Cell culture ortissue culture is the process by whichcells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have beenisolated from living tissue, they can subsequently be maintained under carefully controlled conditions. They need to be kept at body temperature (37 °C) in an incubator.[1] These conditions vary for each cell type, but generally consist of a suitable vessel with a substrate or richmedium that supplies the essential nutrients (amino acids,carbohydrates,vitamins,minerals),growth factors,hormones, and gases (CO2,O2), and regulates the physio-chemical environment (pH buffer,osmotic pressure,temperature). Most cells require a surface or an artificial substrate to form anadherent culture as a monolayer (one single-cell thick), whereas others can be grown free floating in a medium as asuspension culture.[2] This is typically facilitated via use of a liquid, semi-solid, or solidgrowth medium, such asbroth oragar. Tissue culture commonly refers to the culture of animal cells and tissues, with the more specific termplant tissue culture being used for plants. The lifespan of most cells is genetically determined, but some cell-culturing cells have been 'transformed' into immortal cells which will reproduce indefinitely if the optimal conditions are provided.
In practice, the term "cell culture" now refers to the culturing of cells derived from multicellulareukaryotes, especially animal cells, in contrast with other types of culture that also grow cells, such asplant tissue culture,fungal culture, andmicrobiological culture (ofmicrobes). The historical development and methods of cell culture are closely interrelated with those oftissue culture andorgan culture.Viral culture is also related, with cells as hosts for the viruses.
The laboratory technique of maintaining livecell lines (a population of cells descended from a single cell and containing the same genetic makeup) separated from their original tissue source became more robust in the middle 20th century.[3][4]
The 19th-century English physiologistSydney Ringer developedsalt solutions containing the chlorides of sodium, potassium, calcium and magnesium suitable for maintaining the beating of an isolatedanimal heart outside the body.[5] In 1885Wilhelm Roux removed a section of themedullary plate of anembryonicchicken and maintained it in a warmsaline solution for several days, establishing the basic principle of tissue culture. In 1907 the zoologistRoss Granville Harrison demonstrated the growth of frog embryonic cells that would give rise to nerve cells in a medium of clottedlymph. In 1913, E. Steinhardt, C. Israeli, and R. A. Lambert grewvacciniavirus in fragments of guinea pigcorneal tissue.[6] In 1996, the first use of regenerative tissue was used to replace a small length of urethra, which led to the understanding that the technique of obtaining samples of tissue, growing it outside the body without a scaffold, and reapplying it, can be used for only small distances of less than 1 cm.[7][8][9]Ross Granville Harrison, working atJohns Hopkins Medical School and then atYale University, published results of his experiments from 1907 to 1910, establishing the methodology oftissue culture.[10]
Gottlieb Haberlandt first pointed out the possibilities of the culture of isolated tissues,plant tissue culture.[11] He suggested that the potentialities of individual cells via tissue culture as well as that the reciprocal influences of tissues on one another could be determined by this method. Since Haberlandt's original assertions, methods for tissue and cell culture have been realized, leading to significant discoveries in biology and medicine. He presented his original idea oftotipotentiality in 1902, stating that "Theoretically all plant cells are able to give rise to a complete plant."[12][13][14] The termtissue culture was coined by American pathologistMontrose Thomas Burrows.[15]
Cell culture techniques were advanced significantly in the 1940s and 1950s to support research invirology. Growing viruses in cell cultures allowed preparation of purified viruses for the manufacture ofvaccines. The injectablepolio vaccine developed byJonas Salk was one of the first products mass-produced using cell culture techniques. This vaccine was made possible by the cell culture research ofJohn Franklin Enders,Thomas Huckle Weller, andFrederick Chapman Robbins, who were awarded aNobel Prize for their discovery of a method of growing the virus in monkeykidney cell cultures. Cell culture has contributed to the development of vaccines for many diseases.[1]
In modern usage, "tissue culture" generally refers to the growth of cells from a tissue from amulticellular organismin vitro. These cells may be cells isolated from a donor organism (primary cells) or animmortalised cell line. The cells are bathed in a culture medium, which contains essential nutrients and energy sources necessary for the cells' survival.[16] Thus, in its broader sense, "tissue culture" is often used interchangeably with "cell culture". On the other hand, the strict meaning of "tissue culture" refers to the culturing of tissue pieces, i.e.explant culture.
Tissue culture is an important tool for the study of the biology of cells from multicellular organisms. It provides anin vitro model of the tissue in a well defined environment which can be easily manipulated and analysed. In animal tissue culture, cells may be grown as two-dimensional monolayers (conventional culture) or within fibrous scaffolds or gels to attain more naturalistic three-dimensional tissue-like structures (3D culture). A 1988 NIH SBIR grant report showed that electrospinning could be used to produce nano- and submicron-scale polymeric fibrous scaffolds specifically intended for use asin vitro cell and tissue substrates. This early use of electrospun fibrous lattices for cell culture and tissue engineering showed that various cell types would adhere to and proliferate upon polycarbonate fibers. It was noted that as opposed to the flattened morphology typically seen in 2D culture, cells grown on the electrospun fibers exhibited a more rounded 3-dimensional morphology generally observed of tissuesin vivo.[17]
Plant tissue culture in particular is concerned with the growing of entire plants from small pieces of plant tissue, cultured in medium.[18]
Cells can beisolated from tissues forex vivo culture in several ways. Cells can be easily purified from blood; however, only thewhite cells are capable of growth in culture. Cells can be isolated from solid tissues by digesting the extracellular matrix usingenzymes such ascollagenase,trypsin, orpronase, before agitating the tissue to release the cells into suspension.[19][20] Alternatively, pieces of tissue can be placed ingrowth media, and the cells that grow out are available for culture. This method is known asexplant culture.
