Current overview of induced pluripotent stem cell-based blood-brain barrier-on-a-chip

Figure 1 PRISMA flow chart of the study selection process applied in this systematic review. iPSC: Induced pluripotent stem cell.

Figure 2 Induced pluripotent stem cell differentiation process into induced pluripotent stem cell-derived brain microvascular endothelial-like cells for reconstruction of the blood-brain barrier-on-a-chip model. A: Percent analysis of cells and culture media used in induced pluripotent stem cell expansion and differentiation before blood-brain barrier (BBB)-on-a-chip reconstruction; B: Schematic summary of the main findings in this systematic review on the cells and culture conditions applied in the BBB-on-a-chip reconstruction process. Studies were grouped by similar device designs. AAc: Ascorbic acid; AC: Astrocyte; ACS-1024: Bone-induced pluripotent stem cell line; AGF: Astrocyte growth factor; AGM: Astrocyte growth medium; BC1: Lymphoma cell line; BDNF: Brain-derived neurotrophic factor; bFGF: Bovine fibroblast growth factor; BMM: Basement membrane matrix; bPPP: Basic platelet-poor plasma; D1: Day 1; D2: Day 2; D3: Day 3; D38: Day 38; D4: Day 4; D5: Day 5; D6: Day 6; D8: Day 8; D9: Day 9; db-cAMP1: 2’-O-Dibutyryladenosine-3’,5’-cyclic monophosphate; DMEM/F12: Dulbecco’s modified Eagle medium with F12; DPBS: Dulbecco’s phosphate-buffered saline; DX: Doxycycline; E8: Essential 8 medium; EC-/-: Human endothelial serum-free medium without retinoic acid + basic fibroblast growth factor; EC: Endothelial cell; EC+/+: Human endothelial serum-free medium with retinoic acid + basic fibroblast growth factor; ECM: Extracellular matrix; EGM-2MV: Microvascular endothelial cell growth medium-2; ESFM: Endothelial serum-free medium; FBS: Fetal bovine serum; FCS: Fetal calf serum; FGF2: Fibroblast growth factor 2; GDNF: Glial cell line-derived neurotrophic factor; GFP: Green fluorescent protein; GFR: Growth factor reduced; GM25256: Cell line of induced pluripotent stem cell derived from adult skin fibroblasts; GM6001: Broad spectrum MMP inhibitor; HBVP: Human brain vascular pericytes; HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; HESFM: Human endothelial serum-free medium; hFGF: Human fibroblast growth factor; hiPSC-EC: Human-induced pluripotent stem cell-derived endothelial cell; hPDS: Human serum from platelet-poor human plasma; hPDS: Platelet-poor plasma-derived human serum; HUVEC: Human umbilical vein endothelial cell; iBMECs: Induced pluripotent stem cell-derived brain microvascular endothelial cells; IMR90-C4: Induced pluripotent stem cell line; iPSCs: Induced pluripotent stem cells; LN: Laminin; ms1: Brain-derived neurotrophic factor + glial cell line-derived neurotrophic factor + ascorbic acid + 2’-O-Dibutyryladenosine-3’,5’-cyclic monophosphate; ms2: Primocin + glutamax + doxycycline + neurotrophin-3 + brain-derived neurotrophic factor + fetal calf serum; mTeSR1: Basal medium type for induced pluripotent stem cells; N2B27: Culture medium; NA: Not applied; NR: Not reported; NT3: Neurotrophin-3; P/S: Penicillin/streptomycin; PCs: Pluripotent cells; PM: Pericyte medium; RA: Retinoic acid; RA: Retinoic acid; RT: Room temperature; SFB: Serum-free medium; UM: Unconditioned medium; VEGF: Vascular endothelial growth factor; Y27632: Dihydrochloride inhibitor.