A Robust Human Stem Cell Based System For Anatomically Correct Neural Tube Morphogenesis

Morphogenesis is the biological process that causes a cell, tissue or organism to develop its shape. Understanding the morphogenesis of human embryos is a fundamental question in the physics of life with strong medical implications. 3D human stem cell cultures (organoids) capable of recapitulating selected aspects of human organ formation have greatly advanced our understanding of cell fate during organ formation. However, organoids still yield unreproducible and anatomically incorrect tissue shapes and cell fate patterns. Additional systems are used to apply stem cells into scalable, controlled and functional tissues, but these systems limit their shape and do not allow for self-organization as in embryonic development. Thus, new approaches are required in order to study human organ morphogenesis.

Researchers at the University of California, Santa Barbara have addressed the difficulty of studying human organogenesis by creating a reproducible and scalable approach for studying organogenesis in a dish, which is compatible with live imaging. This is achieved by applying surface micro-patterning to precisely control cell fate in 2D stem cell sheets while allowing for self-organization of tissue shape in 3D. In contrast to animal studies, neural and epidermal human tissues are necessary and sufficient for folding morphogenesis in the absence of mesoderm activity. This technology models neural tube defects by interfering with biological signals that regulate tissue mechanics. The potential applications of this invention reach beyond neural tube defects and can add significant benefits to the study of human organ morphogenesis in health and disease.