Hydrodymanic Damage To Animal Cells

Critical Reviews in Biotechnology, 21(2):67–110 (2001)

Hydrodynamic Damage to Animal Cells
Yusuf Chisti
Institute of Technology and Engineering, Massey University, Private Bag 11 222, Palmerston North, New Zealand. Telephone: +64-6-356-9099 ext. 2911. Fax: +64-6-350-5604. E-mail address: Y.Chisti@massey.ac.nz

Table of Contents
I. II.Introduction............................................................................................. 68 Shear Forces in Process Equipment ................................................... 68 A. B. C. D. E. F. Gas-Agitated Bioreactors .................................................................. 69 Mechanically Stirred Vessels ............................................................ 73 Pipework and Flow Channels........................................................... 74 Turbulent Jets ................................................................................... 79 Shear Phenomena in Isotropic Turbulence ...................................... 81 Effects of Suspended Particles on Turbulence ................................ 84

III. Shear Effects on Cells........................................................................... 84 A. Suspended Cells ............................................................................... 84 1. 2. B. Hybridomas and Suspension-Adapted Cells ............................. 84 Blood Cells ................................................................................. 91

Adherent Cells .................................................................................. 941. 2. Cells on Stationary Surfaces ..................................................... 94 Cells on Suspended Microcarriers ............................................. 95

C.

Shear Effects on the Cell Cycle ..................................................... 102

IV. Concluding Remarks .......................................................................... 102
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V. Nomenclature ....................................................................................... 104 References ......................................................................................................... 105
ABSTRACT: Animal cells are affected by hydrodynamic forces that occur in culture vessel, transfer piping, and recovery operations such asmicrofiltration. Depending on the type, intensity, and duration of the force, and the specifics of the cell, the force may induce various kinds of responses in the subject cells. Both biochemical and physiological responses are observed, including apoptosis and purely mechanical destruction of the cell. This review examines the kinds of hydrodynamic forces encountered in bioprocessing equipment andthe impact of those forces on cells. Methods are given for quantifying the magnitude of the specific forces, and the response thresholds are noted for the common types of cells cultured in free suspension, supported on microcarriers, and anchored to stationary surfaces. KEY WORDS: animal cell culture, bioreactors cell damage, erythrocytes, shear effects.

I. INTRODUCTION Human and animal cellcultures are widely used to produce vaccines, therapeutic proteins, and diagnostic antibodies.1,2 Advances in tissue regeneration from in vitro cultured cells promise to further expand the demand for cell culture processes, and additional explosive growth is likely as methods are established for generating functional organs such as heart and kidney from cells. Cells are delicate. Culture andprocessing of cells invariably expose them to variously intense hydrodynamic forces. A sufficiently intense force will destroy cells outright, while a force of lesser magnitude may induce various physiological responses, including death, without necessarily causing any obvious physical damage. This review examines the nature of the forces encountered in bioprocessing and the effects of these forces on...