Table 1.

The impact of e-cigarette liquid exposure to various cell models (in vitro study).

	Type of Cells	Characteristic of E-Liquid	Action	Ref.
1.	NHBE cells	Base: PG:VG (50%/50%) Nicotine: 36 mg/mL Flavor: flavorless	Decreased: airway surface liquid hydration Increased: mucus viscosity	[114]
2.	NHBE cells	Base: PG:VG Nicotine: 24 mg/mL Flavor: “Tennessee Cured”	Decreased: cell viability Increased: oxidative stress	[120]
3.	NHBE cells	Base: PG:VG (55%/45%) Nicotine: none Flavors: three cinnamon flavors	Decreased: intracellular ATP levels Impaired: mitochondrial respiration and glycolysis	[106]
4.	NHBE cells	Base: VG 100% Nicotine: 1.1% Flavors: tobacco	Inhibited: epithelial ion transport beyond cystic fibrosis transmembrane conductance regulator	[121]
5.	NHBE cells	Base: unknown Nicotine 2.4% w/v Flavor: flavorless	Dysregulation of gene expression	[108]
6.	NHBE cells	Base: unknown Nicotine: 24 mg per cartridge Flavors: menthol, tobacco	Decreased: expression of genes involved in cilia assembly and movement Increased: expression of genes involved in oxidative and xenobiotic stress pathways and a marker of reactive oxygen species production	[122]
7.	NHBE cells	Base: unknown Nicotine: 36 mg/mL Flavor: flavorless	Decreased: expression of FOXJ1 and KCNMA1 Increased: interleukin (IL)-6 and IL-8 release Impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance	[100]
8.	NHBE cells	Base: unknown Nicotine: 16 mg/mL Flavor: flavorless	Alterations in cellular glycerophopholipid biosynthesis, cytochrome P450 function, retinoid metabolism, and nicotine catabolism	[109]
9.	NHBE cells	E-cigarette liquid diluted to 100 μM by nicotine	Alters the metabolome	[104]
10.	NHBE cells THP-1 macrophages	Base: PG:VG (70%:30%) Nicotine: 18 mg/mL Flavors: three apple flavors	Decreased: efferocytosis, TNF-α, IL-6, IP-10, MIP-1α and MIP-1β release Increased: necrosis and apoptosis	[123]
11.	NHBE cells	Base: PG:VG (50%/50%) Nicotine: 24 mg/mL Flavor: flavorless	Increased: IL-8 release in response to infection	[111]
12.	NHBE cells—H292 cell line	Base: PG 100% Nicotine: 24 mg/mL Flavors: tobacco, piña colada, menthol, coffee and strawberry	Decreased: metabolic activity and cell viability Increased: interleukin [IL]-1β, IL-6, IL-10, CXCL1, CXCL2 and CXCL10 release	[124]
13.	Immortalized NHBE cell line—CL-1548	Base: unknown Nicotine: none Flavor: flavorless	Decreased: ciliated, mucus-producing and club cells [phenotypic changes]	[107]
14.	NHBE 3D cell cultures	Base: unknown Nicotine: 7μg/mL equi- nicotine units Flavor: flavorless	Decreased: cystic fibrosis transmembrane conductance regulator and the epithelial sodium channel function, which regulate fluid homeostasis in the lung	[115]
15.	Human lung carcinoma A549 cells	Base: PG:VG (50%/50%) VG 100%, PG 100% Nicotine: 18 mg/mL Flavor: flavorless	Decreased: cell viability	[113]
16.	A549 cells	Base: unknown Nicotine: 18 mg/mL Flavor: strawberry	Decreased: cell viability	[125]
17.	A549 cells	Base: unknown Nicotine: 24 mg/mL Flavor: tobacco	Increased: pneumococcal adhesion to airway cells	[126]
18.	Human lung adenocarcinoma cells—A549 and NCI-H441	Base: PG:VG (50%/50%) Nicotine: 18 mg/mL Flavors: cinnamon, tobacco, menthol	Decreased: cell viability Increased: IL-8 release	[127]
19.	Human-derived bronchial epithelial cell lines—BEAS-2B, IB3-1, C38 and CALU-3; Macrophage cell lines—J774, a mouse macrophage and THP-1 a monocyte-derived macrophage; human-derived fibroblast cell line—Wi-38	Base: PG:VG Nicotine: 0.8–16 mg/mL Flavors: flavorless, cherry, tobacco, crisp mint, menthol, apple, coffee, vanilla, strawberry	Decreased: cell viability	[128]
20.	Human-induced pluripotent stem cell-derived endothelial cells [iPSC-ECs]	Base: PG:VG (50%/50%, 80%/20%), VG 100% Nicotine: 6 and 18 mg/mL Flavors: sweet tobacco with undertones of caramel, vanilla, tobacco, sweet, cinnamon, menthol	Decreased: cell viability Increased: ROS levels, caspase 3/7 activity Promoted: low-density lipoprotein uptake, activation of oxidative stress-related pathway, impaired tube formation and migration	[129]
21.	Human pulmonary fibroblasts [hPFs]; A549 lung epithelial cells; pluripotent human embryonic stem cells [hESCs]	Base: PG:VG, VG, unknown Nicotine: 6–24 mg/mL Flavors: fruit, tobacco, mint, chocolate, vanilla, caramel, candy, coffee, cinnamon, creamy	Decreased: cell viability	[130]