Cells that are cultured directly from a subject are known as primary cells. With the exception of some derived from tumors, mostprimary cell cultures have limited lifespan.
An established orimmortalized cell line has acquired the ability to proliferate indefinitely either through random mutation or deliberate modification, such as artificialexpression of thetelomerasegene.Numerous cell lines are well established as representative of particularcell types.
For the majority of isolated primary cells, they undergo the process ofsenescence and stop dividing after a certain number of population doublings while generally retaining their viability (described as theHayflick limit).
Aside from temperature and gas mixture, the most commonly varied factor in culture systems is the cellgrowth medium. Recipes for growth media can vary inpH, glucose concentration,growth factors, and the presence of other nutrients. The growth factors used to supplement media are often derived from the serum of animal blood, such asfetal bovine serum (FBS), bovine calf serum, equine serum, and porcine serum. One complication of these blood-derived ingredients is the potential for contamination of the culture with viruses orprions, particularly in medicalbiotechnology applications. Current practice is to minimize or eliminate the use of these ingredients wherever possible and use humanplatelet lysate (hPL).[21] This eliminates the worry of cross-species contamination when using FBS with human cells. hPL has emerged as a safe and reliable alternative as a direct replacement for FBS or other animal serum. In addition,chemically defined media can be used to eliminate any serum trace (human or animal), but this cannot always be accomplished with different cell types. Alternative strategies involve sourcing the animal blood from countries with minimumBSE/TSE risk, such as The United States, Australia and New Zealand,[22] and using purified nutrient concentrates derived from serum in place of whole animal serum for cell culture.[23]
Plating density (number of cells per volume of culture medium) plays a critical role for some cell types. For example, a lower plating density makesgranulosa cells exhibit estrogen production, while a higher plating density makes them appear asprogesterone-producingtheca lutein cells.[24]
Cells can be grown either insuspension oradherent cultures.[25] Some cells naturally live in suspension, without being attached to a surface, such as cells that exist in the bloodstream. There are also cell lines that have been modified to be able to survive in suspension cultures so they can be grown to a higher density than adherent conditions would allow. Adherent cells require a surface, such as tissue culture plastic ormicrocarrier, which may be coated with extracellular matrix (such as collagen and laminin) components to increase adhesion properties and provide other signals needed for growth and differentiation. Most cells derived from solid tissues are adherent. Another type of adherent culture isorganotypic culture, which involves growing cells in a three-dimensional (3-D) environment as opposed to two-dimensional culture dishes. This 3D culture system is biochemically and physiologically more similar toin vivo tissue, but is technically challenging to maintain because of many factors (e.g. diffusion).[26]
There are different kinds of cell culture media which being used routinely in life science including the following:
| Component | Function |
|---|---|
| Carbon source (glucose/glutamine) | Source of energy |
| Amino acid | Building blocks of protein |
| Vitamins | Promote cell survival and growth |
| Balanced salt solution | Anisotonic mixture of ions to maintain optimumosmotic pressure within the cells and provide essential metal ions to act ascofactors for enzymatic reactions, cell adhesion etc. |
| Phenol red dye | pH indicator. The color of phenol red changes from orange/red at pH 7–7.4 to yellow at acidic (lower) pH and purple at basic (higher) pH. |
| Bicarbonate /HEPESbuffer | It is used to maintain a balanced pH in the media |
| Parameter | |
|---|---|
| Temperature | 37 °C |
| CO2 | 5% |
| Relative Humidity | 95% |
Cell line cross-contamination can be a problem for scientists working with cultured cells.[27] Studies suggest anywhere from 15 to 20% of the time, cells used in experiments have been misidentified or contaminated with another cell line.[28][29][30] Problems with cell line cross-contamination have even been detected in lines from theNCI-60 panel, which are used routinely for drug-screening studies.[31][32] Major cell line repositories, including theAmerican Type Culture Collection (ATCC), the European Collection of Cell Cultures (ECACC) and the German Collection of Microorganisms and Cell Cultures (DSMZ), have received cell line submissions from researchers that were misidentified by them.[31][33] Such contamination poses a problem for the quality of research produced using cell culture lines, and the major repositories are now authenticating all cell line submissions.[34] ATCC usesshort tandem repeat (STR)DNA fingerprinting to authenticate its cell lines.[35]
To address this problem of cell line cross-contamination, researchers are encouraged to authenticate their cell lines at an early passage to establish the identity of the cell line. Authentication should be repeated before freezing cell line stocks, every two months during active culturing and before any publication of research data generated using the cell lines. Many methods are used to identify cell lines, includingisoenzyme analysis,human lymphocyte antigen (HLA) typing, chromosomal analysis, karyotyping, morphology andSTR analysis.[35]
One significant cell-line cross contaminant is the immortalHeLa cell line. HeLa contamination was first noted in the early 1960s in non-human culture in the USA. Intraspecies contamination was discovered in nineteen cell lines in the seventies. In 1974, five human cell lines from the Soviet Union were found to be HeLa. A follow-up study analysing 50-odd cell lines indicated that half had HeLa markers, but contaminant HeLa had hybridised with the original cell lines. HeLa cell contamination fromair droplets has been reported. HeLa was even unknowingly injected into human subjects byJonas Salk in a 1978 vaccine trial.[36]
As cells generally continue to divide in culture, they generally grow to fill the available area or volume. This can generate several issues:
The choice ofculture medium might affect thephysiological relevance of findings from cell culture experiments due to the differences in the nutrient composition and concentrations.[38] A systematic bias in generated datasets was recently shown forCRISPR andRNAigene silencing screens,[39] and for metabolic profiling of cancercell lines.[38] Using agrowth medium that better represents the physiological levels of nutrients can improve the physiological relevance ofin vitro studies and recently such media types, as Plasmax[40] and Human Plasma Like Medium (HPLM),[41] were developed.
