Three-Dimensional Organoid System Transplantation Technologies in Future Treatment of Central Nervous System Diseases

Abstract

In recent years, scientists have made great achievements in understanding the development of human brain and elucidating critical elements of stepwise spatiotemporal control strategies in neural stem cell specification lineage, which facilitates successful induction of neural organoid in vitro including the cerebral cortex, cerebellar, neural tube, hippocampus cortex, pituitary, and optic cup. Besides, emerging researches on neural organogenesis promote the application of 3D organoid system transplantation in treating central nervous system (CNS) diseases. Present review will categorize current researches on organogenesis into three approaches: (a) stepwise, direct organization of region-specific or population-enriched neural organoid; (b) assemble and direct distinct organ-specific progenitor cells or stem cells to form specific morphogenesis organoid; and (c) assemble embryoid bodies for induction of multilayer organoid. However, the majority of these researches focus on elucidating cellular and molecular mechanisms involving in brain organogenesis or disease development and only a few of them conducted for treating diseases. In this work, we will compare three approaches and also analyze their possible indications for diseases in future treatment on the basis of their distinct characteristics.

Figure 1

Steered with the specific spatiotemporal control strategies, a single embryonic stem cell (ESC) or pluripotent stem cell (PSC) can develop to a three germ layer brain and pure neural type. The outline has been depicted in Tao's paper (Tao et al.). BNP: bone morphogenetic protein; ESC: embryonic stem cell; FGF: fibroblast growth factor; LGE: lateral ganglionic eminence; MGE: medial ganglionic eminence; NSC: neural stem cell; PSC: pluripotent stem cell; RA: retinoic acid; Shh: sonic hedgehog.

Figure 2

Schematic of three neural organogenesis approaches in vitro. (a) Stepwise, direct organization of region-specific or population-enriched organoids; (b) assemble and direct distinct organ-specific progenitor cells or stem cells to form specific morphogenesis organ; (c) assemble embryoid bodies for induction of multilayer organoids.