Abstract
In 1855, German biologist Rudolf Virchow stated that every cell arises from the preexisting cell through division. A single plant or human cell can produce a whole organism or different cell types. The property of a cell by which it can give rise to all cell types by repeated division and differentiation and produce the entire organism is known as totipotency. In the animal world, this property of cells is utilized for different purposes, viz., gene therapy, recombinant DNA technology, tissue engineering, as well as for the synthesis of biologicals including enzymes, vaccines, monoclonal antibodies, growth factors, biopesticides, etc. Animal cell culture technology requires a special and sterile condition, to maintain cell culture, which helps in reducing microbial contamination. Different types of equipment such as biosafety cabinets, incubators, inverted microscopes, well plates, and different cell lines such as HeLa and Chinese hamster ovary (CHO) cell lines, etc., are routinely used in cell culture laboratories. Synthetic and natural culture media are used for culturing different types of cells based on their nutritional requirements. This chapter discusses the techniques, types of equipments, and cell lines involved in animal cell culture. Further, it describes how cultured animal cells can be used for various applications especially in human health and the biomedical field.
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Abbreviations
- μL:
-
Microliter
- 3D:
-
Three dimensional
- AcMNPV:
-
Autographa californica multiple nuclear polyhedrosis virus
- ATCC:
-
American Type Culture Collection
- BHK:
-
Baby hamster kidney
- BMP:
-
Bone morphogenic protein
- BSL:
-
Biosafety level
- CHO:
-
Chinese hamster ovary
- DAPI:
-
Diamidino-2-phenylindole
- DMSO:
-
Dimethyl sulfoxide
- ds-RNA:
-
Double-stranded ribonucleic acid
- EGF:
-
Epidermal growth factor
- EPO:
-
Erythropoietin
- FACS:
-
Fluorescence-activated cell sorting
- HAMA:
-
Human anti-murine antibody
- HAT:
-
Hypoxanthine-aminopterin-thymidine
- HeLa:
-
Henrietta Lacks
- HEPA:
-
High-efficiency particulate air filter
- HEPES:
-
Hydroxyethylpiperazine ethane sulfonic acid
- HGPRT:
-
Hypoxanthine-guanine phosphoribosyltransferase
- HIV:
-
Human immunodeficiency virus
- HPACC:
-
Health Protection Agency Culture Collection
- HSCs:
-
Hematopoietic stem cells
- HuIFN-Beta:
-
Human interferon-beta
- IFN:
-
Interferon
- IFN-α:
-
Interferon-alpha
- IFN-β:
-
Interferon-beta
- IFN-γ:
-
Interferon-gamma
- IGF:
-
Insulin-like growth factor
- kDa:
-
Kilodaltons
- M:
-
Minute
- mAb:
-
Monoclonal antibodies
- moi:
-
Multiplicity of infection
- MOPS:
-
Morpholino propanesulfonic acid
- MRC-5:
-
Medical Research Council cell strain 5
- MS:
-
Multiple sclerosis
- NIH:
-
National Institute of Health
- PDGF:
-
Platelet-derived growth factor
- pfu:
-
Plaque-forming-units
- polyI:polyC:
-
Polyinosinic:polycytidylic acid
- SV40:
-
Simian vacuolating virus 40
- TGF:
-
Transforming growth factor
- t-PA:
-
Tissue plasminogen activator
- UV:
-
Ultraviolet
- VEGF:
-
Vascular endothelial growth factor
- WI:
-
Wistar Institute
References
Abraham RT, Weiss A (2004) Jurkat T cells and development of the T-cell receptor signalling paradigm. Nat Rev Immunol 4(4):301–308. https://doi.org/10.1038/nri1330
Anderson KP, Low M-AL, Lie YS, Keller G-A, Dinowitz M (1991) Endogenous origin of defective retroviruslike particles from a recombinant Chinese hamster ovary cell line. Virology 181(1):305–311. https://doi.org/10.1016/0042-6822(91)90496-X