Among the common manipulations carried out on culture cells are media changes, passaging cells, and transfecting cells.These are generally performed using tissue culture methods that rely onaseptic technique. Aseptic technique aims to avoid contamination with bacteria, yeast, or other cell lines. Manipulations are typically carried out in abiosafety cabinet orlaminar flow cabinet to exclude contaminating micro-organisms.Antibiotics (e.g.penicillin andstreptomycin) and antifungals (e.g.amphotericin B andAntibiotic-Antimycotic solution) can also be added to the growth media.
As cells undergo metabolic processes, acid is produced and the pH decreases. Often, apH indicator is added to the medium to measure nutrient depletion.
In the case of adherent cultures, the media can be removed directly by aspiration, and then is replaced. Media changes in non-adherent cultures involve centrifuging the culture and resuspending the cells in fresh media.
Passaging (also known as subculture or splitting cells) involves transferring a small number of cells into a new vessel. Cells can be cultured for a longer time if they are split regularly, as it avoids the senescence associated with prolonged high cell density. Suspension cultures are easily passaged with a small amount of culture containing a few cells diluted in a larger volume of fresh media. For adherent cultures, cells first need to be detached; this is commonly done with a mixture oftrypsin-EDTA; however, other enzyme mixes are now available for this purpose. A small number of detached cells can then be used to seed a new culture. Some cell cultures, such asRAW cells are mechanically scraped from the surface of their vessel with rubber scrapers.
Another common method for manipulating cells involves the introduction of foreign DNA bytransfection. This is often performed to cause cells toexpress a gene of interest. More recently, the transfection ofRNAi constructs have been realized as a convenient mechanism for suppressing the expression of a particular gene/protein. DNA can also be inserted into cells using viruses, in methods referred to astransduction,infection ortransformation. Viruses, as parasitic agents, are well suited to introducing DNA into cells, as this is a part of their normal course of reproduction.
Cell lines that originate with humans have been somewhat controversial inbioethics, as they may outlive their parent organism and later be used in the discovery of lucrative medical treatments. In the pioneering decision in this area, theSupreme Court of California held inMoore v. Regents of the University of California that human patients have no property rights in cell lines derived from organs removed with their consent.[42]
It is possible to fuse normal cells with animmortalised cell line. This method is used to producemonoclonal antibodies. In brief, lymphocytes isolated from thespleen (or possibly blood) of animmunised animal are combined with an immortal myeloma cell line (B cell lineage) to produce ahybridoma which has the antibody specificity of the primary lymphocyte and the immortality of the myeloma.Selective growth medium (HA or HAT) is used to select against unfused myeloma cells; primary lymphoctyes die quickly in culture and only the fused cells survive. These are screened for production of the required antibody, generally in pools to start with and then after single cloning.
A cell strain is derived either from a primary culture or a cell line by the selection or cloning of cells having specific properties or characteristics which must be defined. Cell strains are cells that have been adapted to culture but, unlike cell lines, have a finite division potential. Non-immortalized cells stop dividing after 40 to 60 population doublings[43] and, after this, they lose their ability to proliferate (a genetically determined event known as senescence).[44]
Mass culture of animal cell lines is fundamental to the manufacture of viralvaccines and other products of biotechnology. Culture of humanstem cells is used to expand the number of cells and differentiate the cells into various somatic cell types for transplantation.[45] Stem cell culture is also used to harvest the molecules and exosomes that the stem cells release for the purposes of therapeutic development.[46]
Biological products produced byrecombinant DNA (rDNA) technology in animal cell cultures includeenzymes, synthetichormones, immunobiologicals (monoclonal antibodies,interleukins,lymphokines), andanticancer agents. Although many simpler proteins can be produced using rDNA in bacterial cultures, more complex proteins that areglycosylated (carbohydrate-modified) currently must be made in animal cells. Mammalian cells ensure expressed proteins are folded correctly and possess human-like glycosylation and post-translational modifications.[47] An important example of such a complex protein is the hormoneerythropoietin. The cost of growing mammalian cell cultures is high, so research is underway to produce such complex proteins in insect cells or in higher plants, use of single embryonic cell andsomatic embryos as a source for direct gene transfer via particle bombardment, transitgene expression andconfocal microscopy observation is one of its applications. It also offers to confirm single cell origin of somatic embryos and the asymmetry of the first cell division, which starts the process.
