Albumin and mammalian cell culture: implications for biotechnology applications

Albumin has a long historical involvement in design of media for the successful culture of mammalian cells, in both the research and commercial fields. The potential application of albumins, bovine or human serum albumin, for cell culture is a by-product of the physico-chemical, biochemical and cell-specific properties of the molecule. In this review an analysis of these features of albumin leads to a consideration of the extracellular and intracellular actions of the molecule, and importantly the role of its interactions with numerous ligands or bioactive factors that influence the growth of cells in culture: these include hormones, growth factors, lipids, amino acids, metal ions, reactive oxygen and nitrogen species to name a few. The interaction of albumin with the cell in relation to these co-factors has a potential impact on metabolic and biosynthetic activity, cell proliferation and survival. Application of this knowledge to improve the performance in manufacturing biotechnology and in the emerging uses of cell culture for tissue engineering and stem cell derived therapies is an important prospect.

[1]  J. Chalmers,et al.  Fabrication and use of a transient contractional flow device to quantify the sensitivity of mammalian and insect cells to hydrodynamic forces , 2002, Biotechnology and bioengineering.

[2]  M. Brady,et al.  Structural Origins of the Insulin-mimetic Activity of Bis(acetylacetonato)oxovanadium(IV)* , 2002, The Journal of Biological Chemistry.

[3]  A. Theriault,et al.  Human serum albumin and its structural variants mediate cholesterol efflux from cultured endothelial cells. , 2003, Biochimica et biophysica acta.

[4]  S. Pandey,et al.  Involvement of insulin-like growth factor type 1 receptor and protein kinase Cdelta in bis(maltolato)oxovanadium(IV)-induced phosphorylation of protein kinase B in HepG2 cells. , 2006, Biochemistry.

[5]  W. Stremmel,et al.  A new concept of cellular uptake and intracellular trafficking of long-chain fatty acids , 2001, Lipids.

[6]  S. Curry,et al.  Location of high and low affinity fatty acid binding sites on human serum albumin revealed by NMR drug-competition analysis. , 2006, Journal of molecular biology.

[7]  V. Venditti,et al.  Protein–thiol substitution or protein dethiolation by thiol/disulfide exchange reactions: The albumin model , 2007, Proteins.

[8]  P. Sadler,et al.  Structure, Properties, and Engineering of the Major Zinc Binding Site on Human Albumin* , 2009, The Journal of Biological Chemistry.

[9]  F. Sotgia,et al.  A Novel Role for Caveolin-1 in B Lymphocyte Function and the Development of Thymus-Independent Immune Responses , 2006, Cell cycle.

[10]  R. Yumoto,et al.  Low-affinity transport of FITC-albumin in alveolar type II epithelial cell line RLE-6TN. , 2008, Drug metabolism and pharmacokinetics.

[11]  Z. Upton,et al.  Serum-free primary human fibroblast and keratinocyte coculture. , 2010, Tissue engineering. Part A.

[12]  R. Yumoto,et al.  Mechanism of insulin uptake in rat alveolar type II and type I-like epithelial cells. , 2009, Biological & pharmaceutical bulletin.

[13]  E. Papoutsakis.  From CHO-Cell to Stem-Cell Biotechnology, Oxygenation, and Mixing in Animal-Cell Culture : Bioreactors, Bubbles, and Cell Injury , 2009 .

[14]  T. Peters,et al.  All About Albumin: Biochemistry, Genetics, and Medical Applications , 1995 .

[15]  K. Cheeseman,et al.  The effect of oxidative stress on the production of the recombinant protein, interferon γ, produced by Chinese hamster ovary cells in stirred-batch culture , 1997, Applied Microbiology and Biotechnology.

[16]  H. Klassen,et al.  Vitreous humor and albumin augment the proliferation of cultured retinal precursor cells , 2009, Journal of neuroscience research.

[17]  Yi-Hsuan Ho,et al.  Copper is taken up efficiently from albumin and alpha‐2‐macroglobulin by cultured human cells by more than one mechanism , 2008, American journal of physiology. Cell physiology.