Anson DS, Austen DEG, Brownlee GG (1985) Expression of active human clotting factor IX from recombinant DNA clones in mammalian cells. Nature 315(6021):683–685. https://doi.org/10.1038/315683a0
Arora M (2020) Cell culture media: a review. Mater Methods 2013(3):175. https://doi.org/10.13070/mm.en.3.175. www.labome.com/method/Cell-Culture-Media-A-Review.html
Astashkina A, Mann B, Grainger DW (2012) A critical evaluation of in vitro cell culture models for high-throughput drug screening and toxicity. Pharmacol Ther 134(1):82–106. https://doi.org/10.1016/j.pharmthera.2012.01.001
Bandurska K, Król I, Myga-Nowak M (2014) Interferons: between structure and function. Postepy Higieny I Medycyny Doswiadczalnej 68:428–440. https://doi.org/10.5604/17322693.1101229
Baricault L, Denariaz G, Houri JJ, Bouley C, Sapin C, Trugnan G (1995) Use of HT-29, a cultured human colon cancer cell line, to study the effect of fermented milks on colon cancer cell growth and differentiation. Carcinogenesis 16(2):245–252. https://doi.org/10.1093/carcin/16.2.245
Barnes D, Sato G (1980) Methods for growth of cultured cells in serum-free medium. Anal Biochem 102(2):255–270. https://doi.org/10.1016/0003-2697(80)90151-7
Berger M, Shankar V, Vafai A (2002) Therapeutic applications of monoclonal antibodies. Am J Med Sci 324(1):14–30. https://doi.org/10.1097/00000441-200207000-00004
Birch JR, Arathoon R (1990) Suspension culture of mammalian cells. Bioproc Technol 10:251–270
Bretton PR, Melamed MR, Fair WR, Cote RJ (1994) Detection of occult micrometastases in the bone marrow of patients with prostate carcinoma. Prostate 25(2):108–114
Brohem CA, Cardeal LBS, Tiago M, Soengas MS, Barros SBM, Maria-Engler SS (2011) Artificial skin in perspective: concepts and applications. Pigm Cell Melan Res 24(1):35–50. https://doi.org/10.1111/j.1755-148X.2010.00786.x
Chandler D, Bailey AS, Tatchell GM, Davidson G, Greaves J, Grant WP (2011) The development, regulation and use of biopesticides for integrated pest management. Philos Trans R Soc Lond Ser B Biol Sci 366(1573):1987–1998. https://doi.org/10.1098/rstb.2010.0390
Clark JM, Hirtenstein MD (1981) Optimizing culture conditions for the production of animal cells in microcarrier culture. Ann N Y Acad Sci 369:33–46. https://doi.org/10.1111/j.1749-6632.1981.tb14175.x
Clarke JH, Norman JA, Lavery E (1989) Some observations on contamination of animal cell cultures by the fungus Aspergillus fumigatus and suggested control measures. Cell Biol Int Rep 13(9):773–779. https://doi.org/10.1016/0309-1651(89)90054-4
Coté RJ (2001) Aseptic technique for cell culture. Curr Protoc Cell Biol Chapter 1:Unit 1.3. https://doi.org/10.1002/0471143030.cb0103s00
DiEdwardo CA, Petrosko P, Acarturk TO, DiMilla PA, LaFramboise WA, Johnson PC (1999) Muscle tissue engineering. Clin Plast Surg 26(4):647–656. ix–x
Eagle H (1955) Nutrition needs of mammalian cells in tissue culture. Science 122(3168):501–514. https://doi.org/10.1126/science.122.3168.501
Eagle H (1971) Buffer combinations for mammalian cell culture. Science 174(4008):500–503. https://doi.org/10.1126/science.174.4008.500
Ettinger A, Wittmann T (2014) Fluorescence live cell imaging. Methods Cell Biol 123:77–94. https://doi.org/10.1016/B978-0-12-420138-5.00005-7
Fuchs E (2012) The impact of cell culture on stem cell research. Cell Stem Cell 10(6):640–641. https://doi.org/10.1016/j.stem.2012.03.010
Fuchs E, Nowak JA (2008) Building epithelial tissues from skin stem cells. Cold Spring Harb Symp Quant Biol 73:333–350. https://doi.org/10.1101/sqb.2008.73.032
