Abstract
Programmed cell death (apoptosis and autophagy) in cell cultures is considered an important problem to be dealt with as it affects the viable cell concentration and the product quality. This chapter describes various strategies employed to confront and prevent programmed cell death in biotechnologically important mammalian cell lines, mainly Chinese Hamster Ovary (CHO) cells, with special importance to the genetic manipulation of cells for anti-apoptosis and anti-autophagic engineering.
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References
Adamson L, Walum E (2007) Insulin and IGF-1 mediated inhibition of apoptosis in CHO cells grown in suspension in a protein-free medium. Altern Lab Anim 35:349–352
Akar U, Chaves-Reyez A, Barria M et al (2008) Silencing of Bcl-2 expression by small Interfering RNA induces autophagic cell death in MCF-7 breast cancer cells. Autophagy 4:669–679
Al-Rubeai M, Singh RP (1998) Apoptosis in cell culture. Curr Opin Biotechnol 9:152–156
Al-Rubeai M, Singh RP, Goldman MH et al (1995) Death mechanisms of animal cells in conditions of intensive agitation. Biotechnol Bioeng 45:463–472
Alvarez B, Garrido E, Garcia-Sanz JA et al (2003) Phosphoinositide 3-kinase activation regulates cell division time by coordinated control of cell mass and cell cycle progression rate. J Biol Chem 278:26466–26473
Arden N, Betenbaugh MJ (2004) Life and death in mammalian cell culture: strategies for apoptosis inhibition. Trends Biotechnol 22:174–180
Arden N, Ahn SH, Vaz W et al (2007a) Chemical caspase inhibitors enhance cell culture viabilities and protein titer. Biotechnol Prog 23:506–511
Arden N, Majors BS, Ahn SH et al (2007b) Inhibiting the apoptosis pathway using MDM2 in mammalian cell cultures. Biotechnol Bioeng 97:601–614
Arico S, Petiot A, Bauvy C et al (2001) The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway. J Biol Chem 276:35243–35246
Blommaart EF, Luiken JJ, Blommaart PJ et al (1995) Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J Biol Chem 270:2320–2326
Blommaart EF, Krause U, Schellens JP et al (1997) The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur J Biochem 243:240–246
Bowen ID, Lockshin RA (1981) Cell death in biology and pathology. Chapman and Hall, London
Brown EJ, Schreiber SL (1996) A signaling pathway to translational control. Cell 86:517–520
Buja LM, Eigenbrodt ML, Eigenbrodt EH (1993) Apoptosis and necrosis. Basic types and mechanisms of cell death. Arch Pathol Lab Med 117:1208–1214
Bursch W (2001) The autophagosomal-lysosomal compartment in programmed cell death. Cell Death Differ 8:569–581
Chang KH, Kim KS, Kim JH (1999) N-acetylcysteine increases the biosynthesis of recombinant EPO in apoptotic Chinese hamster ovary cells. Free Radic Res 30:85–91
Cheng EH, Levine B, Boise LH et al (1996) Bax-independent inhibition of apoptosis by Bcl-xL. Nature 379:554–556
Chiang GG, Sisk WP (2005) Bcl-x(L) mediates increased production of humanized monoclonal antibodies in Chinese hamster ovary cells. Biotechnol Bioeng 91:779–792
Choi SS, Rhee WJ, Park TH (2005) Beneficial effect of silkworm hemolymph on a CHO cell system: Inhibition of apoptosis and increase of EPO production. Biotechnol Bioeng 91:793–800
Choi SS, RheeWJ KEJ, Kim EJ et al (2006) Enhancement of recombinant protein production in Chinese hamster ovary cells through anti-apoptosis engineering using 30Kc6 gene. Biotechnol Bioeng 95:459–467
Chowdhury I, Tharakan B, Bhat GK (2008) Caspases–An update. Comp Biochem Physiol B. doi:10.1016/j.cbpb.2008.05.010.
