Status and developments of animal cell technology using suspension culture techniques

Abstract

I n this review the state of the art in animal cell technology, using suspension culture techniques is updated as far as the end of 1980. We have tried to discuss, on a broad basis, the current status and potential developements of both, the purely biological and the biochemical engineering aspects which may be important to improve the performance and design of animal cell technologies. The process economics could be considerably improved by the use of transformed animal cell substrates, the use of cheaper cultivation media and by methodological and engineering means. Most of these aspects are in the state of rcalization. Nevertheless, for a great variety of biological active sub-. stances which do not require coor posttranslntional processing, recombinant DNA-techniques (e.g. genetic engineering) are a promising alternative for the production of animal cell derived substances. Zusammenfassung Mit diesem Beitrag wird versucht, eine Obersicht uber den Entwicklungsstand der ,,Technologic mit tierischen Zellen" (begrenzt auf Verfahren mit Suspensionskulturen) mit Status Ende 1980 zu vermitteln. Wir haben dabei versucht, zur Zeit schon ctablierte Verfahren wie auch potentielle Entwicklungsmoglichkeiten dieser Technologie aufzuzeigen und zu diskutieren. Es wurden hierbei sowohl die rein biologischen Aspekte somie die sich daraus ergebenden Konsequenzen fiir die biologische Verfahrenstechnik im Rinblick auf die Verfahrensabwicklung und Moglichkeiten der ProzeBverbessemg analysiert. Die Technologie mit tierischen Zellen kann durch den vermehrten Einsatz transformierter Zellen als Produktionsvehikel, die Entwicklung billiger Niihrmedien und die Verbesserung der Massenkultivierung auf methodischer wie verfahrenstechnischer Ebeno noch wesentlich verbessert werden. Viele der genannten Verbesserungsmoglichkeiten sind im Entwicklungsstadium. Fiir die Produktion einer Reihe von bioaktiven Wirkstoffen am tierischen Zellen, welche fur ihre Biospthese cooder posttranslationale Modifikationen nicht erfordern, sehen wir die bessere Alternative in der DNA-Technologie (z. B. mittels der Gentechnik). PrefaceThis review article is the full text of an invited lecture held a t the "Chemap Cell Culture Symposium", sponsored and organized by the Chemap AG in January 1980. The state of the art in animal cell technology, using suspension culture techniques has been updated as far as the end of 1980. It is mainly addressed to biotechnologists who are ,,non-specialists" in the field of animal cell technology.

Model of oxygen transport limitations in hollow fiber bioreactors

“…The specific oxygen uptake rate for growing CRL-1606 was 0.1 pmol/ cell h31 and is typical for mammalian cell^.^',^^ However, it may be that resting cells in immobilized reactors have a lower oxygen uptake rate. 34 The kinetics were estimated to be zero order since the K, for oxygen uptake of mammalian cells is less than 1 pM.35, 36 Such an assumption greatly simplifies the mathematical analysis. This is probably a valid approximation particularly since many of the other parameters used in immobilized cell reactor mass transport analysis are uncertain.…”

“…and (32a) are appropriate for the integration of the shell-side equation (16) when oxygen is radially limiting: [shell-side ( R I r I yR)] (33) Boundary conditions (31) and (32b) are appropriate when oxygen is not limiting in the shell-side: C = C ( R ) ---1 --+ -l n -""'(: Dt? ( (8)') : (8))[shell-side ( R I r I pR)](34) …”

Effect of Spatial Segregation on Commensalistic Cultures—Series Reactors

“…Even in controlled settings in research laboratories and industrial complexes, these variations are common. , Environmental partitioning in (bio)reactors arises when multiple reactors are used in series-parallel configuration or when multichamber reactors are used. Use of bioreactors (cell cultures) in series, considered here, is the norm for and an integral part of cultivation of living cells at bench, laboratory, pilot, and commercial scales. − …”

Insect Cell Culture: Fundamental and Applied Aspects

“…In contrast to the impeller-stirred vessels, bubblecolumn and air-lift type of bioreactors have been used relatively scarcely as devices to determine and quantify the fragility of cells, even though they are of great interest for use as bioreactors for growth of fragile cells (Katinger & Scheirer, 1982). In fact, only three or four groups have studied and used bubble columns and air lifts in this respect.…”