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Blood-vessel-on-chip to study vascular malformations caused by PIK3CA mutations

Researchers at the University of North Carolina have created a model that mimics vascular malformations (VMs) that are specifically caused by a mutation of PIK3CA.

The researchers created a microfluidic model of these VMs using human cells that have the mutated gene. They found that the abnormal blood vessels in their model closely resemble the clinical features of VMs in patients. They also discovered that certain signaling pathways (Rac1/PAK, MEK/ERK, and mTORC1/2) are involved in the development of these VMs.

The researchers tested two different drugs, rapamycin, and alpelisib to see which could stop the vessels’ abnormal growth. They found that inhibiting PAK, MEK1/2, and mTORC1/2 was effective in reducing abnormal growth while inhibiting mTORC1 alone caused hyperbranching.

Their study was successful, and they plan to replicate their findings in tissues from vascular malformation patients, especially those who don’t have the PIK3CA mutation or clear genetic information. Their model could be used to test novel drugs to perform synergistic drug studies.


  1. Aw WY, Cho C, Wang H, et al. Microphysiological model of PIK3CA-driven vascular malformations reveals a role of dysregulated Rac1 and mTORC1/2 in lesion formation. Science Advances. 2023;9(7). doi:
  2. How a New Blood-Vessel-on-a-Chip Can Help Researchers Further Understand Vascular Malformations | Newsroom. Newsroom. Published February 24, 2023. Accessed February 28, 2023.

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