Cell culture is also a key technique forcellular agriculture, which aims to provide both new products and new ways of producing existing agricultural products like milk,(cultured) meat, fragrances, and rhino horn from cells and microorganisms. It is therefore considered one means of achievinganimal-free agriculture. It is also a central tool for teaching cell biology.[48]
Research intissue engineering,stem cells andmolecular biology primarily involves cultures of cells on flat plastic dishes. This technique is known as two-dimensional (2D) cell culture, and was first developed byWilhelm Roux who, in 1885, removed a portion of the medullary plate of an embryonic chicken and maintained it in warm saline for several days on a flat glass plate. From the advance ofpolymer technology arose today's standard plastic dish for 2D cell culture, commonly known as thePetri dish.Julius Richard Petri, a Germanbacteriologist, is generally credited with this invention while working as an assistant toRobert Koch. Various researchers today also utilize culturinglaboratory flasks, conicals, and even disposable bags like those used insingle-use bioreactors.
Aside from Petri dishes, scientists have long been growing cells within biologically derived matrices such as collagen or fibrin, and more recently, on synthetic hydrogels such as polyacrylamide or PEG. They do this in order to elicit phenotypes that are not expressed on conventionally rigid substrates. There is growing interest in controllingmatrix stiffness,[49] a concept that has led to discoveries in fields such as:
Cell culture in three dimensions has been touted as "Biology's New Dimension".[64] At present, the practice of cell culture remains based on varying combinations of single or multiple cell structures in 2D.[65] Currently, there is an increase in use of 3D cell cultures in research areas includingdrug discovery, cancer biology,regenerative medicine,nanomaterials assessment and basiclife science research.[66][67][68] 3D cell cultures can be grown using a scaffold or matrix, or in a scaffold-free manner. Scaffold based cultures utilize an acellular 3D matrix or a liquid matrix. Scaffold-free methods are normally generated in suspensions.[69] There are a variety of platforms used to facilitate the growth of three-dimensional cellular structures including scaffold systems such as hydrogel matrices[70] and solid scaffolds, and scaffold-free systems such as low-adhesion plates,nanoparticle facilitated magnetic levitation,[71] hanging drop plates,[72][73] androtary cell culture. Culturing cells in 3D leads to wide variation in gene expression signatures and partly mimics tissues in the physiological states.[74] A 3D cell culture model showed cell growth similar to that of in vivo than did a monolayer culture, and all three cultures were capable of sustaining cell growth.[75] As 3D culturing has been developed it turns out to have a great potential to design tumors models and investigate malignant transformation and metastasis, 3D cultures can provide aggerate tool for understanding changes, interactions, and cellular signaling.[76]
Eric Simon, in a 1988 NIH SBIR grant report, showed that electrospinning could be used to produce nano- and submicron-scale polystyrene and polycarbonate fibrous scaffolds specifically intended for use asin vitro cell substrates. This early use of electrospun fibrous lattices for cell culture and tissue engineering showed that various cell types including Human Foreskin Fibroblasts (HFF), transformed Human Carcinoma (HEp-2), and Mink Lung Epithelium (MLE) would adhere to and proliferate upon polycarbonate fibers. It was noted that, as opposed to the flattened morphology typically seen in 2D culture, cells grown on the electrospun fibers exhibited a more histotypic rounded 3-dimensional morphology generally observedin vivo.[17]
As the naturalextracellular matrix (ECM) is important in the survival, proliferation, differentiation and migration of cells, different hydrogel culture matrices mimicking natural ECM structure are seen as potential approaches to in vivo–like cell culturing.[77] Hydrogels are composed of interconnected pores with high water retention, which enables efficient transport of substances such as nutrients and gases. Several different types of hydrogels from natural and synthetic materials are available for 3D cell culture, including animal ECM extract hydrogels, protein hydrogels, peptide hydrogels, polymer hydrogels, andwood-based nanocellulose hydrogel.
The3D Cell Culturing by Magnetic Levitation method (MLM) is the application of growing 3D tissue by inducing cells treated with magnetic nanoparticle assemblies in spatially varying magnetic fields using neodymium magnetic drivers and promoting cell to cell interactions by levitating the cells up to the air/liquid interface of a standard petri dish. The magnetic nanoparticle assemblies consist of magnetic iron oxide nanoparticles, gold nanoparticles, and the polymer polylysine.3D cell culturing is scalable, with the capability for culturing 500 cells to millions of cells or from single dish to high-throughput low volume systems.
Cell culture is a fundamental component oftissue culture andtissue engineering, as it establishes the basics of growing and maintaining cellsin vitro.The major application of human cell culture is in stem cell industry, wheremesenchymal stem cells can be cultured and cryopreserved for future use. Tissue engineering potentially offers dramatic improvements in low cost medical care for hundreds of thousands of patients annually.
