Table 2.

Endothelial cell sources for tissue models.

Organ	Cell Source	EC Classification	Main Challenges	Evaluated LAM Expression	Tissue Chip Models with TEM
“Generic” EC	HUVEC	Continuous	Macrovascul-ature, not tissue-specific	• Expresses/upregulates key molecules	• (59) • (60) • (61)
	hMVEC	Continuous	Not tissue-specific	• Expresses/upregulates key molecules	• (62)
	BOEC	Continuous	Not tissue-specific, variable success rate for isolation and culture	• Expresses/upregulates key molecules	• None
	hiPSC: reviewed in Jang et al., 2019; Williams and Wu, 2019; Xu et al., 2019	Continuous	Not tissue-specific, immature phenotype	• Variable • Upregulates ICAM-1 • Fails to upregulate VCAM-1 (Orlova et al., 2014)	• (50) (adhesion only)
	hiPSC: cord blood-derived CD34+	Continuous	Not tissue specific	• Upregulates ICAM-1, ICAM-2, VCAM-1	• (63) (for brain)
	hiPSC (rEC): Lu et al., 2021b	Continuous	Not tissue specific	• Expresses PECAM-1 • Upregulates E-selectin	• None (proposed for future brain models)
	hiPSC: viEC	Continuous	Not tissue specific	• Did not evaluate	• (64) (for glomerulus)
BMEC	Immortalized Human (hCMEC/D3)	Continuous	Rapid de-differentiati-on	• Expresses/upregulates key molecules	• None
	Primary Human	Continuous	Difficult to isolate, rapid de-differentiation	• Expresses/upregulates key molecules	• (44) • (65)
	hiPSC (iBMEC): Lippmann et al., 2012	Continuous	Endothelial/epithelial hybrids	• No expression of E-selectin, P-selectin, ICAM-2, VCAM-1	• None
	hiPSC (EECM-BMEC): Nishihara et al., 2020	Continuous	Weaker barrier properties	• Expresses PECAM-1 • Upregulates P- selectin, E-selectin • Upregulates ICAM-1, ICAM-2, VCAM-1	• (66)
Lung EC	Primary Human (HMVEC-L, LMVEC, HLVEC, and HPMEC)	Continuous	Mix of blood and lymphatic ECs, genetically heterogenous, slow-growing, limited passages	• Upregulates E-selectin • Upregulates ICAM-1, VCAM-1	• (51) • (32) • (67)
	hiPSC: Taniguchi et al., 2020	Continuous	Immature phenotype	• Did not evaluate	• None
GEC	Primary Human	Fenestrated	Difficult to isolate and culture, limited lifespan	• Upregulates E-selectin (Cell Systems)	• None
LSEC	Immortalized Human (TMNK-1)	Continuous	Rapid dedifferentia-tion, chronically activated	• Upregulates key molecules	• None
	Primary Human (HLEC)	Fenestrated	Mix of human liver derived ECs (80% LSECs)	• Upregulates ICAM-1	• (34)
	hiPSC: Koui et al., 2017; Gage et al., 2020	Fenestrated	Not fully characterized	• Did not evaluate	• None

EC, endothelial cell; LAM, leukocyte adhesion molecule; TEM, transmigration; BMEC, brain microvascular endothelial cell; GEC, glomerular endothelial cell; LSEC, liver sinusoidal endothelial cell; HUVEC, human umbilical vein endothelial cell; hMVEC, human microvascular endothelial cell; BOEC, blood outgrowth endothelial cell; hiPSC, human induced pluripotent stem cell; rEC, EEF-reprogrammed Epi-iBMECs; viEC, vascular endothelial cell; hCMEC/D3, human cerebral microvascular endothelial cell; iBMEC, induced brain microvascular endothelial cell; EECM-BMEC, extended endothelial cell culture method brain microvascular endothelial cell; HMVEC-L, human microvascular endothelial cell-lung; LMVEC, lung microvascular endothelial cell; HLVEC, human lung vascular endothelial cell; HPMEC, human pulmonary microvascular endothelial cell; TMNK-1, immortalized human-liver endothelial cell line with SV40T and hTERT; HLEC, human liver-derived endothelial cell; PECAM-1, platelet endothelial cell adhesion molecule-1; ICAM-1, intercellular adhesion molecule-1; ICAM-2, intercellular adhesion molecule-2; VCAM-1, vascular cell adhesion molecule-1.