Geraghty RJ, Capes-Davis A, Davis JM, Downward J, Freshney RI, Knezevic I, Lovell-Badge R, Masters JRW, Meredith J, Stacey GN, Thraves P, Vias M, Cancer Research UK (2014) Guidelines for the use of cell lines in biomedical research. Br J Cancer 111(6):1021–1046. https://doi.org/10.1038/bjc.2014.166
Ghavim M, Abnous K, Arasteh F, Taghavi S, Nabavinia MS, Alibolandi M, Ramezani M (2017) High level expression of recombinant human growth hormone in Escherichia coli: crucial role of translation initiation region. Res Pharmaceut Sci 12(2):168–175. https://doi.org/10.4103/1735-5362.202462
Goliwas KF, Richter JR, Pruitt HC, Araysi LM, Anderson NR, Samant RS, Lobo-Ruppert SM, Berry JL, Frost AR (2017) Methods to evaluate cell growth, viability, and response to treatment in a tissue engineered breast cancer model. Sci Rep 7(1):14167. https://doi.org/10.1038/s41598-017-14326-8
Gordon J, Amini S, White MK (2013) General overview of neuronal cell culture. Methods Mol Biol 1078:1–8. https://doi.org/10.1007/978-1-62703-640-5_1
Graf BW, Boppart SA (2010) Imaging and analysis of three-dimensional cell culture models. Methods Mol Biol 591:211–227. https://doi.org/10.1007/978-1-60761-404-3_13
Ham RG, Puck TT (1962) A regulated incubator controlling CO2 concentration, humidity and temperature for use in animal cell culture. Proc Soc Exp Biol Med 111:67–71. https://doi.org/10.3181/00379727-111-27707
Hancock JF (1992) COS cell expression. Methods Mol Biol 8:153–158. https://doi.org/10.1385/0-89603-191-8:153
Harris AR, Peter L, Bellis J, Baum B, Kabla AJ, Charras GT (2012) Characterizing the mechanics of cultured cell monolayers. Proc Natl Acad Sci U S A 109(41):16449–16454. https://doi.org/10.1073/pnas.1213301109
Hatano A, Chiba H, Moesa HA, Taniguchi T, Nagaie S, Yamanegi K, Takai-Igarashi T, Tanaka H, Fujibuchi W (2011) CELLPEDIA: a repository for human cell information for cell studies and differentiation analyses. Database 2011:bar046. https://doi.org/10.1093/database/bar046
Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen C-J, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CDM, Silberman S, Dimitrijevic S, Fletcher JA (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21(23):4342–4349. https://doi.org/10.1200/JCO.2003.04.190
Heller E, Fuchs E (2015) Tissue patterning and cellular mechanics. J Cell Biol 211(2):219–231. https://doi.org/10.1083/jcb.201506106
Herman P, Pauwels K (2014) Biosafety recommendations on the handling of animal cell cultures. Anim Cell Cult 9:689–716. https://doi.org/10.1007/978-3-319-10320-4_22
Hitchcock T, Niklason L (2008) Lymphatic tissue engineering: progress and prospects. Ann N Y Acad Sci 1131:44–49. https://doi.org/10.1196/annals.1413.004
Howard D, Buttery LD, Shakesheff KM, Roberts SJ (2008) Tissue engineering: strategies, stem cells and scaffolds. J Anat 213(1):66–72. https://doi.org/10.1111/j.1469-7580.2008.00878.x
Hunt SMN, Pak SCO, Bridges MW, Gray PP, Sleigh MJ (1997) Chinese hamster ovary cells produce sufficient recombinant insulin-like growth factor I to support growth in serum-free medium. Serum-free growth of IGF-I-producing CHO cells. Cytotechnology 24(1):55–64. https://doi.org/10.1023/A:1007969502256
Inoue N, Takeuchi M, Ohashi H, Suzuki T (1995) The production of recombinant human erythropoietin. Biotechnol Annu Rev 1:297–313. https://doi.org/10.1016/s1387-2656(08)70055-3
Isaacs A, Lindenmann J (1957) Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci 147(927):258–267. https://doi.org/10.1098/rspb.1957.0048
Jedrzejczak-Silicka M (2017) Chapter 1: History of cell culture. In: Gowder SJ (ed) New insights into cell culture technology. IntechOpen, London. https://doi.org/10.5772/66905