Vaccines forpolio,measles,mumps,rubella, andchickenpox are currently made in cell cultures. Due to theH5N1pandemic threat, research into using cell culture forinfluenza vaccines is being funded by theUnited States government. Novel ideas in the field includerecombinant DNA-based vaccines, such as one made using humanadenovirus (a common cold virus) as a vector,[78][79]and novel adjuvants.[80]
The technique of co-culturing is used to study cell crosstalk between two or more types of cells on a plate or in a 3D matrix. The cultivation of different stem cells and the interaction of immune cells can be investigated in an in vitro model similar to biological tissue. Since most tissues contain more than one type of cell, it is important to evaluate their interaction in a 3D culture environment to gain a better understanding of their interaction and to introduce mimetic tissues. There are two types of co-culturing: direct and indirect. While direct interaction involves cells being in direct contact with each other in the same culture media or matrix, indirect interaction involves different environments, allowing signaling and soluble factors to participate.[15][81]
Cell differentiation in tissue models during interaction between cells can be studied using the Co-Cultured System to simulate cancer tumors, to assess the effect of drugs on therapeutic trials, and to study the effect of drugs on therapeutic trials. The co-culture system in 3D models can predict the response to chemotherapy and endocrine therapy if the microenvironment defines biological tissue for the cells.
A co-culture method is used in tissue engineering to generate tissue formation with multiple cells interacting directly.[82]
Microfluidics technique is developed systems that can perform a process in a flow which are usually in a scale of micron. Microfluidics chip are also known as Lab-on-a-chip and they are able to have continuous procedure and reaction steps with spare amount of reactants and space. Such systems enable the identification and isolation of individual cells and molecules when combined with appropriate biological assays and high-sensitivity detection techniques.[83][84]
OoC systems mimic and control the microenvironment of the cells by growing tissues in microfluidics. Combining tissue engineering, biomaterials fabrication, and cell biology, it offers the possibility of establishing a biomimetic model for studying human diseases in the laboratory. In recent years, 3D cell culture science has made significant progress, leading to the development of OoC. OoC is considered as a preclinical step that benefits pharmaceutical studies,drug development and disease modeling.[85][86] OoC is an important technology that can bridge the gap between animal testing and clinical studies and also by the advances that the science has achieved could be a replace for in vivo studies for drug delivery and pathophysiological studies.[87]
Besides the culture of well-established immortalised cell lines, cells from primary explants of a plethora of organisms can be cultured for a limited period of time before senescence occurs (see Hayflick's limit). Cultured primary cells have been extensively used in research, as is the case of fish keratocytes in cell migration studies.[88][48][89]
Plant cell cultures are typically grown as cell suspension cultures in a liquid medium or ascallus cultures on a solid medium. The culturing of undifferentiated plant cells and calli requires the proper balance of the plant growth hormonesauxin andcytokinin.[citation needed]
Cells derived fromDrosophila melanogaster (most prominently,Schneider 2 cells) can be used for experiments which may be hard to do on live flies or larvae, such asbiochemical studies or studies usingsiRNA. Cell lines derived from the army wormSpodoptera frugiperda, includingSf9 andSf21, and from the cabbage looperTrichoplusia ni,High Five cells, are commonly used for expression of recombinant proteins usingbaculovirus.[90]
For bacteria and yeasts, small quantities of cells are usually grown on a solid support that contains nutrients embedded in it, usually a gel such as agar, while large-scale cultures are grown with the cells suspended in a nutrient broth.[citation needed]
