Engineering challenges in high density cell culture systems.

Abstract:

:High density cell culture systems offer the advantage of production of bio-pharmaceuticals in compact bioreactors with high volumetric production rates; however, these systems are difficult to design and operate. First of all, the cells have to be retained in the bioreactor by physical means during perfusion. The design of the cell retention is the key to performance of high density cell culture systems. Oxygenation and media design are also important for maximizing the cell number. In high density perfusion reactors, variable cell density, and hence the metabolic demand, require constant adjustment of perfusion rates. The use of cell specific perfusion rate (CSPR) control provides a constant environment to the cells resulting in consistent production. On-line measurement of cell density and metabolic activities can be used for the estimation of cell densities and the control of CSPR. Issues related to mass transfer and mixing become more important at high cell densities. Due to the difference in mass transfer coefficients for oxygen and CO(2), a significant accumulation of dissolved CO(2) is experienced with silicone tubing aeration. Also, mixing is observed to decrease at high densities. Base addition, if not properly done, could result in localized cell lysis and poor culture performance. Non-uniform mixing in reactors promotes the heterogeneity of the culture. Cell aggregation results in segregation of the cells within different mixing zones. This paper discusses these issues and makes recommendations for further development of high density cell culture bioreactors.

journal_name

Cytotechnology

journal_title

Cytotechnology

authors

Ozturk SS

doi

10.1007/BF00353919

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

3-16

issue

1-3

eissn

0920-9069

issn

1573-0778

journal_volume

22

pub_type

杂志文章
  • Formation of multilayer rosettes in phytohemagglutinin-stimulated lymphocytes: correlation with chromatin condensation conformation in premature chromosome condensation.

    abstract::We found that the formation of multilayer rosettes by transformed human blood lymphocytes after phytohemagglutinin (PHA) stimulation is correlated with conformational changes of the chromatin as seen by premature chromosome condensation (PCC). The frequency distribution of grades of PCC and multilayer rosette formatio...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/BF00145027

    authors: Thomou H,Sambani C,Kitsiou P,Politis G

    更新日期:1988-07-01 00:00:00

  • Epithelial properties of human intestinal Caco-2 cells cultured in a serum-free medium.

    abstract::Human intestinal Caco-2 cells were cultured under serum-free conditions on an insoluble collagen and FCS matrix (Caco-2-SF), and a comparison was made between several characteristics of Caco-2 and Caco-2-SF cells. Their morphological appearance was identical. Slight differences were found in cell growth and expression...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/BF00749813

    authors: Hashimoto K,Shimizu M

    更新日期:1993-01-01 00:00:00

  • Chaperone and foldase coexpression in the baculovirus-insect cell expression system.

    abstract:CONCLUSIONS:The BEVS has become widely utilized for production of recombinant proteins. However, protein aggregation and inefficient processing often limit yields, especially for secreted and membrane proteins. Since many proteins of pharmaceutical interest require similar posttranslational processing steps, engineerin...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/BF00350396

    authors: Betenbaugh MJ,Ailor E,Whiteley E,Hinderliter P,Hsu TA

    更新日期:1996-01-01 00:00:00

  • A regulatable selective system facilitates isolation of heterologous protein hyper-producing mammalian cells without gene amplification.

    abstract::In this article, we describe a new method that facilitates to isolate mammalian cells inducible hyper-producing heterologous proteins. This method uses the tetracycline-inducible system to express both the selection marker and the heterologous gene, therefore, allows to increase the selection pressure by reducing the ...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1023/A:1023945517446

    authors: Teruya K,Zhang Y,Katakura Y,Shirahata S

    更新日期:2002-11-01 00:00:00

  • Endogenous synthesis of prostacyclin was positively regulated during the maturation phase of cultured adipocytes.

    abstract::Prostacyclin alternatively called prostaglandin (PG) I2 is an unstable metabolite synthesized by the arachidonate cyclooxygenase pathway. Earlier studies have suggested that prostacyclin analogues can act as a potent effector of adipose differentiation. However, biosynthesis of PGI2 has not been determined comprehensi...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-013-9616-9

    authors: Rahman MS,Khan F,Syeda PK,Nishimura K,Jisaka M,Nagaya T,Shono F,Yokota K

    更新日期:2014-08-01 00:00:00

  • Mechanisms of resistance to alkylating agents.