22.	Human airway epithelium cells	Base: PG:VG Nicotine: 2.4% Flavor: tobacco	Morphologic differences in secretory function	[131]
23.	Lung epithelial cell line [CALU3]	Base: PG:VG (70%/30%, 55%/45%) Nicotine: 12 mg/mL Flavors: Captain Black Cigar, Peanut Butter Cookie, T-bone, Popcorn, Black Licorice, Energon [orange energy drink], Vanilla Tobacco, Banana Pudding [Southern Style], Kola, Hot Cinnamon Candies, Menthol Tobacco, Solid Menthol, Peanut Butter Cookies, Banana Pudding, and Hot Cinnamon Candies	Decreased: cell viability	[132]
24.	Human umbilical vein endothelial cells [HUVECs]	Base: PG:VG Nicotine: 6–24 mg/mL Flavors: tobacco, menthol, fruit	Decreased: cell viability Alterations in cell morphology	[133]
25.	Human lung fibroblasts [HFL-1]	Base: unknown Nicotine: 16 mg/mL Flavor: tobacco	Decreased: stability of electron transport chain complex IV subunit Increased: levels of mitochondrial ROS, nuclear DNA fragmentation, IL-8 and IL-6 release	[134]
26.	Neutrophils	Base: unknown Nicotine: 16, 24 mg/mL Flavor: tobacco	Increased: CD11b and CD66b expression, MMP-9 and CXCL8 release, NE and MMP-9 activity, p38 MAPK activation	[135]
27.	Human bronchial airway epithelial cells [H292]; human fetal lung fibroblasts [HFL1]	Base: PG:VG Nicotine: 16 mg/mL Flavors: tobacco, menthol fruit, cinnamon, candy	Decreased: cell viafbility Increased: IL-6 and IL-8 release, stress and morphological change	[98]
28.	Human Periodontal Ligament Fibroblasts	Base: PG 100% Nicotine: final concentration 10 µg/mL Flavors: hazelnut, lime, menthol	Decreased: cell viability	[136]
29.	ATII cells	Base: unknown Nicotine: 24 mg/mL Flavor: flavorless	Increased: IL-8 levels, DNA damage and apoptosis	[110]
30.	Mouse vascular endothelial cell line bEnd.3; Mouse primary brain microvascular endothelial cells	Base: unknown Nicotine: 24 mg/mL Flavor: flavorless	Increased: mitochondrial depolarization, transmembrane iron exporter Slc40a1 (crucial to maintain cellular iron and redox homeostasis) and porphyrin importer Abcb6 (linked to accelerated atherosclerosis)	[112]
31.	NHBR cell line BEAS-2B; human bronchial urothelial cell line UROtsa	Base; PG:VG (50%/50%) Nicotine: 24 mg/mL Flavor: flavorless	Increased: mutational susceptibility and tumorigenic transformation	[75]
32.	Human epithelial cells—human keratinocytes (HaCaTs); Human lung alveolar type II epithelial cells (A549 cells); Alveolar macrophages (AMs) Human polymorphonuclear leukocytes (hPMNs)	Base: PG:VG, PG, VG Nicotine: 8, 24 mg/mL Flavors: flavorless, Treasury, Highlander Grog, California Blues, Pure smoke	Decreased: antimicrobial activity against Staphylococcus aureus	[137]
33.	Normal epithelial cells (HaCat–a spontaneously transformed immortal keratinocyte cell line); Head and neck squamous cell carcinoma (HNSCC) cell lines (UMSCC10B—derived from a metastatic lymph node, HN30—derived from a primary laryngeal tumor)	Base: PG:VG (70%/30%) Nicotine: 12 mg/mL Flavors: “Classic Tobacco”, “Red American Tobacco”	Decreased: cell viability Increased: apoptosis and necrosis, DNA strand breaks	[138]
34.	Human osteosarcoma cell lines Saos-2 and MG-63	Base: PG/VG (50%/50%) Nicotine: 24 mg/mL Flavors: flavorless, watermelon, mango, mixed fruits, coffee, apple pie, menthol and watermelon, menthol, hot cinnamon, menthol and cinnamon	Decreased: cell viability Increased: collagen type I protein expression	[139]
35.	Normal human tracheobronchial epithelial cells (NHTE cells)	Base: unknown Nicotine: 18 mg/mL Flavor: tobacco	Increased: IL-6 release Promoted: human rhinovirus (HRV) infection	[101]
36.	Monocytic cells from human pleural tissue—U937; Human monocyte-macrophage cell line (mature monocytes-macrophages)—Mono Mac 6	Base: unknown Nicotine: none Flavors: Strawberry Zing, Café Latte, Pineapple Coconut, Cinnamon Roll, Fruit Swirl, Mega Melons, Mystery Mix (menthol flavor), American Tobacco, Grape Vape, Very Berry, and Mixed Flavors	Decreased: cell viability Increased: IL-8 secretion, oxidative stress (ROS level)	[105]
37.	Alveolar macrophages; THP-1 macrophages	Base: PG:VG (50%:50%) Nicotine: 36 mg/mL Flavor: flavorless	Decreased: cell viability	[99]