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Encyclopedia of Physical Science and Technology EN009G-399 July 6, 2001 20:4

Mammalian Cell Culture 33

TABLE I Mammalian Cell Products
Native products Product name (Year of license)
Human vaccines Polio (1954), measles (1963), rabies (1964), mumps (1969)
Veterinary vaccines FMDV, rabies, Marek’s, pseudorabies, BVD, Louping ill,
bluetongue, avian influenza, canine distemper
Interferon
Recombinant products
Monoclonal antibodies OKT3/Orthoclone (1987), Centoxin (1990), Reopro (1994),
Myoscint (1989), Oncoscint (1990)
tPA Activase/Actilyse (1987)
EPO Epogen/Procrit/Eprex (1989), Epogin/Recormon (1990)
hGH Saizen (1989)
HBsAg GenHevac B Pasteur (1989), HBGamma (1990)
Interferon Roferon(1991)
G-CSF Granocyte (1991), Neupogen (1991)
Blood factor VIII Recombinate (1992), Kogenate (1993)
Dnase I Pulmozyme (1993)
Glucocerebrosiduse Cerezyme (1994)
FSH Gonal-F (1995)
rDNA products in development/clinical trial
HIV vaccines (gp120, gp160, CD4)
Herpes simplex vaccines (gB,gD)
Chimeric Mabs (her2, CD4, TNFα, CD20, Cd18, TAC,
leukointegrin, CF54, RSV)
In vitro diagnostic Mabs (over 200)
Others (TSH, TNF, M-CSF, IL-6, IL-1)
Tissue engineering and replacement (e.g., skin, artificial
liver, kidneys)

has been the development of more efficient culture media Cells can be grown as:
(particularly the identification of specific growth factors
that have allowed the introduction of serum-free and low- 1. Organculture:Short-termcultureoffunctionaltissue
protein media and thus the growth of specialized rather (e.g., tissue slices).
than undifferentiated cells), followed by cell fusion tech- 2. Primary cells: Short-term culture of single cells iso-
niques (e.g., hybridomas) and recombinant DNA technol- lated directly from tissues, usually by an enzymic treat-
ogy to allow product expression from fast-growing undif- ment, and allowed to grow and divide until they are ready
ferentiated cells and to enhance productivity. for subculturing into daughter cultures as a cell line. How-
ever, for many applications, cells are only used in the pri-
mary culture as they still retain some in vitro specialized
characteristics (e.g., chick embryo fibroblasts and monkey
II. THE CELL kidney cells) for vaccine manufacture.
3. Finite cell lines: Cells derived from normal tissue via
A. Cell Types a primary culture which can replicate and undergo lim-
ited subculture until they become senescent (e.g., WI-38,
A cell culture is usually initiated by the explant technique MRC-5) or immortalized (by chemical carcinogens, trans-
(allowing cells to migrate out of a tissue fragment to form
forming viruses, hybridization, or genetic engineering).
a culture of individual cells) or by mechanically and en-
4. Continuous cell lines: Cells that have an indefinite
zymically breaking down an organ/tissue into single cells
subculture potential derived from tumour tissue (e.g.,
which are then plated out as a primary culture. A complex
HeLa) or that have undergone immortalization in vitro
medium of amino acids, vitamins, salts, glucose, and fetal
(e.g., L929 cells).
calf serum (or a range of growth factors normally present
◦
in serum), buffered at pH 7.0 to 7.4, and incubated at 37 C Finite cell lines have been extensively used in vaccine
is necessary to isolate and cultivate cells. production but they are limited in cell type (usually