Cell culture

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Inside of a CO 2 incubator with cell culture plates and bottles

When cell culture is the cultivation of animal or plant cells in a nutrient medium outside the organism referred to. Cell lines are cells of one type of tissue that can reproduce indefinitely in the course of this cell culture. Both immortalized (immortal) cell lines and primary cells are cultivated (primary culture). A primary culture is a non-immortalized cell culture that was obtained directly from a tissue. Cell cultures are widely used in biological and medical research, development and production.


Since the beginning of scientific research, there have been efforts to keep cells and tissue alive outside of an organism in order to be able to examine them more closely. Wilhelm Roux succeeded for the first time in 1885 in keeping embryonic chicken cells alive for several days in a saline solution, thus demonstrating the basic principle. In 1913, Alexis Carrel showed that cells can grow longer in cell culture as long as they are fed and kept aseptic .

The oldest animal cell line is believed to be sticker sarcoma , an infectious tumor of natural origin that arose around 200 to 11,000 years ago. Since its inception, sticker sarcoma has accumulated around 1.9 million mutations , and 646 genes have been deleted .

In the years 1951/1952 an immortal human cell line from a cervical carcinoma was established for the first time , which later became known under the name HeLa . In the following decades, nutrient media, growth factors and conditions in particular were further developed and new cell lines were established. In 1975, César Milstein and Georges Köhler discovered the possibility of producing monoclonal antibodies through the fusion of lymphocytes with cancer cells using the hybridoma technique . For this discovery, they received the 1984 Nobel Prize in Physiology or Medicine . In addition, methods for the targeted introduction and expression of genes in cells, the so-called transfection , were developed during these years .

Body cells that have not yet differentiated - so-called stem cells - were first isolated in 1981 from the blastocysts of an embryonic mouse. They tend to differentiate spontaneously in vitro . This can be prevented by factors that promote the self-renewal of the cells. Several such substances have been identified since the late 1980s. Research in this field is currently focused on the cultivation and targeted differentiation of both embryonic and adult stem cells.


Most of the work with cells takes place in a cell culture laboratory . Primary cultures can be created from different tissues , for example from whole embryos or individual organs such as skin, kidneys, etc. The tissue is treated with a protease , for example trypsin , which breaks down the proteins that maintain the cell structure. This causes the cells to become isolated. By adding growth factors , certain cell types can be specifically stimulated to divide. For poorly growing cell types, feeder cells , basement membrane-like matrices and recombinant components of the extracellular matrix are also used.

The tumor cells removed from animal or human tissue are after initial growth on a nutrient medium by analysis of surface antigens ( immunocytology ) or the genome ( PCR and sequencing ) analyzed and selected in order to then bring a large tumor cell clone into culture. The cells can also be genetically modified by introducing a plasmid as a vector . Cells are removed from the stock culture and deep-frozen in liquid nitrogen and are then available for dispatch to other research institutions.

Most cells have a limited lifespan (limited by the Hayflick limit ), with the exception of some tumor-derived cells. After a certain number of doublings, these cells go into senescence and no longer divide. Established or immortal cell lines have acquired the ability to divide indefinitely - either through random mutation (in tumor cells) or through targeted changes (for example through the artificial expression of the telomerase gene).

A distinction is also made between cells that grow adherently (on surfaces), such as fibroblasts , endothelial cells or cartilage cells, and suspension cells that grow freely floating in the nutrient medium, such as lymphocytes . The culture conditions differ greatly between the individual cultured cell lines. The different cell types prefer different nutrient media that are specifically composed, for example different pH values ​​or concentrations of amino acids or nutrients. As a rule, mammalian cells grow at 37 ° C with an atmosphere of 5% CO 2 in special incubators. Depending on the rate of division and density of the cells, the cell clusters are loosened every few days and distributed to new vessels (called “passage” or “splitting”). The number of passages indicates the frequency with which the cells have already been passaged. In the case of adherent cells in continuous culture, the cells are regularly isolated in order to avoid confluence and the associated inhibition of cell contact .

