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.

Vascularization and Engraftment of Transplanted Human Cerebral Organoids in Mouse Cortex

“…In both the current study and the study by Mansour et al (2018) , organoids were grown in culture for 40–50 d from hESCs (approximately four weeks in Matrigel rotary condition) with largely dorsal forebrain specification, transplanting organoids of different maturity or of different regional specification by varying culture period or including different morphogen are worthwhile in future studies. Recent advancement allowed generation of region-specific neural organoids with features of neocortex ( Lee et al, 2017 ), telencephalon ( Watanabe et al, 2005 ), cerebellum ( Muguruma et al, 2015 ), neural tube ( Ranga et al, 2016 ), hippocampus ( Sakaguchi et al, 2015 ), and neural retina ( Kuwahara et al, 2015 ), among others ( Wei et al, 2017 ). These specialized neural organoids open the door for further testing of homotypic transplants wherein region-specific cerebral organoids are transplanted into the corresponding region in host brain.…”

The Application of Brain Organoid Technology in Stroke Research: Challenges and Prospects

“…Additionally, migration was faster in 2D cell culture with basement membrane extract ( Hakkinen et al, 2011 ). Brain organoids can integrate with the host tissue due to their self-renewal and self-organization after transplantation, which maintains the organoid cells in the brain ( Wei N. et al, 2017 ). 3D scaffolds can provide an environment for cell migration in stroke repair.…”

Organoid technology in female reproductive biomedicine

“…Upon transplantation, organoids have an intrinsic ability for self-renewal and self-organization, and can integrate into host tissue. Thus, stem cells or progenitor cells in organoids that have a higher survival rate and functional connections with the surrounding tissue in the host open a new and promising window for regenerative medicine [133]. Engraftment of endometrial organoids established from endometrium of TdTomato reporter mice under the kidney capsule of ovariectomized immunodeficient NOD/SCID/IL2Rgamma null (NSG) mice [4] led to the generation of an organized structure with glandular-type protuberances [4].…”