Amazing stuff! When will we have a brain on a chip?
"...morphogens, molecules that are manufactured at specific times and places within the embryo and dispersed to dictate the location and shape of our organs. The varying concentrations of morphogens serve as a map that guides the stem cells to their destination and destiny.
Morphogen concentration maps are key to all technologies aimed at making organoids, the laboratory-manufactured miniature versions of living organs that in the past decade have taken over the world of developmental biology. But until now, most researchers have been producing organoids using uniform concentrations of morphogens in petri dishes, which limited them to growing small sections of an organ in each dish, rather than generating a single, miniature version of the complete organ. Now, however, researchers ... have created a miniature version of the entire embryonic central nervous system, from the brain to the bottom of the spinal cord, using a microfluidic chip that mimics the dispersal of the morphogens during embryonic development. ...
The researchers note that their chip does not emulate the earliest stages of the central nervous system’s development. ..."
From the abstract:
"The human nervous system is a highly complex but organized organ. The foundation of its complexity and organization is laid down during regional patterning of the neural tube, the embryonic precursor to the human nervous system. Historically, studies of neural tube patterning have relied on animal models to uncover underlying principles. Recently, models of neurodevelopment based on human pluripotent stem cells, including neural organoids and bioengineered neural tube development models have emerged. However, such models fail to recapitulate neural patterning along both rostral–caudal and dorsal–ventral axes in a three-dimensional tubular geometry, a hallmark of neural tube development. Here we report a human pluripotent stem cell-based, microfluidic neural tube-like structure, the development of which recapitulates several crucial aspects of neural patterning in brain and spinal cord regions and along rostral–caudal and dorsal–ventral axes. This structure was utilized for studying neuronal lineage development, which revealed pre-patterning of axial identities of neural crest progenitors and functional roles of neuromesodermal progenitors and the caudal gene CDX2 in spinal cord and trunk neural crest development. We further developed dorsal–ventral patterned microfluidic forebrain-like structures with spatially segregated dorsal and ventral regions and layered apicobasal cellular organizations that mimic development of the human forebrain pallium and subpallium, respectively. Together, these microfluidics-based neurodevelopment models provide three-dimensional lumenal tissue architectures with in vivo-like spatiotemporal cell differentiation and organization, which will facilitate the study of human neurodevelopment and disease."
A patterned human neural tube model using microfluidic gradients (no public access)
Researchers used color-coded proteins to reveal the identity of the cells in the organoids they produced. In four organoids that simulate the embryo’s central nervous system, the magenta marks proteins associated with the development of the forebrain and the midbrain, the green, the hindbrain and the red, the center of the spinal cord
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