Culture media are, for example, RPMI-1640 , Dulbecco's Modified Eagle Medium or Ham's F12 . Balanced salt solutions such as Hanks salts or Earle salts are used for washing and short-term storage (a few minutes) .


Cell cultures are widely used, particularly in research and development. The metabolism, division and many other cellular processes can thus be examined in basic research. Furthermore, cultivated cells are used as test systems, for example in the investigation of the effect of substances on the signal transduction and toxicity of the cell. This also drastically reduces the number of animal experiments .

Cell cultures of mammalian cells are also very important for the production of numerous biotechnical products. For example, monoclonal antibodies for research and therapeutic use in medicine are produced using cell culture. Although simple proteins can also be produced in bacteria with less effort, glycosylated proteins must be produced in cell culture, as this is the only place where the correct glycosylation of the proteins takes place. An example of this is erythropoietin (EPO). Many vaccines are also produced in cell culture. Bioreactors are used for the development and implementation of industrial cell culture processes , some in insect cell culture . Disposable bioreactors are of increasing interest for the production of biopharmaceutical products .

In the plant propagation is produced in the Vegetable tissue culture from cell cultures complete plants.

Cell culture lines

It should be noted that the following list of cell culture lines is incomplete. The ATCC alone has up to 4,000 cell lines.

Cell line meaning Origin species Origin tissue morphology link
293-T Contains plasmid with temperature-sensitive mutant of the simian virus 40 large T antigen human Kidney (embryo) derivative of HEK-293 epithelium DSMZ Cellosaurus
A431 human skin epithelium DSMZ Cellosaurus
A549 human Adenocarcinoma of the lungs epithelium DSMZ Cellosaurus
BCP-1 human blood lymphocyte ATCC Cellosaurus
bEnd.3 brain endothelial mouse Brain / cerebral cortex Endothelium ATCC Cellosaurus
BHK-21 syrian baby hamster kidney hamster Kidney (embryonic) Fibroblast DSMZ Cellosaurus
BxPC-3 human Pancreas , andean carcinoma epithelium DSMZ Cellosaurus
BY-2 Bright Yellow-2 tobacco Callus induced on the seedling DSMZ ( Memento from November 8, 2007 in the Internet Archive )
CHO Chinese hamster ovary hamster Ovaries epithelium ICLC Cellosaurus
COS-1 Originated from CV-1 cells by transformation of an origin-defective SV-40 Monkey - Chlorocebus aethiops ( Ethiopian green monkey ) kidney Fibroblast DSMZ Cellosaurus
COS-7 Originated from CV-1 cells by transformation of an origin-defective SV-40 Monkey - Chlorocebus aethiops kidney Fibroblast DSMZ Cellosaurus
CV-1 Monkey - Chlorocebus aethiops kidney Fibroblast Cellosaurus
EPC herpesviral induced papular epithelioma Fish ( Pimephales promelas ) skin epithelium ATCC Cellosaurus
HaCaT human adult, calcium, temperature human Keratinocyte epithelium Cellosaurus
HDMEC human dermal microvascular endothelial cells human foreskin Endothelium Journal of Investigative Dermatology
HEK-293 human embryonic kidney human Kidney (embryonic) epithelium DSMZ Cellosaurus
HeLa Henrietta Lacks human Cervical cancer ( cervical cancer ) epithelium DSMZ Cellosaurus
HepG2 human hepatocellular carcinoma human Hepatocellular carcinoma epithelium DSMZ Cellosaurus
HL-60 human leukemia human Promyeloblasts Blood cells DSMZ Cellosaurus
HMEC-1 immortalized human microvascular endothelial cells human foreskin Endothelium ATCC Cellosaurus
HUVEC human umbilical vein endothelial cells human Umbilical vein Endothelium ICLC
HT-1080 human Fibrosarcoma Connective tissue cells DSMZ Cellosaurus
Jurkat human T-cell leukemia Blood cells DSMZ Cellosaurus
K562 oldest human leukemia cell line human blood myeloid blood cells, established 1975 DSMZ Cellosaurus
LNCaP human Prostate adenocarcinoma epithelium DSMZ Cellosaurus
MCF-7 Michigan Cancer Foundation human Breast, adenocarcinoma epithelium DSMZ Cellosaurus
MCF-10A Michigan Cancer Foundation human Mammary gland epithelium ATCC Cellosaurus
MDCK Madin Darby canine kidney dog kidney epithelium ATCC Cellosaurus
MTD-1A mouse Mammary gland epithelium Cellosaurus
MyEnd myocardial endothelial mouse heart Endothelium Cellosaurus
Neuro-2A (N2A) Neuroblastoma mouse brain Neuroblast DSMZ Cellosaurus
NIH-3T3 NIH , 3-day transfer, inoculum 3 × 10 5 cells, contact-inhibited NIH Swiss mouse embryo mouse embryo Fibroblast DSMZ Cellosaurus
NTERA-2 cl.D1 [NT2 / D1] Pluripotent cell differentiable with tretinoin human Testicles , lung metastasis epithelium ATCC Cellosaurus
P19 Pluripotent cell differentiable with tretinoin mouse Embryonic carcinoma epithelium DSMZ Cellosaurus
PANC-1 pancreas 1 human Pancreas , adenocarcinoma epithelium DSMZ Cellosaurus
peer human T cell leukemia DSMZ Cellosaurus
RTL-W1 rainbow-trout liver - Waterloo 1 cells Rainbow trout - Oncorhynchus mykiss liver Fibroblast (likely) Cellosaurus
Sf-9 Spodoptera frugiperda Insect - Spodoptera frugiperda (moth) Ovary DSMZ Cellosaurus
Saos-2 Osteosarcoma human bone epithelium DSMZ Cellosaurus
T2 human T cell leukemia / B cell line hybridoma DSMZ Cellosaurus
T84 human Colorectal carcinoma / lung metastasis epithelium ATCC Cellosaurus
U-937 human Burkitt lymphoma monocytic DSMZ Cellosaurus

