, Volume 62, Issue 5, pp 423–430 | Cite as

Comparing BRIN-BD11 culture producing insulin using different type of microcarriers

  • Maizirwan MelEmail author
  • Mohamed Ismail Abdul Karim
  • Siti Aisyah Mohd Yusuf
  • Yumi Zuhanis Has-Yun Hashim
  • Yusilawati Ahmad Nor
Original Research


This research was conducted to examine the growth profile, growth kinetics, and insulin-secretory responsiveness of BRIN-BD11 cells grown in optimized medium on different types of microcarriers (MCs). Comparisons were made on modified polystyrene (Hillex® II) and crosslinked polystyrene Plastic Plus (PP) from Solohill Engineering. The cell line producing insulin was cultured in a 25 cm2 T-flask as control while MCs based culture was implemented in a stirred tank bioreactor with 1 L working volume. For each culture type, the viable cell number, glucose, lactate, glutamate, and insulin concentrations were measured and compared. Maximum viable cell number was obtained at 1.47 × 105 cell/mL for PP microcarrier (PPMCs) culture, 1.35 × 105 cell/mL Hillex® II (HIIMCs) culture and 0.95 × 105 cell/mL for T-flask culture, respectively. The highest insulin concentration has been produced in PPMCs culture (5.31 mg/L) compared to HIIMCs culture (2.01 mg/L) and T-flask culture (1.99 mg/L). Therefore overall observation suggested that PPMCs was likely preferred to be used for BRIN-BD11 cell culture as compared with Hillex® II MCs.


Insulin BRIN-BD11 Solohill Microcarrier Bioreactor 



This project was funded by International Islamic University Malaysia (IIUM) Research Centre under Project Number LT 28/IIUM. Thank you for all contributors for this project especially for the staff of Laboratory of Cell and Tissue Engineering, Biotechnology Engineering Department of IIUM.