Cohen GM (1997) Caspases: The executioners of apoptosis. Biochem J 326:1–16
Cotter TG, Al-Rubeai M (1995) Cell death (apoptosis) in cell culture systems. Trends Biotechnol 13:150–155
Coultas L, Strasser A (2003) The role of the Bcl-2 protein family in cancer. Semin Cancer Biol 13:115–123
Crea F, Sarti D, Falciani F et al (2006) Over-expression of hTERT in CHO K1 results in decreased apoptosis and reduced serum dependency. J Biotechnol 121:109–123
D’Ambrosio C, Valentinis B, Prisco M et al (1997) Protective effect of the insulin-like growth factor I receptor on apoptosis induced by okadaic acid. Cancer Res 57:3264–3271
deZengotita VM, Miller WM, Aunins JG et al (2000) Phosphate feeding improves high-cell-concentration NS0 myeloma culture performance for monoclonal antibody production. Biotechnol Bioeng 69:566–576
Dickens M, Rogers JS, Cavanagh J et al (1997) A cytoplasmic inhibitor of the JNK signal transduction pathway. Science 277:693–696
Earnshaw WC, Martinsm LM, Kaufmann SH (1999) Mammalian caspases: Structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68:383–424
Farrow SN, Brown R (1996) New members of the Bcl-2 family and their protein partners. Curr Opin Genet Dev 6:45–49
Feng Z, Zhang H, Levine AJ et al (2005) The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci USA 102:8204–8209
Feng W, Huang S, Wu H et al (2007) Molecular basis of Bcl-xL’s target recognition versatility revealed by the structure of Bcl-xL in complex with the BH3 domain of Beclin-1. J Mol Biol 372:223–235
Figueroa B Jr, Sauerwald TM, Mastrangelo AJ et al (2001) Comparison of Bcl-2 to a Bcl-2 deletion mutant for mammalian cells exposed to culture insults. Biotechnol Bioeng 73:211–222
Figueroa B Jr, Sauerwald TM, Oyler GA et al (2003) A comparison of the properties of a Bcl-xL variant to the wild-type anti-apoptosis inhibitor in mammalian cell cultures. Metab Eng 5:230–245
Figueroa B Jr, Chen S, Oyler GA et al (2004) Aven and Bcl-xL enhance protection against apoptosis for mammalian cells exposed to various culture conditions. Biotechnol Bioeng 85:589–600
Figueroa B Jr, Ailor E, Osborne D et al (2007) Enhanced cell culture performance using inducible anti-apoptotic genes E1B–19 K and Aven in the production of a monoclonal antibody with Chinese hamster ovary cells. Biotechnol Bioeng 97:877–892
Fuertes G, Martin De Llano JJ, Villarroya A et al (2003) Changes in the proteolytic activities of proteasomes and lysosomes in human fibroblasts produced by serum withdrawal, amino-acid deprivation and confluent conditions. Biochem J 375:75–86
Fulda S, Debatin KM (2006) Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25:4798–4811
Goldman MH, James DC, Ison AP et al (1997) Monitoring proteolysis of recombinant human interferon-γ during batch culture of Chinese hamster ovary cells. Cytotechnology 23:103–111
Goswami J, Sinskey AJ, Steller H et al (1999) Apoptosis in batch cultures of Chinese hamster ovary cells. Biotechnol Bioeng 62:632–640
Gozuacik D, Kimchi A (2004) Autophagy as a cell death and tumor suppressor mechanism. Oncogene 23:2891–2906
Harris MH, Thompson CB (2000) The role of the bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ 7:1182–1191
Hay N, Sonenberg N (2004) Upstream and downstream of mTOR. Genes Dev 18:1926–1945
Hwang SO, Lee GM (2008a) Autophagy and apoptosis in Chinese hamster ovary cell culture. Autophagy 4:70–72
Hwang SO, Lee GM (2008b) Nutrient deprivation induces autophagy as well as apoptosis in Chinese hamster ovary cell culture. Biotechnol Bioeng 99:678–685
Ifandi V, Al-Rubeai M (2005) Regulation of cell proliferation and apoptosis in CHO-K1 cells by the coexpression of c-Myc and Bcl-2. Biotechnol Prog 21:671–677
Ishaque A, Al-Rubeai M (1998) Use of intracellular pH and annexin-V flow cytometric assays to monitor apoptosis and its suppression by bcl-2 over-expression in hybridoma cell culture. J Immunol Methods 221:43–57
Itoh Y, Ueda H, Suzuki E (1995) Overexpression of bcl-2, apoptosis suppressing gene: Prolonged viable culture period of hybridoma and enhanced antibody production. Biotechnol Bioeng 48:118–122
Kabeya Y, Mizushima N, Ueno T et al (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728
