The Use of Peptones as Medium Additives for High-Density Perfusion Cultures of Animal Cells

Heidemann, Rüdiger; Zhang, C.; Qi, Hans; Rule, J.; Rozales, Carl; Park, S.; Chuppa, Sandra; Ray, Manas K.; Michaels, James; Konstantinov, Konstantin; Naveh, D.

doi:10.1007/0-306-46875-1_45

Cited by 41 publications

(65 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Nevertheless, the risk of contamination by viruses, mycoplasma or prions from animal supplement led to a strong demand for media formulations free from animal components (Grillberger et al 2009). Then, the search for culture media that most closely replicated the benefits of animal-derived sera without their biosafety risks provoked a growing interest in the use of plant peptones (Heidemann et al 2000;Burteau et al 2003;Farges et al 2008) or yeast extracts (YE) (Sung et al 2004;Kim and Lee 2009).…”

Section: Introductionmentioning

confidence: 99%

“…On one hand, some results suggested the presence of growth factor-like and anti-apoptotic peptides from plant peptones (Burteau et al 2003;Farges et al 2008;Franek and Katinger 2002) or YE (Sung et al 2004), but without experimental validations. On the other hand, other studies concluded on nutritional efficiency of plant peptones as amino acid sources (Heidemann et al 2000;Nyberg et al 1999). Nevertheless, the addition of nutritional as well as ''bioactive'' compounds may improve the efficiency of energetic cell metabolism.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Combination of yeast hydrolysates to improve CHO cell growth and IgG production

et al. 2012

View full text Add to dashboard Cite

Many studies underlined the great benefits of hydrolysates used as additives in animal free media on cell culture performances. However, to precisely define hydrolysate supplementation strategies, a deeper understanding of their effect on cell growth and protein production is required. In the present study, the effect of addition of one yeast extract (YE) and two yeast peptones (named YP.A and YP.B) in a chemically defined medium was first assessed on cell culture performances. Interestingly, specific effects were found depending on the degree of degradation of yeast hydrolysates. The YE at 1 g L -1 increased the maximal cell density by 70 %, while a mixture of YE (1 g L -1 ) and YP.A (4 g L -1 ) increased IgG production by 180 %. These conditions were then evaluated on the CHO cell kinetics all over cultures. Hydrolysates extended the cell growth phase in Erlenmeyer flask and increased the maximal growth rate in bioreactor up to 20 %. Cell growth stimulation induced by hydrolysates addition was linked with energetic metabolism improvement suggesting that they promote oxidative pathway. Furthermore, hydrolysates provided an additional source of substrate that supported cell growth despite glutamine limitation.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combination of yeast hydrolysates to improve CHO cell growth and IgG production

et al. 2012

View full text Add to dashboard Cite

show abstract

“…First, proteolytic cleavages of plant protein hydrolysates generating smaller peptides and amino acids could occur either at the cell surface or in the extracellular medium. If they were internalised through specific transporters (Heidemann et al 2000;Burteau et al 2003), once viability dropped, they could accumulate in the extracellular medium. This assumes that the hydrolysis of peptones is slower than the transport of the resulting amino acids, di-or tripeptides inside the cells.…”

Section: Effects Of Wheat Protein (Wp) Hydrolysates On Bioreactor Culmentioning

confidence: 99%

“…This could not be explained as a result of mortality, which strongly suggests that, as previously mentioned (Burteau et al 2003), plant protein hydrolysates could improve biosynthesis either on a nutritional basis or/and due to bioactive peptides acting as cell signal inducers (Rassmussen et al 1998). Some authors have suggested that most of the effects shown by some protein hydrolysates may be of a strictly nutritional nature (Heidemann et al 2000). In this hypothesis, peptones are a cheap source of amino acids, possibly with a better uptake potential through peptide transporters.…”

