Cellular complexity in brain organoids: Current progress and unsolved issues

Abed Al Fatah Mansour, Simon T. Schafer, Fred H. Gage*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations


Brain organoids are three-dimensional neural aggregates derived from pluripotent stem cells through self-organization and recapitulate architectural and cellular aspects of certain brain regions. Brain organoids are currently a highly exciting area of research that includes the study of human brain development, function, and dysfunction in unprecedented ways. In this Review, we discuss recent discoveries related to the generation of brain organoids that resemble diverse brain regions. We provide an overview of the strategies to complement these primarily neuroectodermal models with cell types of non-neuronal origin, such as vasculature and immune cells. Recent transplantation approaches aiming to achieve higher cellular complexity and long-term survival of these models will then be discussed. We conclude by highlighting unresolved key questions and future directions in this exciting area of human brain organogenesis.

Original languageAmerican English
Pages (from-to)32-39
Number of pages8
JournalSeminars in Cell and Developmental Biology
StatePublished - Mar 2021
Externally publishedYes

Bibliographical note

Funding Information:
We thank members of the Gage laboratory for helpful discussions, Mary Lynn Gage for editorial comments, and Beth Coyne for administrative assistance. This work was supported by the AHA-Allen Initiative in Brain Health and Cognitive Impairment award made jointly through the American Heart Association and The Paul G. Allen Frontiers Group : ( 19PABH134610000 ), The Paul G Allen Family Foundation, Bob and Mary Jane Engman, The Leona M and Harry B Helmsley Charitable Trust Grant ( 2017-PG-MED001 ), Annette C Merle-Smith, The G Harold and Leila Y Mathers Foundation, JPB Foundation, Ray and Dagmar Dolby Family Fund, and the Grace Foundation for F.H.G. A.A.M received funding from the EMBO Postdoctoral Long-term Fellowship ( ALTF 1214-2014 ) and is currently supported by the Human Frontiers Science Program (HFSP Long-Term Fellowship- LT001074/2015 ); S.T.S was supported by a fellowship from the German Research Foundation (DFG) and is currently supported by the NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Leichtung Family Investigator). We apologize to those whose work was not cited owing to space constraints.

Publisher Copyright:
© 2020 Elsevier Ltd


  • Brain organoids
  • Cerebral organoids
  • Microglia
  • Pluripotent stem cells
  • Self-organization
  • Transplantation
  • Vascularization


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