The culture of viruses requires the culture of cells of mammalian, plant, fungal or bacterial origin as hosts for the growth and replication of the virus. Wholewild type viruses,recombinant viruses or viral products may be generated in cell types other than their natural hosts under the right conditions. Depending on the species of the virus, infection andviral replication may result in host cell lysis and formation of aviral plaque.[citation needed]
 |
| Cell line | Meaning | Organism | Origin tissue | Morphology | Links |
|---|---|---|---|---|---|
| 3T3-L1 | "3-day transfer, inoculum 3 x 10^5 cells" | Mouse | Embryo | Fibroblast | ECACCCellosaurus |
| 4T1 | Mouse | Mammary gland | ATCCCellosaurus | ||
| 1321N1 | Human | Brain | Astrocytoma | ECACCCellosaurus | |
| 9L | Rat | Brain | Glioblastoma | ECACCCellosaurus | |
| A172 | Human | Brain | Glioblastoma | ECACCCellosaurus | |
| A20 | Mouse | Blymphoma | Blymphocyte | Cellosaurus | |
| A253 | Human | Submandibular duct | Head and neck carcinoma | ATCCCellosaurus | |
| A2780 | Human | Ovary | Ovarian carcinoma | ECACCCellosaurus | |
| A2780ADR | Human | Ovary | Adriamycin-resistant derivative of A2780 | ECACCCellosaurus | |
| A2780cis | Human | Ovary | Cisplatin-resistant derivative of A2780 | ECACCCellosaurus | |
| A431 | Human | Skin epithelium | Squamous cell carcinoma | ECACCCellosaurus | |
| A549 | Human | Lung | Lung carcinoma | ECACCCellosaurus | |
| AB9 | Zebrafish | Fin | Fibroblast | ATCCCellosaurus | |
| AHL-1 | Armenian Hamster Lung-1 | Hamster | Lung | ECACCArchived 24 November 2021 at theWayback MachineCellosaurus | |
| ALC | Mouse | Bone marrow | Stroma | PMID 2435412[91]Cellosaurus | |
| B16 | Mouse | Melanoma | ECACCArchived 24 November 2021 at theWayback MachineCellosaurus | ||
| B35 | Rat | Neuroblastoma | ATCCCellosaurus | ||
| BCP-1 | Human | PBMC | HIV+ primary effusion lymphoma | ATCCCellosaurus | |
| BEAS-2B | Bronchial epithelium + Adenovirus 12-SV40 virus hybrid (Ad12SV40) | Human | Lung | Epithelial | ECACCCellosaurus |
| bEnd.3 | Brain Endothelial 3 | Mouse | Brain/cerebral cortex | Endothelium | Cellosaurus |
| BHK-21 | Baby Hamster Kidney-21 | Hamster | Kidney | Fibroblast | ECACCArchived 24 November 2021 at theWayback MachineCellosaurus |
| BOSC23 | Packaging cell line derived fromHEK 293 | Human | Kidney (embryonic) | Epithelium | Cellosaurus |
| BT-20 | Breast Tumor-20 | Human | Breast epithelium | Breast carcinoma | ATCCCellosaurus |
| BxPC-3 | Biopsy xenograft of Pancreatic Carcinoma line 3 | Human | Pancreatic adenocarcinoma | Epithelial | ECACCCellosaurus |
| C2C12 | Mouse | Myoblast | ECACCCellosaurus | ||
| C3H-10T1/2 | Mouse | Embryonic mesenchymal cell line | ECACCCellosaurus | ||
| C6 | Rat | Brainastrocyte | Glioma | ECACCCellosaurus | |
| C6/36 | Insect -Asian tiger mosquito | Larval tissue | ECACCCellosaurus | ||
| Caco-2 | Human | Colon | Colorectal carcinoma | ECACCCellosaurus | |
| Cal-27 | Human | Tongue | Squamous cell carcinoma | ATCCCellosaurus | |
| Calu-3 | Human | Lung | Adenocarcinoma | ATCCCellosaurus | |
| CGR8 | Mouse | Embryonic stem cells | ECACCCellosaurus | ||
| CHO | Chinese Hamster Ovary | Hamster | Ovary | Epithelium | ECACCArchived 29 October 2021 at theWayback MachineCellosaurus |
| CML T1 | Chronic myeloid leukemia T lymphocyte 1 | Human | CML acute phase | T cell leukemia | DSMZCellosaurus |
| CMT12 | Canine Mammary Tumor 12 | Dog | Mammary gland | Epithelium | Cellosaurus |
| COR-L23 | Human | Lung | Lung carcinoma | ECACCCellosaurus | |
| COR-L23/5010 | Human | Lung | Lung carcinoma | ECACCCellosaurus | |
| COR-L23/CPR | Human | Lung | Lung carcinoma | ECACCCellosaurus | |
| COR-L23/R23- | Human | Lung | Lung carcinoma | ECACCCellosaurus | |
| COS-7 | Cercopithecus aethiops, origin-defective SV-40 | Old World monkey -Cercopithecus aethiops (Chlorocebus) | Kidney | Fibroblast | ECACCCellosaurus |
| COV-434 | Human | Ovary | Ovarian granulosa cell carcinoma | PMID 8436435[92]ECACCCellosaurus | |
| CT26 | Mouse | Colon | Colorectal carcinoma | Cellosaurus | |
| D17 | Dog | Lung metastasis | Osteosarcoma | ATCCCellosaurus | |
| DAOY | Human | Brain | Medulloblastoma | ATCCCellosaurus | |
| DH82 | Dog | Histiocytosis | Monocyte/macrophage | ECACCCellosaurus | |
| DU145 | Human | Androgen insensitive prostate carcinoma | ATCCCellosaurus | ||
| DuCaP | Dura mater cancer of the Prostate | Human | Metastatic prostate carcinoma | Epithelial | PMID 11317521[93]Cellosaurus |