    abstract::Alkylating agents are the most widely used anticancer drugs whose main target is the DNA, although how exactly the DNA lesions cause cell death is still not clear. The emergence of resistance to this class of drugs as well as to other antitumor agents is one of the major causes of failure of cancer treatment. This pap...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1023/A:1008060720608

    authors: Damia G,D'Incalci M

    更新日期:1998-09-01 00:00:00

  • Regulation and expression of transforming growth factor type-beta during early mammalian development.

    abstract::We have examined the effect of differentiation on the expression of different members of the transforming growth factor type-beta (TGF-beta) family using embryonal carcinoma (EC) cells and early mammalian embryos. We determined that TGF-beta activity increases approximately 25-100% when the mouse EC cell line, F9, is ...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/BF00563783

    authors: Kelly D,Campbell WJ,Tiesman J,Rizzino A

    更新日期:1990-11-01 00:00:00

  • Effects of cell density and phorbol esters on the expression of epidermal growth factor receptors.

    abstract::Previously, it has been shown that the binding of epidermal growth factor (EGF) by a wide range of cells decreases as cell density increases. In this report, we demonstrate that KB cells treated chronically with phorbol esters continue to exhibit decreases in EGF receptor binding as cell density increases. This findin...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/BF00350914

    authors: Rizzino A,Huebert C,Kuszynski C,Wilder PJ

    更新日期:1991-10-01 00:00:00

  • Lithium chloride promotes neuronal differentiation of rat neural stem cells and enhances neural regeneration in Parkinson's disease model.

    abstract::Parkinson's disease (PD) is one of the most common neural degenerative disease, affecting millions of people globally. Great progress has been made in the PD treatment, and one of the most promising one is the stem cell-based therapy. Thus, studies on the differentiation of neural stem cells (NSCs) are important to th...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-016-0056-1

    authors: Qi L,Tang Y,He W,Pan H,Jiang W,Wang L,Deng W

    更新日期:2017-04-01 00:00:00

  • The transient expression of CHIKV VLP in large stirred tank bioreactors.

    abstract::Transient gene expression (TGE) bioprocesses have been difficult to scale up in large stirred tank bioreactors with volumes of more than 1.5 L. Low production levels are often observed, but the causes have not been investigated (Gutierrez-Granados et al. in Crit Rev Biotechnol 38:918-940, 2018). Chikungunya Virus-like...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-019-00346-x

    authors: Chen P,Demirji J,Ivleva VB,Horwitz J,Schwartz R,Arnold F

    更新日期:2019-12-01 00:00:00

  • Culture phases, cytotoxicity and protein expressions of agarose hydrogel induced Sp2/0, A549, MCF-7 cell line 3D cultures.

    abstract::Advancements in cell cultures are occurring at a rapid pace, an important direction is culturing cells in 3D conditions. We demonstrate the usefulness of agarose hydrogels in obtaining 3 dimensional aggregates of three cell lines, A549, MCF-7 and Sp2/0. The differences in culture phases, susceptibility to cisplatin-in...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-014-9795-z

    authors: Ravi M,Kaviya SR,Paramesh V

    更新日期:2016-05-01 00:00:00

  • Small interfering RNA knockdown of mini-TyrRS and mini-TrpRS effects angiogenesis in human umbilical vein endothelial cells in hypoxic culture.

    abstract::Aim We studied the role of mini-TyrRS and mini-TrpRS in angiogenesis by using small interfering RNA-mediated mini-TyrRS/mini-TrpRS knockout in hypoxic culture of human umbilical vein endothelial cells. Methods SiRNA was used as the main method to inhibited the gene function. Silencing efficiency was assayed by real-ti...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-008-9151-2

    authors: Zeng R,Chen YC,Zeng Z,Liu R,Qiang O,Jiang XF,Liu XX,Li X,Wang HY

    更新日期:2008-03-01 00:00:00

  • Sufentanil protects the rat myocardium against ischemia-reperfusion injury via activation of the ERK1/2 pathway.

    abstract::Sufentanil, a lipophilic opioid, is the most frequently used clinical drug for ischemic heart disease. The effects of sufentanil on MAPK signaling in ischemic heart disease were explored. The effects of sufentanil on ischemia-reperfusion (IR)-induced myocardial injury in a rat model were examined. The serum levels of ...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-017-0127-y

    authors: Tao H,Nuo M,Min S

    更新日期:2018-02-01 00:00:00

  • Septin 6 localizes to microtubules in neuronal dendrites.

    abstract::In neuronal dendrites, septins localize to the base of the spine, a unique position which is sandwiched between the microtubule (MT)-rich dendritic shaft and the actin filament-rich spine. Here, we provide evidence for the association of SEPT6 with MTs in cultured rat hippocampal neurons. In normal cultures, SEPT6 clu...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-012-9477-7

    authors: Moon IS,Lee H,Walikonis RS

    更新日期:2013-03-01 00:00:00

  • Intracellular localisation studies of doxorubicin and Victoria Blue BO in EMT6-S and EMT6-R cells using confocal microscopy.