Kauffmann-Zeh A, Rodriguez-Viciana P, Ulrich E et al (1997) Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3) K and PKB. Nature 385:544–548
Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: A basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer 26:239–257
Kessel D, Reiners JJ Jr (2007) Initiation of apoptosis and autophagy by the Bcl-2 antagonist HA14–1. Cancer Lett 249:294–299
Kim NS, Lee GM (2001) Overexpression of bcl-2 inhibits sodium butyrate-induced apoptosis in Chinese hamster ovary cells resulting in enhanced humanized antibody production. Biotechnol Bioeng 71:184–193
Kim NS, Lee GM (2002a) Inhibition of sodium butyrate-induced apoptosis in recombinant Chinese hamster ovary cells by constitutively expressing antisense RNA of caspase-3. Biotechnol Bioeng 78:217–228
Kim NS, Lee GM (2002b) Response of recombinant Chinese hamster ovary cells to hyperosmotic pressure: effect of Bcl-2 overexpression. J Biotechnol 95:237–248
Kim YG, Kim JY, Mohan C, et al (2009) Effect of Bcl-xl overexpression on apoptosis and autophagy in Recombinant chinese Hamster overy cells under nutrient-deprived condition. Biotechnol Bioeng
Kovacs AL, Grinde B, Seglen PO (1981) Inhibition of autophagic vacuole formation and protein degradation by amino acids in isolated hepatocytes. Exp Cell Res 133:431–436
Ku B, Woo JS, Liang C et al (2008) Structural and biochemical bases for the inhibition of autophagy and apoptosis by viral BCL-2 of murine gamma-herpesvirus 68. PLoS Pathog 4:e25
Kuo PL, Hsu YL, Cho CY (2006) Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells. Mol Cancer Ther 5:3209–3221
Lai D, Fu L, Weng S et al (2004) Blocking caspase-3 activity with a U6 SnRNA promoter-driven ribozyme enhances survivability of CHO cells cultured in low serum medium and production of interferon-beta. Biotechnol Bioeng 85:20–28
Lee SK, Lee GM (2003) Development of apoptosis-resistant dihydrofolate reductase-deficient Chinese hamster ovary cell line. Biotechnol Bioeng 82:872–876
Levine B (2005) Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 120:159–162
Levine B, Klionsky DJ (2004) Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6:463–477
Levine B, Yuan J (2005) Autophagy in cell death: an innocent convict? J Clin Invest 115:2679–2688
Liang XH, Kleeman LK, Jiang HH et al (1998) Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol 72:8586–8596
Liang XH, Jackson S, Seaman M et al (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402:672–676
Liang C, Feng P, Ku B et al (2006) Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol 8:688–699
Lim SF, Chuan KH, Liu S et al (2006) RNAi suppression of Bax and Bak enhances viability in fed-batch cultures of CHO cells. Metab Eng 8:509–522
Liston P, Roy N, Tamai K et al (1996) Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 379:349–353
Lockshin RA, Williams CM (1964) Programmed cell death. II. Endocrine potentiation of the breakdown of the intersegmental muscles of silkmoths. J Insect Physiol 10:643–649
Lum JJ, DeBerardinis RJ, Thompson CB (2005) Autophagy in metazoans: cell survival in the land of plenty. Nat Rev Mol Cell Biol 6:439–448
Maiuri MC, Criollo A, Tasdemir E et al (2007a) BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between beclin 1 and Bcl-2/Bcl-X(L). Autophagy 3:374–376
Maiuri MC, Le Toumelin G, Criollo A et al (2007b) Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J 26:2527–2539
Mastrangelo AJ, Hardwick JM, Bex F et al (2000a) Part I Bcl-2 and Bcl-x(L) limit apoptosis upon infection with alphavirus vectors. Biotechnol Bioeng 67:544–554
Mastrangelo AJ, Hardwick JM, Zou S et al (2000b) Part II overexpression of bcl-2 family members enhances survival of mammalian cells in response to various culture insults. Biotechnol Bioeng 67:555–564
Meents H, Enenkel B, Eppenberger HM et al (2002) Impact of coexpression and coamplification of sICAM and antiapoptosis determinants bcl-2/bcl-x(L) on productivity, cell survival, and mitochondria number in CHO-DG44 grown in suspension and serum-free media. Biotechnol Bioeng 80:706–716
Meijer AJ, Codogno P (2004) Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol 36:2445–2462