| E14Tg2a | Mouse | Embryonic stem cells | ECACCCellosaurus | ||
| EL4 | Mouse | T cell leukemia | ECACCCellosaurus | ||
| EM-2 | Human | CML blast crisis | Ph+ CML line | DSMZCellosaurus | |
| EM-3 | Human | CML blast crisis | Ph+ CML line | DSMZCellosaurus | |
| EMT6/AR1 | Mouse | Mammary gland | Epithelial-like | ECACCCellosaurus | |
| EMT6/AR10.0 | Mouse | Mammary gland | Epithelial-like | ECACCCellosaurus | |
| FM3 | Human | Lymph node metastasis | Melanoma | ECACCCellosaurus | |
| GL261 | Glioma 261 | Mouse | Brain | Glioma | Cellosaurus |
| H1299 | Human | Lung | Lung carcinoma | ATCCCellosaurus | |
| HaCaT | Human | Skin | Keratinocyte | CLSCellosaurus | |
| HCA2 | Human | Colon | Adenocarcinoma | ECACCCellosaurus | |
| HEK 293 | Human Embryonic Kidney 293 | Human | Kidney (embryonic) | Epithelium | ECACCCellosaurus |
| HEK 293T | HEK 293 derivative | Human | Kidney (embryonic) | Epithelium | ECACCCellosaurus |
| HeLa | "Henrietta Lacks" | Human | Cervix epithelium | Cervical carcinoma | ECACCCellosaurus |
| Hepa1c1c7 | Clone 7 of clone 1 hepatoma line 1 | Mouse | Hepatoma | Epithelial | ECACCCellosaurus |
| Hep G2 | Human | Liver | Hepatoblastoma | ECACCCellosaurus | |
| High Five | Insect (moth) -Trichoplusia ni | Ovary | Cellosaurus | ||
| HL-60 | Human Leukemia-60 | Human | Blood | Myeloblast | ECACCCellosaurus |
| HT-1080 | Human | Fibrosarcoma | ECACCCellosaurus | ||
| HT-29 | Human | Colon epithelium | Adenocarcinoma | ECACCCellosaurus | |
| J558L | Mouse | Myeloma | B lymphocyte cell | ECACCCellosaurus | |
| Jurkat | Human | White blood cells | T cellleukemia | ECACCCellosaurus | |
| JY | Human | Lymphoblastoid | EBV-transformed B cell | ECACCCellosaurus | |
| K562 | Human | Lymphoblastoid | CML blast crisis | ECACCCellosaurus | |
| KBM-7 | Human | Lymphoblastoid | CML blast crisis | Cellosaurus | |
| KCL-22 | Human | Lymphoblastoid | CML | DSMZCellosaurus | |
| KG1 | Human | Lymphoblastoid | AML | ECACCCellosaurus | |
| Ku812 | Human | Lymphoblastoid | Erythroleukemia | ECACCCellosaurus | |
| KYO-1 | Kyoto-1 | Human | Lymphoblastoid | CML | DSMZCellosaurus |
| L1210 | Mouse | Lymphocytic leukemia | Ascitic fluid | ECACCCellosaurus | |
| L243 | Mouse | Hybridoma | Secretes L243 mAb (against HLA-DR) | ATCCCellosaurus | |
| LNCaP | Lymph Node Cancer of the Prostate | Human | Prostatic adenocarcinoma | Epithelial | ECACCCellosaurus |
| MA-104 | Microbiological Associates-104 | African Green Monkey | Kidney | Epithelial | Cellosaurus |
| MA2.1 | Mouse | Hybridoma | Secretes MA2.1 mAb (against HLA-A2 and HLA-B17) | ATCCCellosaurus | |
| Ma-Mel 1, 2, 3....48 | Human | Skin | A range ofmelanoma cell lines | ECACCArchived 24 November 2021 at theWayback MachineCellosaurus | |
| MC-38 | Mouse Colon-38 | Mouse | Colon | Adenocarcinoma | Cellosaurus |
| MCF-7 | Michigan Cancer Foundation-7 | Human | Breast | Invasive breast ductal carcinoma ER+, PR+ | ECACCCellosaurus |
| MCF-10A | Michigan Cancer Foundation-10A | Human | Breast epithelium | ATCCCellosaurus | |
| MDA-MB-157 | M.D. Anderson - Metastatic Breast-157 | Human | Pleural effusion metastasis | Breast carcinoma | ECACCCellosaurus |
| MDA-MB-231 | M.D. Anderson - Metastatic Breast-231 | Human | Pleural effusion metastasis | Breast carcinoma | ECACCCellosaurus |
| MDA-MB-361 | M.D. Anderson - Metastatic Breast-361 | Human | Melanoma (contaminated by M14) | ECACCCellosaurus | |
| MDA-MB-468 | M.D. Anderson - Metastatic Breast-468 | Human | Pleural effusion metastasis | Breast carcinoma | ATCCCellosaurus |
| MDCK II | Madin Darby Canine Kidney II | Dog | Kidney | Epithelium | ECACCCellosaurus |
| MG63 | Human | Bone | Osteosarcoma | ECACCCellosaurus | |
| MIA PaCa-2 | Human | Prostate | Pancreatic Carcinoma | ATCCCellosaurus | |
| MOR/0.2R | Human | Lung | Lung carcinoma | ECACCCellosaurus | |
| Mono-Mac-6 | Human | White blood cells | Myeloid metaplasicAML | DSMZCellosaurus | |
| MRC-5 | Medical Research Council cell strain 5 | Human | Lung (fetal) | Fibroblast | ECACCArchived 24 November 2021 at theWayback MachineCellosaurus |
| MTD-1A | Mouse | Epithelium | Cellosaurus | ||
| MyEnd | Myocardial Endothelial | Mouse | Endothelium | Cellosaurus | |
| NCI-H69 | Human | Lung | Lung carcinoma | ECACCCellosaurus | |
| NCI-H69/CPR | Human | Lung | Lung carcinoma | ECACCCellosaurus | |
| NCI-H69/LX10 | Human | Lung | Lung carcinoma | ECACCCellosaurus | |
