Applications of cell culture
Cell culture is one of the major tools used in cellular and molecular biology, providing excellent model systems for studying the normal physiology and biochemistry of cells (e.g., metabolic studies, aging), the effects of drugs and toxic compounds on the cells, and mutagenesis and carcinogenesis. It is also used in drug screening and development, and large scale manufacturing of biological compounds (e.g., vaccines, therapeutic proteins). The major advantage of using cell culture for any of these applications is the consistency and reproducibility of results that can be obtained from using a batch of clonal cells.
Cell cultures provide a good model system for studying 1) basic cell biology and biochemistry, 2) the interactions between disease-causing agents and cells, 3) the effects of drugs on cells, 4) the process and triggers for aging, and 5) nutritional studies.
Cultured cells are widely used alone or in conjunction with animal tests to study the effects of new drugs, cosmetics and chemicalson survival and growth in a wide variety of cell types. Especially important are liver-and kidney-derived cell cultures.
Since both normal cells and cancer cells can be grown in culture, the basic differences between them can be closely studied. In addition, it is possible, by the use of chemicals, viruses and radiation, to convert normal cultured cells to cancer causing cells. Thus, the mechanisms that cause the change can be studied. Cultured cancer cells also serve as a test system to determine suitable drugs and methods for selectively destroying types of cancer.
One of the earliest and major uses of cell culture is the replication of viruses in cell cultures (in place of animals) for use in vaccine production. Cell cultures are also widely used in the clinical detection and isolation of viruses, as well as basic research into how they grow and infect organisms.
While cultured cells can be used to produce many important produces, three areas have generating the most interest. First is the large-scale production of viruses for use in vaccine production. These include vaccines for polio, rabies, chicken pox, hepatitis B and measles. Second, is the large scale production of cells that have been geneticallyengineered to produce proteins that have medicinal or commercial value. These include monoclonal antibodies, insulin, hormones, etc. Third, is the use of cells as replacement tissues and organs. Artificial skinfor use in treating burns and ulcers is the first commercially available product. However, testing is underway on artificial organs such as pancreas, liver and kidney. A potential supply of replacement cells and tissues may come out of work currently being done with both embryonic and adult stem cells. These are cells that have the potential todifferentiate into a variety of different cells types. It is hoped that learning how to control the development of these cells may offer new treatment approaches for a wide variety of medical conditions.
Amniocentesis, a diagnostic technique that enables doctors to remove and culture fetal cells from pregnant women, has given doctors an important tool for the early diagnosis of fetal disorders. These cells can then be examined for abnormalities in their chromosomes and genes using karyotyping, chromosome painting and other molecular techniques.
The ability to transfect or reprogram cultured cells with new genetic material (DNA and genes) has provided a major tool to molecular biologists wishing to study the cellular effects of the expression of theses genes (new proteins). These techniques can also be used to produce these new proteins in large quantity in cultured cells for further study. Insect cells are widely used as miniature cells factories to express substantial quantities of proteins that they manufacture after being infected with genetically engineered baculoviruses.
The ability to genetically engineer cells has also led to their use for gene therapy. Cells can be removed from a patient lacking a functional gene and the missing or damaged gene can then be replaced. The cells can be grown for a while in culture and then replaced into the patient. An alternative approach is to place the missing gene into a viral vector and then “infect” the patient with the virus in the hope that the missing gene will then be expressed in the patient’s cells.
Cell-based assays have become increasingly important for the pharmaceutical industry, not just for cytotoxicity testing but also for highthroughput screening of compounds that may have potential use as drugs. Originally, these cell culture tests were done in 96 well plates, but increasing use is now being made of 384 and 1536 well plates.