Jordan I, Sandig V (2014) Matrix and backstage: cellular substrates for viral vaccines. Viruses 6(4):1672–1700. https://doi.org/10.3390/v6041672
Karpusas M, Whitty A, Runkel L, Hochman P (1998) The structure of human interferon-beta: implications for activity. Cell Mol Life Sci 54(11):1203–1216. https://doi.org/10.1007/s000180050248
Kaur G, Dufour JM (2012) Cell lines: valuable tools or useless artifacts. Spermatogenesis 2(1):1–5. https://doi.org/10.4161/spmg.19885
Kim JY, Kim Y-G, Lee GM (2012) CHO cells in biotechnology for production of recombinant proteins: current state and further potential. Appl Microbiol Biotechnol 93(3):917–930. https://doi.org/10.1007/s00253-011-3758-5
Kin T, Mirbolooki M, Lakey JRT (2007) 33—Design and implementation of a cell processing facility. In: Halberstadt C, Emerich D (eds) Cellular transplantation. Academic Press, New York, NY, pp 629–633. https://doi.org/10.1016/B978-012369415-7/50034-X. ISBN 9780123694157
Köhler G, Milstein C (1976) Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. Eur J Immunol 6(7):511–519. https://doi.org/10.1002/eji.1830060713
Kontsek P (1994) Human type I interferons: structure and function. Acta Virol 38(6):345–360
Lawn RM, Vehar GA (1986) The molecular genetics of hemophilia. Sci Am 254(3):48–54. https://doi.org/10.1038/scientificamerican0386-48
Li F, Vijayasankaran N, Shen AY, Kiss R, Amanullah A (2010) Cell culture processes for monoclonal antibody production. MAbs 2(5):466–479. https://doi.org/10.4161/mabs.2.5.12720
Lucey BP, Nelson-Rees WA, Hutchins GM (2009) Henrietta Lacks, HeLa cells, and cell culture contamination. Arch Pathol Lab Med 133(9):1463–1467. https://doi.org/10.1043/1543-2165-133.9.1463
Masters JR, Stacey GN (2007) Changing medium and passaging cell lines. Nat Protoc 2(9):2276–2284. https://doi.org/10.1038/nprot.2007.319
Morgan JF, Morton HJ, Parker RC (1950) Nutrition of animal cells in tissue culture; initial studies on a synthetic medium. Proc Soc Exp Biol Med 73(1):1–8. https://doi.org/10.3181/00379727-73-17557
Newsome BW, Ernstoff MS (2008) The clinical pharmacology of therapeutic monoclonal antibodies in the treatment of malignancy; have the magic bullets arrived? Br J Clin Pharmacol 66(1):6–19. https://doi.org/10.1111/j.1365-2125.2008.03187.x
Orlova NA, Kovnir SV, Vorobiev II, Gabibov AG, Vorobiev AI (2013) Blood clotting factor VIII: from evolution to therapy. Acta Nat 5(2):19–39
Pandey S (2010) Hybridoma technology for production of monoclonal antibodies. Int J Pharmaceut Sci Rev Res 1(2):88–94
Parray HA, Shukla S, Samal S, Shrivastava T, Ahmed S, Sharma C, Kumar R (2020) Hybridoma technology a versatile method for isolation of monoclonal antibodies, its applicability across species, limitations, advancement and future perspectives. Int Immunopharmacol 85:106639. https://doi.org/10.1016/j.intimp.2020.106639
Passmore JS, Lukey PT, Ress SR (2001) The human macrophage cell line U937 as in vitro model for selective evaluation of mycobacterial antigen-specific cytotoxic T-cell function. Immunology 102(2):146–156. https://doi.org/10.1046/j.1365-2567.2001.01164.x
Phelan K, May KM (2016) Mammalian cell tissue culture techniques. Curr Protoc Pharmacol 73(1):12.1.1–12.1.23. https://doi.org/10.1002/cpph.1
Rodrigues AF, Soares HR, Guerreiro MR, Alves PM, Coroadinha AS (2015) Viral vaccines and their manufacturing cell substrates: new trends and designs in modern vaccinology. Biotechnol J 10(9):1329–1344. https://doi.org/10.1002/biot.201400387
Samuel CE (2001) Antiviral actions of interferons. Clin Microbiol Rev 14(4):778–809. https://doi.org/10.1128/CMR.14.4.778-809.2001
