Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids.
Cell Stem Cell
; 31(6): 818-833.e11, 2024 Jun 06.
Article
em En
| MEDLINE
| ID: mdl-38754427
ABSTRACT
The human blood-brain barrier (hBBB) is a highly specialized structure that regulates passage across blood and central nervous system (CNS) compartments. Despite its critical physiological role, there are no reliable in vitro models that can mimic hBBB development and function. Here, we constructed hBBB assembloids from brain and blood vessel organoids derived from human pluripotent stem cells. We validated the acquisition of blood-brain barrier (BBB)-specific molecular, cellular, transcriptomic, and functional characteristics and uncovered an extensive neuro-vascular crosstalk with a spatial pattern within hBBB assembloids. When we used patient-derived hBBB assembloids to model cerebral cavernous malformations (CCMs), we found that these assembloids recapitulated the cavernoma anatomy and BBB breakdown observed in patients. Upon comparison of phenotypes and transcriptome between patient-derived hBBB assembloids and primary human cavernoma tissues, we uncovered CCM-related molecular and cellular alterations. Taken together, we report hBBB assembloids that mimic the core properties of the hBBB and identify a potentially underlying cause of CCMs.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Barreira Hematoencefálica
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Organoides
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Hemangioma Cavernoso do Sistema Nervoso Central
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Células-Tronco Pluripotentes
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article