter is a precursor to the central nervous system and represents the first time this has been successfully developed in vitro.
"What is amazing is that we can get the variety of tissues that are present in an authentic mouse embryo," study author Christine Thisse, PhD, said in a statement.
The artificial tissues are not only present, but they are also functional: "Human organs are made of multiple cell types that originate from different parts of the growing embryo," Bernard Thisse, PhD, also an author on the paper, explained. "The only way to have all the variety of cells necessary to the formation of functional organs is to develop systems in which all precursor cells are present. The embryo-like entities we have engineered using stem cells are providing just this."
While this is undoubtedly a huge step towards scientists using stem cells to successfully mimic mammalian development, it is by no means the end of the road. "The embryoids we are currently producing lack the anterior brain domains," Bernard Thisse said. Because of this, their development stops in the middle of gestation. So we might not yet be at the point where we can grow a tiny baby mouse in a dish using just a handful of cells, but the great strides made by the study will advance the field of stem cell research significantly. The authors remain optimistic that the techniques they’ve developed will allow them, in future, to generate embryoids that contain all tissues and organs, including the anterior brain.
For now, this remarkable model will shed light on mammalian development and be a powerful tool in other in vitro studies, as well as in disease modeling. It could, potentially, aid in the creation of new drugs, and be used to grow tissues and organs for transplant patients.