# Neuroinflammatory In Vitro Cell Culture Models and the Potential Applications for Neurological Disorders

**Authors:** Ye Peng, Shifeng Chu, Yantao Yang, Zhao Zhang, Zongran Pang, Naihong Chen

PMC · DOI: 10.3389/fphar.2021.671734 · Frontiers in Pharmacology · 2021-04-23

## TL;DR

This review discusses in vitro cell culture models for studying neuroinflammation and their potential in neurological disorder research and drug screening.

## Contribution

The paper highlights the advantages and limitations of 2D and 3D cell culture models for mimicking the blood-brain barrier in neuroinflammatory conditions.

## Key findings

- 2D co-culture models are practical but lack the complexity of in vivo environments.
- 3D models, such as organs-on-chips, better replicate the BBB microenvironment and show promise for drug screening.
- Immortalized cell lines like PC12, SH-SY5Y, and BV2 are commonly used in neuroinflammation studies.

## Abstract

Cell cultures are used in pharmaceutical, medical and biological sciences. Due to the ethical and cost limitations of in vivo models, the replaceable cell model that is more closely related to the characteristics of organisms, which has broad prospects and can be used for high-throughput drug screening is urgent. Neuronal and glial cell models have been widely used in the researches of neurological disorders. And the current researches on neuroinflammation contributes to blood-brain barrier (BBB) damage. In this review, we describe the features of healthy and inflamed BBB and summarize the main immortalized cell lines of the central nervous system (PC12, SH-SY5Y, BV2, HA, and HBMEC et al.) and their use in the anti-inflammatory potential of neurological disorders. Especially, different co-culture models of neuroinflammatory, in association with immune cells in both 2D and 3D models are discussed in this review. In summary, 2D co-culture is easily practicable and economical but cannot fully reproduce the microenvironment in vivo. While 3D models called organs-on-chips or biochips are the most recent and very promising approach, which made possible by bioengineering and biotechnological improvements and more accurately mimic the BBB microenvironment.