Mercille S, Massie B (1999) Apoptosis-resistant E1B–19 K-expressing NS/0 myeloma cells exhibit increased viability and chimeric antibody productivity under perfusion culture conditions. Biotechnol Bioeng 63:529–543
Miron M, Sonenberg N (2001) Regulation of translation via TOR signaling: insights from Drosophila melanogaster. J Nutr 131:2988S–29893S
Mizushima N (2004) Methods for monitoring autophagy. Int J Biochem Cell Biol 36:2491–2502
Mizushima N, Yamamoto A, Hatano M et al (2001) Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. J Cell Biol 152:657–68
Mizushima N, Yamamoto A, Matsui M et al (2004) In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 15:1101–1111
Moore A, Donahue CJ, Hooley J et al (1995) Apoptosis in CHO cell batch cultures: examination by flow cytometry. Cytotechnology 17:1–11
Morris AE, Schmid J (2000) Effects of insulin and LongR(3) on serum-free Chinese hamster ovary cell cultures expressing two recombinant proteins. Biotechnol Prog 16:693–697
Mortimore GE, Pösö AR (1988) Amino acid control of intracellular protein degradation. Methods Enzymol 166:461–476
Munzert E, Muthing J, Buntemeyer H et al (1996) Sialidase activity in culture fluid of Chinese hamster ovary cells during batch culture and its effect on recombinant human antithrombin III integrity. Biotechnol Prog 12:559–563
Nivitchanyong T, Martinez A, Ishaque A et al (2007) Anti-apoptotic genes Aven and E1B–19 K enhance performance of BHK cells engineered to express recombinant factor VIII in batch and low perfusion cell culture. Biotechnol Bioeng 98:825–841
Oberstein A, Jeffrey PD, Shi Y (2007) Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein. J Biol Chem 282:13123–13132
Oh HK, So MK, Yang J et al (2005) Effect of N-acetylcystein on butyrate-treated Chinese hamster ovary cells to improve the production of recombinant human interferon-beta-1a. Biotechnol Prog 21:1154–1164
Oldham S, Hafen E (2003) Insulin/IGF and target of rapamycin signaling: A TOR de force in growth control. Trends Cell Biol 13:79–85
Pattingre S, Tassa A, Qu X et al (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927–939
Petiot A, Ogier-Denis E, Blommaart EF et al (2000) Distinct classes of phosphatidylinositol 3′-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J Biol Chem 275:992–998
Raught B, Gingras AC, Sonenberg N (2001) The target of rapamycin (TOR) proteins. Proc Natl Acad Sci USA 98:7037–7044
Reed JC (1994) Bcl-2 and the regulation of programmed cell death. J Cell Biol 124:1–6
Saeki K, Yuo A, Okuma E et al (2000) Bcl-2 down-regulation causes autophagy in a caspase-independent manner in human leukemic HL60 cells. Cell Death Differ 7:1263–1269
Salvesen GS, Riedl SJ (2008) Caspase mechanisms. Adv Exp Med Biol 615:13–23
Sauerwald TM, Betenbaugh MJ, Oyler GA (2002) Inhibiting apoptosis in mammalian cell culture using the caspase inhibitor XIAP and deletion mutants. Biotechnol Bioeng 77:704–716
Sauerwald TM, Oyler GA, Betenbaugh MJ (2003) Study of caspase inhibitors for limiting death in mammalian cell culture. Biotechnol Bioeng 81:329–340
Sauerwald TM, Figueroa B Jr, Hardwick JM et al (2006) Combining caspase and mitochondrial dysfunction inhibitors of apoptosis to limit cell death in mammalian cell cultures. Biotechnol Bioeng 94:362–372
Schmelzle T, Hall MN (2000) TOR, a central controller of cell growth. Cell 103:253–262
Schworer CM, Mortimore GE (1979) Glucagon-induced autophagy and proteolysis in rat liver: Mediation by selective deprivation of intracellular amino acids. Proc Natl Acad Sci USA 76:3169–3173
Scorrano L, Korsmeyer SJ (2003) Mechanisms of cytochrome c release by proapoptotic bcl-2 family members. Biochem Biophys Res Commun 304:437–444
Scott PH, Brunn GJ, Kohn AD et al (1998) Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway. Proc Natl Acad Sci USA 95:7772–7777
Seglen PO, Gordon PB (1982) 3-Methyladenine: Specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci USA 79:1889–1892
Shimizu S, Kanaseki T, Mizushima N et al (2004) Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol 6:1221–1228
Siegel RM, Lenardo MJ (2002) Apoptosis signaling pathways. Curr Protoc Immunol. Chapter 11: 44:Unit 11.9C