[18]  J. Pedraz,et al.  Evaluation of human serum albumin as a substitute of foetal bovine serum for cell culture. , 2006, International journal of pharmaceutics.

[19]  D. Pearl,et al.  The Major Histocompatibility Complex–related Fc Receptor for IgG (FcRn) Binds Albumin and Prolongs Its Lifespan , 2003, The Journal of experimental medicine.

[20]  G. Schwartz,et al.  Apoptotic Response to Albumin Overload: Proximal vs. Distal/Collecting Tubule Cells , 2005, American Journal of Nephrology.

[21]  Edmond Lam,et al.  New insights into the interactions of serum proteins with bis(maltolato)oxovanadium(IV): transport and biotransformation of insulin-enhancing vanadium pharmaceuticals. , 2005, Journal of the American Chemical Society.

[22]  M. Ellmerer,et al.  Measurement of interstitial albumin in human skeletal muscle and adipose tissue by open-flow microperfusion. , 2000, American journal of physiology. Endocrinology and metabolism.

[23]  R. Quigg,et al.  Inhibition of NF-kappaB-dependent Bcl-xL expression by clusterin promotes albumin-induced tubular cell apoptosis. , 2008, Kidney international.

[24]  E. Bourdon,et al.  Differential effects of cysteine and methionine residues in the antioxidant activity of human serum albumin , 2005, Free radical research.

[25]  A. Baba,et al.  Degradation of oxidative stress-induced denatured albumin in rat liver endothelial cells. , 2005, American journal of physiology. Cell physiology.

[26]  M. Schiller,et al.  Hypothesis: human serum-borne albumin bound lipids promote cellular survival after apoptosis induction by a variety of stimuli , 2008, Apoptosis.

[27]  O. Merten.  Development of serum-free media for cell growth and production of viruses/viral vaccines--safety issues of animal products used in serum-free media. , 2002, Developments in biologicals.

[28]  E. Bourdon,et al.  The antioxidant properties of serum albumin , 2008, FEBS letters.

[29]  D C Carter,et al.  Structure of serum albumin. , 1994, Advances in protein chemistry.

[30]  M. Rao,et al.  Developing safe therapies from human pluripotent stem cells , 2009, Nature Biotechnology.

[31]  Sandra L. Schmid,et al.  Conserved Functions of Membrane Active GTPases in Coated Vesicle Formation , 2009, Science.

[32]  K. Nilausen.  Role of fatty acids in growth‐promoting effect of serum albumin on hamster cells in vitro , 1978, Journal of cellular physiology.

[33]  R. G. Ham,et al.  Albumin Replacement by Fatty Acids in Clonal Growth of Mammalian Cells , 1963, Science.

[34]  D. Rowe,et al.  Albumin facilitates zinc acquisition by endothelial cells. , 2000, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[35]  Y. Chisti,et al.  Hydrodynamic Damage to Animal Cells , 2001, Critical reviews in biotechnology.

[36]  H. Sirén,et al.  Determination of association constants between steroid compounds and albumins by partial‐filling ACE , 2007, Electrophoresis.

[37]  Simon C Watkins,et al.  A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors. , 2006, Molecular biology of the cell.

[38]  M. Haratake,et al.  Albumin-mediated selenium transfer by a selenotrisulfide relay mechanism. , 2008, Inorganic chemistry.

[39]  M. Yap,et al.  Zinc as an insulin replacement in hybridoma cultures. , 2006, Biotechnology and bioengineering.

[40]  S. Foley,et al.  Reductive unfolding of serum albumins uncovered by Raman spectroscopy. , 2008, Biopolymers.

[41]  Y. Marcel,et al.  Serum albumin is a significant intermediate in cholesterol transfer between cells and lipoproteins. , 1996, Biochemistry.

[42]  M. Gresser,et al.  Mechanism of Inhibition of Protein-tyrosine Phosphatases by Vanadate and Pervanadate* , 1997, The Journal of Biological Chemistry.

