Scalable Manufacture of Biomimetic 3D Neural Organoids
While hPSC-derived cell therapies are now reaching clinical trials, hPSCs greatest impact continues to be providing novel, biomimetic experimental platforms for investigating human development, biology, physiology, and disease. Human PSC-derived models can be personalized to patients via use of induced pluripotent stem cells (iPSCs), and they avoid confounding differences that exist between rodents and humans. Recently, 3-D aggregates of neurally differentiating hPSCs were observed to spontaneously morph in vitro into organotypic masses, a.k.a. cerebral organoids, containing diverse brain tissues. Discovery of this innate emergent behavior raises the possibility that human CNS morphogenesis can be engineered ex vivo to generate diverse brain and spinal cord tissues with biomimetic structure, cellular composition, cytoarchitecture— micro-to-millimeter scale spatial organization of cell phenotypes—, and even function via biomimetic neuronal circuits. However, to realize this possibility, the currently spontaneous and random organoid morphogenesis process must become instructed and standardized, a prerequisite for translation of human neural organoids as clinically predictive models and transplants. In pursuit of this goal, we meld neurodevelopmental and hPSC biology with engineered biomaterial platforms to create novel methodologies for instructing ex vivo, 3D morphogenesis of human neural tissues.
Contacts: Carlos Marti-Figueroa