Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies

DOI: 10.1038/s41467-019-10588-0

Authors: Tae-Eun Park; Nur Mustafaoglu; Anna Herland; Ryan Hasselkus; Robert Mannix; Edward A. FitzGerald; Rachelle Prantil-Baun; Alexander Watters; Olivier Henry; Maximilian Benz; Henry Sanchez; Heather J. McCrea; Liliana Christova Goumnerova; Hannah W. Song; Sean P. Palecek; Eric Shusta; Donald E. Ingber

Step 1: iPSC/ESC maintainance

day 0 ~ 3

culture “adherent” human PSC in “mTeSR” for “3” days. For ECM, use “Matrigel” at “N/A” “N/A”. Medium should be changed once in “3” days.

Step 2: endothelial 1

day 3 ~ 9

culture “adherent” human PSC in “DMEM/F12” for “6” days. For ECM, use “Matrigel” at “N/A” “N/A”. Medium should contain factors shown in the following table, and should be changed once in “6” days.

Ideally, “EC” should be obtained at the end of culture. Ideally, “NPC” should be obtained at the end of culture.

Step 3: endothelial 2

day 9 ~ 11

culture “adherent” human PSC in “endothelial cell medium” for “2” days. For ECM, use “Matrigel” at “N/A” “N/A”. Medium should contain factors shown in the following table, and should be changed once in “2” days.

Ideally, “EC” should express “CDH5”, “PECAM1”, “GLUT-1”, “P-gp”, “VEGF”, “Wnt7a”, “ZO-1”, “Claudin-5”, “HIF1A” at the end of culture.