[43]  J. Andersen,et al.  The versatile MHC class I-related FcRn protects IgG and albumin from degradation: implications for development of new diagnostics and therapeutics. , 2009, Drug metabolism and pharmacokinetics.

[44]  W. Kessler,et al.  Comparison of a Production Process in a Membrane‐Aerated Stirred Tank and up to 1000‐L Airlift Bioreactors Using BHK‐21 Cells and Chemically Defined Protein‐Free Medium , 2003, Biotechnology progress.

[45]  J. Uličný,et al.  Influence of structure of human, rat, and bovine serum albumins on binding properties of photoactive drug hypericin. , 2002, Biopolymers.

[46]  H. Yamazoe,et al.  Preparation of water-insoluble albumin film possessing nonadherent surface for cells and ligand binding ability. , 2008, Journal of biomedical materials research. Part A.

[47]  R. Minshall,et al.  Vesicle formation and endocytosis: function, machinery, mechanisms, and modeling. , 2009, Antioxidants & redox signaling.

[48]  D. Summa,et al.  Biochemical and biological aspects of protein thiolation in cells and plasma. , 2005, Antioxidants & redox signaling.

[49]  A. Velasco,et al.  Megalin is a receptor for albumin in astrocytes and is required for the synthesis of the neurotrophic factor oleic acid , 2008, Journal of neurochemistry.

[50]  B. Halliwell,et al.  Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? , 2004, British journal of pharmacology.

[51]  C. Hubel,et al.  Binding of fatty acids facilitates oxidation of cysteine-34 and converts copper-albumin complexes from antioxidants to prooxidants. , 2003, Archives of biochemistry and biophysics.

[52]  Y. Chisti,et al.  Animal-cell damage in sparged bioreactors. , 2000, Trends in biotechnology.

[53]  E. Papoutsakis,et al.  Damage mechanisms of suspended animal cells in agitated bioreactors with and without bubble entrainment , 2009, Biotechnology and bioengineering.

[54]  M. Moo-young,et al.  Effects of the hydrodynamic environment and shear protectants on survival of erythrocytes in suspension. , 1995, Journal of biotechnology.

[55]  M. Connelly,et al.  Lipid transporters: membrane transport systems for cholesterol and fatty acids. , 2000, Current opinion in clinical nutrition and metabolic care.

[56]  P. Greenfield,et al.  Mechanical agitation of hybridoma suspension cultures: Metabolic effects of serum, pluronic F68, and albumin supplements , 1992, Biotechnology and bioengineering.

[57]  Merten Ow.  Development of serum-free media for cell growth and production of viruses/viral vaccines--safety issues of animal products used in serum-free media. , 2002 .

[58]  E. Tibaduiza,et al.  Zinc transport across an endothelium includes vesicular cotransport with albumin , 1996, Journal of cellular physiology.

[59]  E. Stanley,et al.  A protocol describing the use of a recombinant protein-based, animal product-free medium (APEL) for human embryonic stem cell differentiation as spin embryoid bodies , 2008, Nature Protocols.

[60]  Ruben Godoy-Silva,et al.  Acute hydrodynamic forces and apoptosis: A complex question , 2007, Biotechnology and bioengineering.

[61]  R. Yumoto,et al.  Clathrin-mediated endocytosis of FITC-albumin in alveolar type II epithelial cell line RLE-6TN. , 2006, American journal of physiology. Lung cellular and molecular physiology.

[62]  D. Leavesley,et al.  A chimeric vitronectin: IGF-I protein supports feeder-cell-free and serum-free culture of human embryonic stem cells. , 2010, Stem cells and development.

[63]  David Barnes,et al.  Serum-free cell culture: a unifying approach , 1980, Cell.

[64]  P. Brick,et al.  Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites , 1998, Nature Structural Biology.

[65]  M. Al‐Rubeai,et al.  Death mechanisms of animal cells in conditions of intensive agitation , 1995, Biotechnology and bioengineering.