See also


  • Sabine Schmitz: The experimenter: cell culture . 1st edition. Spectrum Academic Publishing House, 2007, ISBN 978-3-8274-1564-6 .
  • Toni Lindl, Gerhard Gstraunthaler: Cell and tissue culture. From the basics to the laboratory bench. 6th edition. Spectrum Academic Publishing House, 2008, ISBN 978-3-8274-1776-3 .
  • WW Minuth, L. Denk: Advanced Culture Experiments with Adherent Cells. - From single cells to specialized tissues in perfusion culture. Open access publishing. University of Regensburg 2011, ISBN 978-3-88246-330-9 .

Individual evidence

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  2. ^ ID O'Neill: Concise review: transmissible animal tumors as models of the cancer stem-cell process. In: Stem Cells (2011), Volume 29 (12), pp. 1909-1914. doi: 10.1002 / stem.751 . PMID 21956952 .
  3. a b H. G. Parker, EA Ostrander: Hiding in Plain View-An Ancient Dog in the Modern World. In: Science. 343, 2014, pp. 376–378, doi: 10.1126 / science.1248812 .
  4. Landmarks
  5. ^ ATCC Cell Lines. Retrieved February 6, 2018 .
  6. Zbigniew Ruszczak, Michael Detmar u. a .: Effects of rIFN Alpha, Beta, and Gamma on the Morphology, Proliferation, and Cell Surface Antigen Expression of Human Dermal Microvascular Endothelial Cells In Vitro. In: Journal of Investigative Dermatology. 95, 1990, pp. 693-699, doi: 10.1111 / 1523-1747.ep12514496 .