Crucial bodily functions like heart rate, blood flow, breathing and digestion are regulated by the neurovascular unit. The neurovascular unit is made up of the blood–brain barrier, blood vessels, microglia and smooth muscles under the control of autonomic neurons. Yet how the nervous and vascular systems come together during development to coordinate these functions is not well understood.
Now, using human embryonic stem cells, researchers at University of California and Sanford-Burnham Medical Research Institute created a model that allows them to track cellular behaviour during the earliest stages of human development in real-time. The model reveals, for the first time, how autonomic neurons and blood vessels come together to form the neurovascular unit. The opensource study is published in the journal Stem Cell Reports.
The team state that the new model allows the medical community to follow the fate of distinct cell types during development, as they work cooperatively, in a way that can’t be done in intact embryos, individual cell lines or mouse models. They go on to add that if researchers are ever going to use stem cells to develop new organ systems, they will need to know how different cell types come together to form complex and functional structures such as the neurovascular unit.
The team explain that capillary endothelial cells, the site of anatomical blood–brain barrier, neurons, and nonneuronal cells such as pericytes, astrocytes, microglia together constitute a functional unit, often referred to as a neurovascular unit. The endothelial cells form the blood vessel (vascular) tube; smooth muscle cells cover the endothelial tube and control vascular tone; and the autonomic neurons influence the smooth muscle’s ability to contract and maintain vascular tone, all the while being regulated and protected by microglia.
The current study revealed that separate signals produced by endothelial cells and smooth muscle cells are required for embryonic cells to differentiate into autonomic neurons. The researchers discovered that endothelial cells secrete nitric oxide, while smooth muscle cells use the protein T-cadherin to interact with the neural crest, specialized embryonic cells that give rise to portions of the nervous system and other organs. The combination of endothelial cell nitric oxide and the T-cadherin interaction is sufficient to coax neural crest cells into becoming autonomic neurons, where they can then co-align with developing blood vessels.
In addition to answering long-standing questions about human development and improving the odds that scientists will one day be able to generate artificial organs from stem cells, the new data findings on the autonomic nervous system also has implications for rare inherited conditions such as neurofibromatosis, tuberous sclerosis and Hirschsprung’s disease.
The team surmise that these observations may help to explain certain human disease syndromes in which abnormalities of the nervous system appear to be associated, for previously unclear reasons, with vascular abnormalities. The researchers conclude that modeling human development and disease in the lab must take into account multiple cell types in order to reflect the actual human condition, rather than examining pure populations of one cell type or another.
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
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Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.