[66]  J. Andersen,et al.  The conserved histidine 166 residue of the human neonatal Fc receptor heavy chain is critical for the pH‐dependent binding to albumin , 2006, European journal of immunology.

[67]  E. Stanley,et al.  ErythRED, a hESC line enabling identification of erythroid cells , 2009, Nature Methods.

[68]  L. Liaudet,et al.  Nitric oxide and peroxynitrite in health and disease. , 2007, Physiological reviews.

[69]  Martin Clynes,et al.  The role of recombinant proteins in the development of serum-free media , 2006, Cytotechnology.

[70]  Johannes G Khinast,et al.  Characterization of the localized hydrodynamic shear forces and dissolved oxygen distribution in sparged bioreactors , 2007, Biotechnology and bioengineering.

[71]  P. Domingues,et al.  Oxidation of bovine serum albumin: identification of oxidation products and structural modifications. , 2009, Rapid communications in mass spectrometry : RCM.

[72]  Alan T. Bull,et al.  CHO cell growth and recombinant interferon-γ production: Effects of BSA, Pluronic and lipids , 2004, Cytotechnology.

[73]  W. Bal,et al.  Human serum albumin coordinates Cu(II) at its N-terminal binding site with 1 pM affinity , 2007, JBIC Journal of Biological Inorganic Chemistry.

[74]  M. Clynes,et al.  Separation of growth-stimulating activity of BSA fraction V from the bulk of albumin using Heparin Sepharose Chromatography , 2004, Cytotechnology.

[75]  R. Yumoto,et al.  Comparison of Albumin Uptake in Rat Alveolar Type II and Type I-like Epithelial Cells in Primary Culture , 2008, Pharmaceutical Research.

[76]  R. Pagano,et al.  Distinct mechanisms of clathrin-independent endocytosis have unique sphingolipid requirements. , 2006, Molecular biology of the cell.

[77]  G. Gerber,et al.  A direct role for serum albumin in the cellular uptake of long-chain fatty acids. , 1995, The Biochemical journal.

[78]  O. Merten,et al.  Introduction to animal cell culture technology—past, present and future , 2006, Cytotechnology.

[79]  W. Stremmel,et al.  Translocation of long chain fatty acids across the plasma membrane – lipid rafts and fatty acid transport proteins , 2006, Molecular and Cellular Biochemistry.

[80]  T. Akaike,et al.  S-Nitrosylated Human Serum Albumin-mediated Cytoprotective Activity Is Enhanced by Fatty Acid Binding* , 2008, Journal of Biological Chemistry.

[81]  S. Curry,et al.  Crystal structures of human serum albumin complexed with monounsaturated and polyunsaturated fatty acids. , 2001, Journal of molecular biology.

[82]  M. Gay,et al.  Characterization of peptides and proteins in commercial HSA solutions , 2010, Proteomics.

[83]  W. Guggino,et al.  PKB and megalin determine the survival or death of renal proximal tubule cells , 2006, Proceedings of the National Academy of Sciences.

[84]  Sandra L. Schmid,et al.  Regulated portals of entry into the cell , 2003, Nature.

[85]  P. C. Chau,et al.  Serum‐free media in hybridoma culture and monoclonal antibody production , 1988, Biotechnology and bioengineering.

[86]  M. Yap,et al.  Evaluation of insulin-mimetic trace metals as insulin replacements in mammalian cell cultures , 2004, Cytotechnology.

[87]  Jack T. H. Wang,et al.  A role for SNX5 in the regulation of macropinocytosis , 2008, BMC Cell Biology.

[88]  R. Stauber,et al.  Physiological and pathological changes in the redox state of human serum albumin critically influence its binding properties , 2007, British journal of pharmacology.

[89]  M. Clynes,et al.  Recombinant Human Albumin in Cell Culture: Evaluation of Growth-Promoting Potential for NRK and SCC-9 Cells In Vitro , 1997, Cytotechnology (Dordrecht).

