Modelling blood-brain barrier and cerebral cavernous malformations with organoids
2024
Cincinnati Children's Hospital Medical Center, Cincinnati, USA(1)
Mayo Clinic College of Medicine and Science, Rochester, USA(2)
University of California, San Diego, USA(3)
Mayo Clinic College of Medicine and Science, Rochester, USA(2)
University of California, San Diego, USA(3)
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, hBBB assembloids were constructed from brain and blood vessel organoids derived from human pluripotent stem cells. The acquisition of blood-brain barrier (BBB)-specific molecular, cellular, transcriptomic, and functional characteristics was validated and an extensive neuro-vascular crosstalk with a spatial pattern within hBBB assembloids was discovered. Using patient-derived hBBB assembloids to model cerebral cavernous malformations (CCMs), it could be 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, CCM-related molecular and cellular alterations were uncovered. Taken together, hBBB assembloids that mimic the core properties of the hBBB were reported and a potentially underlying cause of CCMs was identified.
Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids
Ziyuan Guo(1), L. Frank Huang(2), Sheng Zhong(3)
Added on: 06-24-2024
[1] https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00146-2