Section: Effects Of Wheat Protein (Wp) Hydrolysates On Bioreactor Culmentioning

confidence: 99%

“…However, the development of such chemically defined protein-free media requires complex, cell line-specific studies and their optimisation sometimes turns out to be very expensive. Nevertheless, since CHO cells can be adapted to serum-free or to protein-free media, according to some authors, the switch to serum-free media can be easier while using protein hydrolysates (or peptones) as supplements (Jan et al 1994;Keen and Rapson 1995;Heidemann et al 2000). Plant peptones, in particular, can be used as a cheap partial substitute to serum to respond to biosafety concerns.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Plant protein hydrolysates support CHO-320 cells proliferation and recombinant IFN-γ production in suspension and inside microcarriers in protein-free media

et al. 2004

View full text Add to dashboard Cite

We have recently developed a protein-free medium (PFS) able to support the growth of Chinese hamster ovary (CHO) cells in suspension. Upon further supplementation with some plant protein hydrolysates, medium performances reached what could be observed in serum-containing media [Burteau et al. In Vitro Cell. Dev. Biol.-Anim. 39 (2003) 291]. Now, we describe the use of rice and wheat protein hydrolysates, as non-nutritional additives to the culture medium to support productivity and cell growth in suspension or in microcarriers. When CHO-320 cells secreting recombinant interferon-gamma (IFN-c) were cultivated in suspension in a bioreactor with our PFS supplemented with wheat hydrolysates, the maximum cell density increased by 25% and the IFN-c secretion by 60% compared to the control PFS. A small-scale perfusion system consisting of CHO-320 cells growing on and inside fibrous microcarriers under discontinuous operation was first developed. Under these conditions, rice protein hydrolysates stimulated recombinant IFN-c secretion by 30% compared to the control PFS. At the bioreactorscale, similar results were obtained but when compared to shake-flasks studies, nutrients, oxygen or toxic by-products gradients inside the microcarriers seemed to be the main limitation of the system. An increase of the perfusion rate to maintain glucose concentration over 5.5 mM and dissolved oxygen (DO) at 60% was able to stimulate the production of IFN-c to a level of 6.6 lg h À1 g À1 of microcarriers after 160 h when a cellular density of about 4 · 10 8 cell g À1 of carriers was reached.Abbreviations: AU -arbitrary units; CHO -Chinese hamster ovary; DO -dissolved oxygen; LDH -lactate deshydrogenase; IFN-c -interferon-gamma; PFA -protein-free medium for adhesion; PFS -protein-free medium for suspension; RP -rice protein hydrolysates; WP -wheat protein hydrolysates.

show abstract

Potential of cell retention techniques for large‐scale high‐density perfusion culture of suspended mammalian cells

Voisard

Meuwly

Ruffieux

et al. 2003

Biotech & Bioengineering

244

150

View full text Add to dashboard Cite

This review focuses on cultivation of mammalian cells in a suspended perfusion mode. The major technological limitation in the scaling-up of these systems is the need for robust retention devices to enable perfusion of medium as needed. For this, cell retention techniques available to date are presented, namely, cross-flow filters, hollow fibers, controlled-shear filters, vortex-flow filters, spin-filters, gravity settlers, centrifuges, acoustic settlers, and hydrocyclones. These retention techniques are compared and evaluated for their respective advantages and potential for large-scale utilization in the context of industrial manufacturing processes. This analysis shows certain techniques have a limited range of perfusion rate where they can be implemented (most microfiltration techniques). On the other hand, techniques were identified that have shown high perfusion capacity (centrifuges and spin-filters), or have a good potential for scale-up (acoustic settlers and inclined settlers). The literature clearly shows that reasonable solutions exist to develop large-scale perfusion processes.

show abstract

The Use of Peptones as Medium Additives for High-Density Perfusion Cultures of Animal Cells

Cited by 41 publications

References 8 publications

Combination of yeast hydrolysates to improve CHO cell growth and IgG production

Combination of yeast hydrolysates to improve CHO cell growth and IgG production

Plant protein hydrolysates support CHO-320 cells proliferation and recombinant IFN-γ production in suspension and inside microcarriers in protein-free media

Potential of cell retention techniques for large‐scale high‐density perfusion culture of suspended mammalian cells

Contact Info

Product

Resources

About