Savan R, Ravichandran S, Collins JR, Sakai M, Young HA (2009) Structural conservation of interferon gamma among vertebrates. Cytokine Growth Factor Rev 20(2):115–124. https://doi.org/10.1016/j.cytogfr.2009.02.006
Sewell DL (1995) Laboratory-associated infections and biosafety. Clin Microbiol Rev 8(3):389–405. https://doi.org/10.1128/CMR.8.3.389
Stacey GN (2011) Cell culture contamination. Methods Mol Biol 731:79–91. https://doi.org/10.1007/978-1-61779-080-5_7
Stopak D, Harris AK (1982) Connective tissue morphogenesis by fibroblast traction: I. Tissue culture observations. Dev Biol 90(2):383–398. https://doi.org/10.1016/0012-1606(82)90388-8
Tomita M, Tsumoto K (2011) Hybridoma technologies for antibody production. Immunotherapy 3(3):371–380. https://doi.org/10.2217/imt.11.4
Valtink M, Engelmann K, Strauss O, Krüger R, Löliger C, Ventura AS, Richard G (1999) Physiological features of primary cultures and subcultures of human retinal pigment epithelial cells before and after cryopreservation for cell transplantation. Graefes Arch Clin Exp Ophthalmol 237(12):1001–1006. https://doi.org/10.1007/s004170050336
Vazin T, Freed WJ (2010) Human embryonic stem cells: derivation, culture, and differentiation: a review. Restor Neurol Neurosci 28(4):589–603. https://doi.org/10.3233/RNN-2010-0543
Verma A (2014) Chapter 12—Animal tissue culture: principles and applications. In: Verma AS, Singh A (eds) Animal biotechnology. Academic Press, pp 211–231. https://doi.org/10.1016/B978-0-12-416002-6.00012-2
Verma A, Verma M, Singh A (2020) Animal tissue culture principles and applications. Anim Biotechnol 2020:269–293. https://doi.org/10.1016/B978-0-12-811710-1.00012-4
Victorio CBL, Xu Y, Ng Q, Chow VTK, Chua KB (2014) Phenotypic and genotypic characteristics of novel mouse cell line (NIH/3T3)-adapted human enterovirus 71 strains (EV71:TLLm and EV71:TLLmv). PLoS One 9(3):e92719. https://doi.org/10.1371/journal.pone.0092719
Warnock JN, Merten O-W, Al-Rubeai M (2006) Cell culture processes for the production of viral vectors for gene therapy purposes. Cytotechnology 50(1–3):141–162. https://doi.org/10.1007/s10616-005-5507-z
Wesselschmidt RL, Schwartz PH (2011) The stem cell laboratory: design, equipment, and oversight. Methods Mol Biol 767:3–13. https://doi.org/10.1007/978-1-61779-201-4_1
Wilson JM (2005) Gendicine: the first commercial gene therapy product. Hum Gene Ther 16(9):1014–1015. https://doi.org/10.1089/hum.2005.16.1014
Yao T, Asayama Y (2017) Animal-cell culture media: history, characteristics, and current issues. Reprod Med Biol 16(2):99–117. https://doi.org/10.1002/rmb2.12024
Yee CM, Zak AJ, Hill BD, Wen F (2018) The coming age of insect cells for manufacturing and development of protein therapeutics. Ind Eng Chem Res 57(31):10061–10070. https://doi.org/10.1021/acs.iecr.8b00985
Yokoyama WM, Christensen M, Santos GD, Miller D, Ho J, Wu T, Dziegelewski M, Neethling FA (2013) Production of monoclonal antibodies. Curr Protoc Immunol 102(1):2.5.1–2.5.29. https://doi.org/10.1002/0471142735.im0205s102
Zhu MM, Mollet M, Hubert RS, Kyung YS, Zhang GG (2017) Industrial production of therapeutic proteins: cell lines, cell culture, and purification. In: Handbook of industrial chemistry and biotechnology, pp 1639–1669. https://doi.org/10.1007/978-3-319-52287-6_29
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Chandra, V., Tiwari, A., Pant, K.K., Bhatt, R. (2022). Animal Cell Culture: Basics and Applications. In: Verma, P. (eds) Industrial Microbiology and Biotechnology. Springer, Singapore. https://doi.org/10.1007/978-981-16-5214-1_24
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