| NCI-H69/LX20 | Human | Lung | Lung carcinoma | ECACCCellosaurus | |
| NCI-H69/LX4 | Human | Lung | Lung carcinoma | ECACCCellosaurus | |
| Neuro-2a | Mouse | Nerve/neuroblastoma | Neuronal stem cells | ECACCCellosaurus | |
| NIH-3T3 | NIH, 3-day transfer, inoculum 3 x 105 cells | Mouse | Embryo | Fibroblast | ECACCCellosaurus |
| NALM-1 | Human | Peripheral blood | Blast-crisis CML | ATCCCellosaurus | |
| NK-92 | Human | Leukemia/lymphoma | ATCCCellosaurus | ||
| NTERA-2 | Human | Lung metastasis | Embryonal carcinoma | ECACCCellosaurus | |
| NW-145 | Human | Skin | Melanoma | ESTDABArchived 2011-11-16 at theWayback MachineCellosaurus | |
| OK | Opossum Kidney | Virginia opossum -Didelphis virginiana | Kidney | ECACCCellosaurus | |
| OPCN / OPCT cell lines | Human | Prostate | Range of prostate tumour lines | Cellosaurus | |
| P3X63Ag8 | Mouse | Myeloma | ECACCCellosaurus | ||
| PANC-1 | Human | Duct | Epithelioid Carcinoma | ATCCCellosaurus | |
| PC12 | Rat | Adrenal medulla | Pheochromocytoma | ECACCCellosaurus | |
| PC-3 | Prostate Cancer-3 | Human | Bone metastasis | Prostate carcinoma | ECACCCellosaurus |
| Peer | Human | T cell leukemia | DSMZCellosaurus | ||
| PNT1A | Human | Prostate | SV40-transformed tumour line | ECACCCellosaurus | |
| PNT2 | Human | Prostate | SV40-transformed tumour line | ECACCCellosaurus | |
| Pt K2 | The second cell line derived fromPotorous tridactylis | Long-nosed potoroo -Potorous tridactylus | Kidney | Epithelial | ECACCCellosaurus |
| Raji | Human | Blymphoma | Lymphoblast-like | ECACCCellosaurus | |
| RBL-1 | Rat Basophilic Leukemia-1 | Rat | Leukemia | Basophil cell | ECACCCellosaurus |
| RenCa | Renal Carcinoma | Mouse | Kidney | Renal carcinoma | ATCCCellosaurus |
| RIN-5F | Mouse | Pancreas | ECACCCellosaurus | ||
| RMA-S | Mouse | T cell tumour | Cellosaurus | ||
| S2 | Schneider 2 | Insect -Drosophila melanogaster | Late stage (20–24 hours old) embryos | ATCCCellosaurus | |
| SaOS-2 | Sarcoma OSteogenic-2 | Human | Bone | Osteosarcoma | ECACCCellosaurus |
| Sf21 | Spodoptera frugiperda 21 | Insect (moth) -Spodoptera frugiperda | Ovary | ECACCCellosaurus | |
| Sf9 | Spodoptera frugiperda 9 | Insect (moth) -Spodoptera frugiperda | Ovary | ECACCCellosaurus | |
| SH-SY5Y | Human | Bone marrow metastasis | Neuroblastoma | ECACCCellosaurus | |
| SiHa | Human | Cervix epithelium | Cervical carcinoma | ATCCCellosaurus | |
| SK-BR-3 | Sloan-Kettering Breast cancer 3 | Human | Breast | Breast carcinoma | DSMZCellosaurus |
| SK-OV-3 | Sloan-Kettering Ovarian cancer 3 | Human | Ovary | Ovarian carcinoma | ECACCCellosaurus |
| SK-N-SH | Human | Brain | Epithelial | ATCCCellosaurus | |
| T2 | Human | T cell leukemia/B cell linehybridoma | ATCCCellosaurus | ||
| T-47D | Human | Breast | Breast ductal carcinoma | ECACCCellosaurus | |
| T84 | Human | Lung metastasis | Colorectal carcinoma | ECACCCellosaurus | |
| T98G | Human | Glioblastoma-astrocytoma | Epithelium | ECACCCellosaurus | |
| THP-1 | Human | Monocyte | Acute monocytic leukemia | ECACCCellosaurus | |
| U2OS | Human | Osteosarcoma | Epithelial | ECACCCellosaurus | |
| U373 | Human | Glioblastoma-astrocytoma | Epithelium | ECACCArchived 24 November 2021 at theWayback MachineCellosaurus | |
| U87 | Human | Glioblastoma-astrocytoma | Epithelial-like | ECACCCellosaurus | |
| U937 | Human | Leukemic monocytic lymphoma | ECACCCellosaurus | ||
| VCaP | Vertebral Cancer of the Prostate | Human | Vertebra metastasis | Prostate carcinoma | ECACCCellosaurus |
| Vero | From Esperanto:verda (green, for green monkey)reno (kidney) | African green monkey -Chlorocebus sabaeus | Kidney epithelium | ECACCCellosaurus | |
| VG-1 | Human | Primary effusion lymphoma | Cellosaurus | ||
| WM39 | Human | Skin | Melanoma | ESTDABCellosaurus | |
| WT-49 | Human | Lymphoblastoid | ECACCCellosaurus | ||
| YAC-1 | Mouse | Lymphoma | ECACCCellosaurus | ||
| YAR | Human | Lymphoblastoid | EBV-transformed B cell | Human Immunology[94]ECACCCellosaurus |
| History |  | ||||
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| General concepts | |||||
| Basic techniques and tools |
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| Applications | |||||
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| Overview |
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| Engineering |
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