There is an increasing appreciation of the influence of physical factors on neural stem cell biology. 2D experiments have provided compelling evidence that neural stem cell development is directed in part by mechanobiological influences, which refer to the stimuli a cell experiences as a result of movement, geometry or substrate material. As a result, human cerebral organoids are an exciting model to expand on such mechanobiological studies. Their three-dimensional nature makes them suitable  for exploring the potential impacts of physical conditions such as spatial geometry and mechanical stress, capturing the complex progression of stem and progenitor cells into neurons and more accurately mimicking in vivo conditions. In this study, we leverage these strengths by using human cerebral organoids to explore how physical constraint influences the morphological development of human brain tissue. Cerebral organoid precursors were seeded into geometrically distinct microwells and allowed to develop until they exceeded the size of their wells, after which they were released from the constraints. These samples were then allowed to freely mature for a maximum time of 40 days post-confinement, after which they were stained with fluorescent antibodies to highlight neural progenitor cell presence and organization. We report that organoids derived from precursors, confined in microwells with four convex points, exhibited deterioration of stem cell structures known as ‘neural rosettes’ at a rate faster than those cultured in round microwells. Our findings suggest that microtissue geometry may inhibit neural progenitor proliferation and/or organization, resulting in smaller rosettes and a loss of rosette maintenance, even after organoids are removed from confinement. Further investigation is needed to dissect and decouple the potential effects geometry has on paracrine morphogen release and diffusion, mechanical stress and strain and the time points where these effects have the greatest biological impact.

When it comes to the medical field, 3D modeling has previously been used to render anatomical images in greater detail in order to better understand bodily functions. Lately, however, 3D modeling has made waves in depicting diseases, with a focus on their severity and progression. Unlike a model depicting computer graphics, 3D culture models allow cells to interact in three dimensions and better display cell growth and movement, according to the Food and Drug Administration. Culture models are beneficial in replicating the complexities of disease by promoting interactions between cells and providing insight into potential solutions. In this issue of the Journal of Young Investigators, Priscilla Detwieler and her colleagues demonstrate that atelocollagen incorporated in a 3D model is shown to simulate a potential treatment for inflammation-induced osteoarthritis.  

To combat the harmful effects of stress, neuroscientists are pointing to mindfulness, defined as the practice of being fully present and aware of our external environment and our actions, while not being overly reactive or overwhelmed by external events. To shed light on this, JYI interviewed renowned neuroscientist Dr. Alexandra Fiocco, whose expertise lies at the intersection of mindfulness, stress, and cognitive aging. Dr. Fiocco currently does research at Stress and Healthy Aging Research (StAR) Lab and teaches at Toronto Metropolitan University.