Simpson NH, Milner AE, Al-Rubeai M (1997) Prevention of hybridoma cell death by bcl-2 during suboptimal culture conditions. Biotechnol Bioeng 54:1–16
Singh R, Al-Rubeai M, Gregory C et al (1994) Cell death in bioreactors-a role for apoptosis. Biotechnol Bioeng 4:720–726
Singh RP, Finka G, Emery AN et al (1997) Apoptosis and its control in cell culture systems. Cytotechnology 3:87–93
Subramanian T, Chinnadurai G (2003) Pro-apoptotic activity of transiently expressed bcl-2 occurs independent of BAX and BAK. J Cell Biochem 89:1102–1114
Sung YH, Lee GM (2005) Enhanced human thrombopoietin production by sodium butyrate addition to serum-free suspension culture of bcl-2-overexpressing CHO cells. Biotechnol Prog 21:50–57
Sung YH, Hwang SJ, Lee GM (2005) Influence of down-regulation of caspase-3 by siRNAs on sodium-butyrate-induced apoptotic cell death of Chinese hamster ovary cells producing thrombopoietin. Metab Eng 7:457–466
Sung YH, Lee JS, Park SH et al (2007) Influence of co-down-regulation of caspase-3 and caspase-7 by siRNAs on sodium butyrate-induced apoptotic cell death of Chinese hamster ovary cells producing thrombopoietin. Metab Eng 5–6:452–464
Takeuchi H, Kondo Y, Fujiwara K et al (2005) Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors. Cancer Res 65:3336–3346
Teige M, Weidemann R, Kretzmer G (1994) Problems with serum-free production of antithrombin III regarding proteolytic activity and product quality. J Biotechnol 34:101–105
Terada S, Fukuoka K, Fujita T et al (1997) Anti-apoptotic genes, bag-1 and bcl-2, enabled hybridoma cells to survive under treatment for arresting cell cycle. Cytotechnology 25:17–23
Tey BT, Singh RP, Piredda L et al (2000a) Bcl-2 mediated suppression of apoptosis in myeloma NS0 cultures. J Biotechnol 79:147–159
Tey BT, Singh RP, Piredda L et al (2000b) Influence of bcl-2 on cell death during the cultivation of a Chinese hamster ovary cell line expressing a chimeric antibody. Biotechnol Bioeng 8:31–43
Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316
Tokunaga C, Yoshino K, Yonezawa K (2004) mTOR integrates amino acid- and energy-sensing pathways. Biochem Biophys Res Commun 313:443–446
Trump BF, Berezesky IK, Osornio-Vargas AR (1981) Cell death and the disease process. The role of calcium. In: Bowen ID, Lockshin RA (eds) Cell death in biology and pathology. Chapman and Hall, New York
Tsukada M, Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333:169–174
Vaux DL, Haecker G, Strasser A (1994) An evolutionary perspective on apoptosis. Cell 76:777–779
Wong DC, Wong KT, Nissom PM et al (2006) Targeting early apoptotic genes in batch and fed-batch CHO cell cultures. Biotechnol Bioeng 95:350–361
Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306
Yorimitsu T, Klionsky DJ (2005) Autophagy: Molecular machinery for self-eating. Cell Death Differ 12:1542–1552
Yu L, Alva A, Su H et al (2004) Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304:1500–1502
Yun CY, Liu S, Lim SF et al (2007) Specific inhibition of caspase-8 and -9 in CHO cells enhances cell viability in batch and fed-batch cultures. Metab Eng 9:406–418
Zanghi JA, Fussenegger M, Bailey JE (1999) Serum protects protein-free competent Chinese hamster ovary cells against apoptosis induced by nutrient deprivation in batch culture. Biotechnol Bioeng 64:108–119
Zanghi JA, Renner WA, Bailey JE et al (2000) The growth factor inhibitor suramin reduces apoptosis and cell aggregation in protein-free CHO cell batch cultures. Biotechnol Prog 16:319–325
Zhang Z, Vuori K, Reed JC et al (1995) The alpha 5 beta 1 integrin supports survival of cells on fibronectin and up-regulates Bcl-2 expression. Proc Natl Acad Sci USA 92:6161–6165
Zhou W, Chen CC, Buckland B et al (1997) Fed-batch culture of recombinant NS0 myeloma cells with high monoclonal antibody production. Biotechnol Bioeng 55:783–792
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Mohan, C., Kim, YG., Lee, G.M. (2009). Apoptosis and Autophagy Cell Engineering. In: Al-Rubeai, M. (eds) Cell Line Development. Cell Engineering, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2245-5_10
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