    abstract::The subcellular localisation of doxorubicin and Victoria Blue BO (VBBO) in a murine mammary tumour cell line EMT6-S, and the resistant sub-lineEMT6-R was studied, using confocal microscopy, in order to investigate their sites of action. In cells treated with doxorubicin (10 mu M) for 90 min, the pattern of intracellul...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1023/A:1022435829894

    authors: Burrow SM,Phoenix DA,Wainwright M,Tobin MJ

    更新日期:2002-05-01 00:00:00

  • On-line heat flux measurements improve the culture medium for the growth and productivity of genetically engineered CHO cells.

    abstract::With the increasingly competitive commercial production of target proteins by hybridoma and genetically engineered cells, there is an urgent requirement for biosensors to monitor and control on-line and in real time the growth of cultured cells. Since growth is accompanied by an enthalpy change, heat dissipation measu...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1023/A:1008038515285

    authors: Guan YH,Kemp RB

    更新日期:1999-07-01 00:00:00

  • A rat mammary gland cancer cell with stem cell properties of self-renewal and multi-lineage differentiation.

    abstract::The cancer stem cell hypothesis posits that tumors are derived from a single cancer-initiating cell with stem cell properties. The task of identifying and characterizing cancer-initiating cells with stem cell properties at the single cell level has proven technically difficult because of the scarcity of the cancer ste...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-008-9173-9

    authors: Cocola C,Sanzone S,Astigiano S,Pelucchi P,Piscitelli E,Vilardo L,Barbieri O,Bertoli G,Reinbold RA,Zucchi I

    更新日期:2008-09-01 00:00:00

  • The insulin-like growth factor II/mannose-6-phosphate receptor : IGF-II/Man-6-P receptor.

    abstract::Recent evidence from molecular cloning, biochemical and immunological experiments has established that the cation-independent mannose-6-phosphate (Man-6-P) receptor and insulin-like growth factor-II (IGF-II) receptor are the same protein. Although the role of the IGF-II/Man-6-P receptor as a transporter of hydrolytic ...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/BF00364994

    authors: Macdonald RG

    更新日期:1989-12-01 00:00:00

  • Analysis of toxicity effects of Di-(2-ethylhexyl) phthalate exposure on human bronchial epithelial 16HBE cells.

    abstract::Recent studies have indicated that Di-(2-ethylhexyl) phthalate (DEHP), the most commonly used plasticizer in daily-life products, could be dispersed in indoor air and induce human exposure via inhalation. DEHP has been reported to have effects on the respiratory system in both animal and human researches. The toxicity...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-017-0111-6

    authors: Ma Y,Guo Y,Wu S,Lv Z,Zhang Q,Xie X,Ke Y

    更新日期:2018-02-01 00:00:00

  • Production of immunoglobulin A in different reactor configurations.

    abstract::A murine hybridoma line (Zac3), secreting an IgA monoclonal antibody, was cultivated in different systems: a BALB/c mouse, a T-flask, a stirred-tank bioreactor and a hollow fiber reactor. These systems were characterized in terms of cell metabolism and performances for IgA production. Cultures in T-flask and batch bio...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/BF00749221

    authors: Stoll T,Perregaux C,von Stockar U,Marison IW

    更新日期:1995-02-01 00:00:00

  • Evaluation of electroporation-induced adverse effects on adipose-derived stem cell exosomes.

    abstract::In the recent years, the possibility of utilizing extracellular vesicles for drug delivery purposes has been investigated in various models, suggesting that these vesicles may have such potential. In addition to the choice of donor cell type for vesicle production, a major obstacle still exists with respect of loading...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-016-9952-7

    authors: Johnsen KB,Gudbergsson JM,Skov MN,Christiansen G,Gurevich L,Moos T,Duroux M

    更新日期:2016-10-01 00:00:00

  • DNA and cell death.

    abstract::The type of DNA damage and the role of poly (ADP-ribosyl) polymerase (ADPRP) and sulphated glyprotein 2 (SGP-2) in programmed cell death (apoptosis) was investigated in the following model systems: i) rat thymocytes treated with dexamethasone (DEX) eitherin vitro orin vivo; ii) human perypheral blood mononuclear cells...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/BF00736814

    authors: Monti D,Troiano L,Tropea F,Grassilli E,Cossarizza A,Barozzi D,Bettuzzi S,Corti A,Franceschi C