  1. Altamirano C, Illanes A, Becerra S, Cairo JJ, Godia F (2006) Considerations on the lactate consumption by CHO cells in the presence of galactose. J Biotech 125:547–556. doi: 10.1016/j.jbiotec.2006.03.023 CrossRefGoogle Scholar
  2. Amoli MM, Moosavizadeh R, Larijani B (2005) Optimizing conditions for rat pancreatic islets isolation. Cytotechnology 48:75–78. doi: 10.1007/s10616-005-3586-5 CrossRefGoogle Scholar
  3. Ball AJ, Flatt PR, McClenaghan NH (2000) Stimulation of insulin secretion in clonal BRIN-BD11 cells by the imidazoline derivatives KU14r and RX801080. Pharmacol Res 42:575–579. doi: 10.1006/phrs.2000.0739 CrossRefGoogle Scholar
  4. Batt BC, Kompala DS (1989) A structured kinetic modeling framework for the dynamics of hybridoma growth and monoclonal antibody production in continuous suspension cultures. Biotechnol Bioeng 34:515–531. doi: 10.1002/bit.260340412 CrossRefGoogle Scholar
  5. Bluml G (2007) Microcarrier cell culture technology. In: Portner R (ed) Animal cell biotechnology: methods and protocols. Humana Press, New Jersey, pp 149–179CrossRefGoogle Scholar
  6. Brennan L, Shine A, Hewage C, Malthouse JPG, Brindle KM, McClenaghan NH, Flatt PR, Newsholme P (2002) A NMR based demonstration of substantial oxidative l-alanine metabolism and l-alanine enhanced glucose metabolism in a clonal pancreatic β cell line—metabolism of l-alanine is important to the regulation of insulin secretion. Diabetes 51:1714–1721. doi: 10.2337/diabetes.51.6.1714 CrossRefGoogle Scholar
  7. Butler M (2004) Animal cell culture technology. BIOS Scientific Publishers, LondonCrossRefGoogle Scholar
  8. Butler M (2005) Animal cell cultures: recent achievements and perspectives in the production of biopharmaceuticals. App Microbiol Biotechnol 68:283–291. doi: 10.1007/s00253-005-1980-8 CrossRefGoogle Scholar
  9. Cooke MJ, Phillips SR, Shah DSH, Athey D, Lakey JH, Przyborski SA (2008) Enhanced cell attachment using a novel cell culture surface presenting functional domains from extracellular matrix proteins. Cytotechnology 56:71–79. doi: 10.1007/s10616-007-9119-7 CrossRefGoogle Scholar
  10. Dixon G, Nolan J, McClenaghan N, Flatt PR, Newsholme P (2003) A comparative study of amino acid consumption by rat islet cells and the clonal beta-cell line BRIN-BD11—the functional significance of l-alanine. J Endocrinol 179:447–454. doi: 10.1677/joe.0.1790447 CrossRefGoogle Scholar
  11. Finbarr PM, OHarte FPM, Hunter K, Gault VA, Irwin N, Green BD, Greer B, Harriott P, Bailey CJ, Flatt PR (2007) Antagonistic effects of two novel GIP analogs, (Hyp3)GIP and (Hyp3)GIPLys16PAL, on the biological actions of GIP and longer-term effects in diabetic ob/ob mice. Am J Physiol Endocrinol Metab 292:E1674–E1682. doi: 10.1152/ajpendo.00391 CrossRefGoogle Scholar
  12. Freshney RI (2006) Basic principles of cell culture. In: Novakovic GV, Freshney RI (eds) Culture of cells for tissue engineering. Wiley, Scotland, pp 1–22Google Scholar
  13. Grinnell F, Hays DG, Minter D (1977) Cell adhesion and spreading factor partial purification and properties. Exp Cell Res 110:175–190. doi: 10.1016/0014-4827(77)90284-1 CrossRefGoogle Scholar
  14. Groot M (1995) Microcarrier technology, present status and perspective. Cytotechnology 18:51–56. doi: 10.1007/BF00744319 CrossRefGoogle Scholar
  15. Hu WS, Wang DIC (2004) Selection of microcarrier diameter for the cultivation of mammalian cells on microcarriers. Biotechnol Bioeng 30:548–557. doi: 10.1002/bit.260300412 CrossRefGoogle Scholar
  16. Julien J (2003) Hydrodynamics, mass transfer and rheological studies of Gibberellic acid production in a stirred tank Bioreactor. World J Microb Biot 23:615–662Google Scholar
  17. Markvicheva E, Grandfils C (2004) Microcarriers for animal cell culture. In: Nedovic VA (ed) Fundamentals of cell immobilisation biotechnology. Kluwer, The Netherlands, pp 141–161Google Scholar
  18. McClenaghan NH (2007) Physiological regulation of the pancreatic β-cell: functional insights for understanding and therapy of diabetes. Exp Physiol 92:481–496. doi: 10.1113/expphysiol.2006.034835 CrossRefGoogle Scholar
  19. McClenaghan NH, Flatt PR (1999a) Engineering cultured insulin-secreting pancreatic B-cell lines. J Mol Med 77:235–243. doi: 10.1007/s001090050344 CrossRefGoogle Scholar
  20. McClenaghan NH, Flatt PR (1999b) Physiological and pharmacological regulation of insulin release: insights offered through exploitation of insulin-secreting cell lines. Diabetes Obes Metab 1: 1–14. PMID: 11220292Google Scholar
  21. Mendonca RZ, Pereira CA (1998) Cell metabolism and medium perfusion in Vero cell cultures on microcarriers in a bioreactor. Bioprocess Eng 18:213–228. doi: 10.1007/s004490050433 CrossRefGoogle Scholar
  22. Mendonca RZ, Arrozio SJ, Antoniazzi MM, Ferreira JMC Jr, Pereira CA (2002) Metabolic active-high density VERO cell cultures on microcarriers following apoptosis prevention by galactose/glutamine feeding. J Biotechnol 97:13–22. doi: 10.1016/S0168-1656(02)00048-2 CrossRefGoogle Scholar
  23. Newsholme P, Bender K, Kiely A, Brennan L (2007) Amino acid metabolism, insulin secretion and diabetes. Biochem Soc Trans 35:1180–1186. doi: 10.1042/BST0351180 CrossRefGoogle Scholar
  24. Phillips BW, Horne R, Lay TS, Rust WL, Teck TT, Crook JM (2008) Attachment and growth of human embryonic stem cells on microcarriers. J Biotechnol 138:24–32. doi: 10.1016/j.jbiotec.2008.07.1997 CrossRefGoogle Scholar
  25. Rourou S, Ark A, Velden T, Kallel H (2007) A microcarrier cell culture process for propagating rabies virus in Vero cells grown in a stirred bioreactor under fully animal component free conditions. Vaccine 25:3879–3889. doi: 10.1016/j.vaccine.2007.01.086 CrossRefGoogle Scholar
  26. Scheirer W, Merten OW (1991) Instrumentation of animal cell culture reactors. In: Ho CS, Wang DIC (eds) Animal cell bioreactors. Boston, Butterworth-Heinemann, pp 405–443Google Scholar
  27. Smetana K (1999) Cell biology of hydrogels. Biomaterials 14:1046–1050. doi: 10.1016/0142-9612(93)90203-E CrossRefGoogle Scholar
  28. Solo Hill Engineering Inc (2007) Solo Hill microcarrier beads. Solohill Engineering Inc, MichiganGoogle Scholar
  29. van Wezel AL (1976) Growth of cell-strains and primary cells on micro-carriers in homogeneous culture. Nature 216:64–65Google Scholar
  30. Varani J, Josephs S, Hillegas W (1996) Human diploid fibroblast growth on polystyrene microcarriers in aggregates. Cytotechnology 22:111–117. doi: 10.1007/BF00353930 CrossRefGoogle Scholar
  31. Varani J, Piel F, Josephs S, Beals TF, Hillegas WJ (1998) Attachment and growth of anchorage-dependent cells on a novel, charged-surface microcarrier under serum-free conditions. Cytotechnology 28:101–109. doi: 10.1023/A:1008029715765 CrossRefGoogle Scholar
  32. White LA, Ades EW (1990) Growth of Vero E-6 cells on microcarriers in a cell bioreactor. J Clin Microbiol 28: 283–286. PMCID: PMC269591Google Scholar
  33. Zahid MZA, Yusof F, Karim MIA (2008) Effect of d-glucose and l-glutamine in BRIN-BD11 insulinoma cell culture growth and insulin production. 4th Kuala Lumpur Int Conf Biomed Eng 21:810–813. doi: 10.1007/978-3-540-69139-6 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Maizirwan Mel
    • 1
    Email author
  • Mohamed Ismail Abdul Karim
    • 1
  • Siti Aisyah Mohd Yusuf
    • 1
  • Yumi Zuhanis Has-Yun Hashim
    • 1
  • Yusilawati Ahmad Nor
    • 1
  1. 1.Bioprocess and Molecular Engineering Research Unit, Department of Biotechnology Engineering, Faculty of EngineeringInternational Islamic University MalaysiaKuala LumpurMalaysia

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