## Full-text entities

- **Genes:** OCLN (occludin) [NCBI Gene 100506658] {aka BLCPMG, PPP1R115, PTORCH1}, Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}, Lgals3 (lectin, galactose binding, soluble 3) [NCBI Gene 16854] {aka GBP, L-34, Mac-2, gal3}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, CLDN5 (claudin 5) [NCBI Gene 7122] {aka AWAL, BEC1, CPETRL1, TMDVCF, TMVCF}, App (amyloid beta precursor protein) [NCBI Gene 54226] {aka Abeta}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, SLC7A6 (solute carrier family 7 member 6) [NCBI Gene 9057] {aka LAT-2, LAT3, y+LAT-2}, Csf1r (colony stimulating factor 1 receptor) [NCBI Gene 307403] {aka CSF-1-R, CSF-1R, M-CSF-R, c-fms, mrfms}, Csf1r (colony stimulating factor 1 receptor) [NCBI Gene 12978] {aka CD115, CSF-1R, Csfmr, Fim-2, Fim2, Fms}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, P2rx1 (purinergic receptor P2X, ligand-gated ion channel, 1) [NCBI Gene 18436] {aka P2x, Pdcd3, RP-2}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Abcc1 (ATP-binding cassette, sub-family C member 1) [NCBI Gene 17250] {aka Abcc1a, Abcc1b, MRP, Mdrap, Mrp1}, Lamp2 (lysosomal-associated membrane protein 2) [NCBI Gene 16784] {aka CD107b, LGP-B, Lamp II, Lamp-2, Lamp-2a, Lamp-2b}, Ngf (nerve growth factor) [NCBI Gene 310738] {aka Ngfb, beta-NGF}, Slc2a1 (solute carrier family 2 (facilitated glucose transporter), member 1) [NCBI Gene 20525] {aka GT1, Glut-1, Glut1, M100200, Rgsc200}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Mmp3 (matrix metallopeptidase 3) [NCBI Gene 17392] {aka EMS-2, MMP-3, SL-1, SLN-1, SLN1, STR-1}, Mmp9 (matrix metallopeptidase 9) [NCBI Gene 17395] {aka B/MMP9, Clg4b, Gel B, MMP-9, pro-MMP-9}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, TAS2R62P (taste 2 receptor member 62, pseudogene) [NCBI Gene 338399] {aka PS1, T2R62, TAS2R62}, DBH (dopamine beta-hydroxylase) [NCBI Gene 1621] {aka DBM, ORTHYP1}, Abcb1b (ATP-binding cassette, sub-family B member 1B) [NCBI Gene 24646] {aka Abcb1, Mdr1, Pgy1, Pgy2, mdr1b}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, CASK (calcium/calmodulin dependent serine protein kinase) [NCBI Gene 8573] {aka CAGH39, CAMGUK, CMG, FGS4, LIN2, MICPCH}
- **Diseases:** Cerebral edema (MESH:D001929), ischemic stroke (MESH:D002544), PD (MESH:D010300), edema (MESH:D004487), cancer (MESH:D009369), neurotoxicity (MESH:D020258), genetic defects (MESH:D030342), epilepsy (MESH:D004827), Neuroblastoma (MESH:D009447), CNS disease (MESH:D002493), SCI (MESH:D013119), ischemic (MESH:D002545), CNS inflammation (MESH:D007249), malnutrition (MESH:D044342), Neuroinflammatory (MESH:D000090862), AD (MESH:D000544), Brain inflammation (MESH:D004660), cytotoxic (MESH:D064420), neuronal damage (MESH:D009410), epilepticus (MESH:D013226), stroke (MESH:D020521), ischemia (MESH:D007511), ALS (MESH:D000690), Neurological Disorders (MESH:D009461), system (MESH:D015619), neurological disease (MESH:D020271), hypoxia (MESH:D000860), -brain-barrier (BBB) dysfunction (MESH:C536830), degenerative diseases of the CNS (MESH:D019636), traumatic diseases (MESH:D004194), adrenal medulla tumor (MESH:D000310), synapses damage (MESH:D020263), TBI (MESH:D000070642), glioma (MESH:D005910), nervous system diseases (MESH:D009422), middle cerebral artery occlusion (MESH:D020244)
- **Species:** Sus scrofa (pig, species) [taxon 9823], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Bos taurus (bovine, species) [taxon 9913], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** P301S
- **Cell lines:** U251 — Homo sapiens (Human), Astrocytoma, Cancer cell line (CVCL_0021), HCMEC/D3 — Homo sapiens (Human), Transformed cell line (CVCL_U985), HT22 — Mus musculus (Mouse), Transformed cell line (CVCL_0321), SIM — Homo sapiens (Human), Ewing sarcoma, Cancer cell line (CVCL_0097), HBMEC — Homo sapiens (Human), Transformed cell line (CVCL_0307), RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), stem cell — Homo sapiens (Human), Somatic stem cell (CVCL_AS77), iPSC — Gallus gallus (Chicken), Induced pluripotent stem cell (CVCL_YE48), BV2 — Mus musculus (Mouse), Transformed cell line (CVCL_0182), HA — Helicoverpa armigera (Cotton bollworm), Spontaneously immortalized cell line (CVCL_Z978), N2a — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_0470), b.End3 — Mus musculus (Mouse), Transformed cell line (CVCL_0170), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), Microglia — Homo sapiens (Human), Transformed cell line (CVCL_II76), SK-N-SH — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0531), TM- — Homo sapiens (Human), Transformed cell line (CVCL_E853), BBB — Rattus norvegicus (Rat), Conditionally immortalized cell line (CVCL_LH99), C8-D1A — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_6379), N9 — Mus musculus (Mouse), Transformed cell line (CVCL_0452), End3 — Homo sapiens (Human), Somatic stem cell (CVCL_WG35), N11 — Mus musculus (Mouse), Transformed cell line (CVCL_D426)

## Full text

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## Figures

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## References

129 references — full list in the complete paper: https://tomesphere.com/paper/PMC8103160/full.md

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Source: https://tomesphere.com/paper/PMC8103160