    更新日期:1991-02-01 00:00:00

  • Identification of the pivotal role of glutamate in enhancing insect cell growth using factor analysis.

    abstract::Although the insect cell/baculovirus system is an important expression platform for recombinant protein production, our understanding of insect cell metabolism with respect to enhancing cell growth capability and productivity is still limited. Moreover, different host insect cell lines may have different growth charac...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-013-9637-4

    authors: Chou CC

    更新日期:2014-10-01 00:00:00

  • Visible light regulates neurite outgrowth of nerve cells.

    abstract::The neurite outgrowth of PC12 cells on collagen-coated glass plates under light emitting diode (LED) irradiation at several wavelengths (i.e., 455, 470, 525, 600, 630, 880 and 945 nm) was investigated. No neurite outgrowth was observed during cultivation under irradiation from the lamp of an inverted light microscope ...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-007-9087-y

    authors: Higuchi A,Watanabe T,Noguchi Y,Chang Y,Chen WY,Matsuoka Y

    更新日期:2007-07-01 00:00:00

  • Rapid detection of cytotoxicity of food additives and contaminants by a novel cytotoxicity test, menadione-catalyzed H(2)O (2) production assay.

    abstract::Menadione-catalyzed H(2)O(2) production by viable animal cells was proportional to the viable cell number, and H(2)O(2) production decreased with increasing cytotoxic effects after the incubation of cells with cytotoxic compounds. The cytotoxic effects of food additives, pesticides, antibiotics, heavy metals, phytotox...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1023/A:1020580818979

    authors: Yamashoji S,Isshiki K

    更新日期:2001-11-01 00:00:00

  • Accuracy of the endpoint assay for virus titration.

    abstract::The statistics of estimators used with the endpoint assay for virus titration were investigated. For a standard assay with 10 wells/dilution, the graphical estimator traditionally used was found to produce estimates with significant positive bias and a relatively low accuracy. Furthermore, the graphical estimator was ...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/BF02522040

    authors: Nielsen LK,Smyth GK,Greenfield PF

    更新日期:1992-01-01 00:00:00

  • A simple method for in situ freezing of anchorage-dependent cells including rat liver parenchymal cells.

    abstract::We developed a simple method for freezing anchorage-dependent cells, including primary cultured rat liver parenchymal cells, without detaching the cells from the culture dish. The method consists of preculture of the cells to confluence, changing the growth medium to a conventional freezing medium, packaging in a cont...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/BF00556297

    authors: Ohno T,Saijo-Kurita K,Miyamoto-Eimori N,Kurose T,Aoki Y,Yosimura S

    更新日期:1991-03-01 00:00:00

  • Improvement in the antibody productivity of human-human hybridomas by transfection with Tac gene.

    abstract::The presence of a highly purified recombinant interleukin-2 (rIL-2) increased the production of immunoglobulin (IgM or IgG) by human-human hybridomas to 1.5-2.0 times the production by untreated cells. However, these cells did not react with anti-Tac (IL-2 receptor alpha) antibody. To enhance the response of the hybri...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/BF00148808

    authors: Iwamoto K,Shintani Y,Sasada R,Honjo T,Kitano K

    更新日期:1990-07-01 00:00:00

  • Cytoglobin: a potential marker for adipogenic differentiation in preadipocytes in vitro.

    abstract::Obesity, mainly characterized by the excess fat storage, is a global health problem resulting in serious morbidity and mortality. Identification of molecular mechanisms in adipogenic differentiation pathway might lead to development of new strategies for diagnosis, prevention and therapy of obesity and associated dise...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-016-0047-2

    authors: Doğan A,Demirci S,Kıratlı B,Şahin F

    更新日期:2017-02-01 00:00:00

  • Modified method for effective primary vascular smooth muscle progenitor cell culture from peripheral blood.

    abstract::In previous studies, vascular smooth muscle progenitor cells (vSMPCs) isolated from peripheral blood mononuclear cells (PBMCs) were cultured using medium containing platelet-derived growth factor-BB (PDGF-BB) for 4 weeks. However, this method requires long culture periods of up to 4 weeks and yields low cell counts. T...

    journal_title:Cytotechnology

    pub_type: 杂志文章

    doi:10.1007/s10616-020-00419-2

    authors: Seong JH,Song YS,Joo HW,Park IH,Shen GY,Shin NK,Lee AH,Kwon AM,Lee Y,Kim H,Kim KS

    更新日期:2020-10-01 00:00:00