[90]  H. Yamazoe,et al.  Facile cell patterning on an albumin-coated surface. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[91]  J. Chalmers,et al.  Physiological responses of CHO cells to repetitive hydrodynamic stress , 2009, Biotechnology and bioengineering.

[92]  E. Stanbridge,et al.  Frontiers in mammalian cell culture. , 1990, In vitro cellular & developmental biology : journal of the Tissue Culture Association.

[93]  E. Papoutsakis,et al.  Damage mechanisms of suspended animal cells in agitated bioreactors with and without bubble entrainment , 1990, Biotechnology and bioengineering.

[94]  W. Zawalich,et al.  Enhanced activation of phospholipase C and insulin secretion from islets incubated in fatty acid-free bovine serum albumin. , 2008, Metabolism: clinical and experimental.

[95]  J. I. Izpisúa Belmonte,et al.  Albumin-Associated Lipids Regulate Human Embryonic Stem Cell Self-Renewal , 2008, PloS one.

[96]  L. Liaudet,et al.  Role of peroxynitrite in the redox regulation of cell signal transduction pathways. , 2009, Frontiers in bioscience.

[97]  T. Akaike,et al.  Effects of endogenous ligands on the biological role of human serum albumin in S-nitrosylation. , 2007, Biochemical and biophysical research communications.

[98]  W. Stremmel,et al.  Uptake of long chain fatty acids is regulated by dynamic interaction of FAT/CD36 with cholesterol/sphingolipid enriched microdomains (lipid rafts) , 2008, BMC Cell Biology.

[99]  W. Stremmel,et al.  Cellular uptake of fatty acids driven by the ER-localized acyl-CoA synthetase FATP4 , 2006, Journal of Cell Science.

[100]  D. C. Carter,et al.  Atomic structure and chemistry of human serum albumin , 1993, Nature.

[101]  S. Paek,et al.  Human Microglial Cells Synthesize Albumin in Brain , 2008, PloS one.

[102]  D. Kehoe,et al.  Scalable stirred-suspension bioreactor culture of human pluripotent stem cells. , 2010, Tissue engineering. Part A.

[103]  M. Al‐Rubeai,et al.  Using cell engineering and omic tools for the improvement of cell culture processes , 2007, Cytotechnology.

[104]  G. Martin,et al.  Albumin: Biochemical properties and therapeutic potential , 2005, Hepatology.

[105]  Mustafa Arici,et al.  Stimulation of proximal tubular cell apoptosis by albumin-bound fatty acids mediated by peroxisome proliferator activated receptor-gamma. , 2003, Journal of the American Society of Nephrology : JASN.

[106]  J. Woodard,et al.  Specific binding proteins for selenium in rat tissues. , 1988, Carcinogenesis.

[107]  Bill X. Huang,et al.  Probing three-dimensional structure of bovine serum albumin by chemical cross-linking and mass spectrometry , 2004, Journal of the American Society for Mass Spectrometry.

[108]  E. Benedetti,et al.  Increased Albumin Concentration Reduces Apoptosis and Improves Functionality of Human Islets , 2008, Artificial cells, blood substitutes, and immobilization biotechnology.

[109]  Satyajit Mayor,et al.  Pathways of clathrin-independent endocytosis , 2007, Nature Reviews Molecular Cell Biology.

[110]  H. Zoellner,et al.  The Anti-Apoptotic Activity of Albumin for Endothelium Is Mediated by a Partially Cryptic Protein Domain and Reduced by Inhibitors of G-Coupled Protein and PI-3 Kinase, but Is Independent of Radical Scavenging or Bound Lipid , 2007, Journal of Vascular Research.

[111]  Renate Kunert,et al.  Analysis of immunoglobulin glycosylation by LC‐ESI‐MS of glycopeptides and oligosaccharides , 2008, Proteomics.

[112]  B. Barisas,et al.  Effects of Vanadium‐Containing Compounds on Membrane Lipids and on Microdomains Used in Receptor‐Mediated Signaling , 2008, Chemistry & biodiversity.