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Cultured Cells and Cell Lines - The cultured cells may be of 'the following three types:

(i) Precursor or stem cells (master cells)" which are capable of proliferation, but remain undifferentiated until the correct inducing conditions are applied so that some or all of the cells mature to differentiated cells; these are totipotent or pluripotent (or multi potent) cells (capable of differentiating into various kinds of cells). Stem cells differ in sternness. For instance, totipotent stem cells can give rise to entire blood producing, and immune" systems; they differ from pluripotent stem cells, which are less general, but can still differentiate into several types.

(ii) Undifferentiated, but committed precursor cells.

(iii) Mature differentiated cells. It may be useful to think of a cell culture as being in equilibrium between multipotent stem cells, undifferentiated but committed precursor cells and mature differentiated cells.

This equilibrium may shift according to the environmental condition. Following are some of the examples:

(i) High serum, growth factors, low cell density (i.e. routine serial passage) will promote cell proliferation.

(ii) Low serum, appropriate hormones and high cell density will promote differentiation.

The source of the culture will also determine which of the above three types of cells will be present in the culture. Following are some examples:

(i) Cell lines derived from the embryo may contain more stem cells (or precursor cells), which will be capable of greater self renewal than the cultures from adults.

(ii) The cultures from tissues, which are undergoing continuous renewal in vivo (e.g. epidermis, intestinal epithelium, hemopoietic cells) will still contain stem cells, even though they are derived from adults. These may survive indefinitely.

(iii) Cultures from tissues, which renew only under stress (fibroblasts, muscle, glia), may only contain committed precursor cells with a limited culture life span. From any of the three kinds of cells derived from a primary explant, cell lines may be developed.

After the first subculture, the primary culture becomes, a cell line and may be propagated and subcultured several times with each successive subculture, the component of the population with the ability to proliferate most rapidly will gradually predominate and non proliferating or slowly proliferating cells will be diluted out. Although some selection and phenotypic drift will continue, by the third passage the culture becomes more stable and is characterized by rapidly proliferating cells.

The cell lines, as above, may be propagated in an unaltered form for a limited number of cell generations, beyond which they may either die out or give rise to continuous cell lines. The continuous cell lines are often aneuploid and have larger variation in chromosome number, while the finite cell lines are often euploid, with little variation, if any in the chromosome numbers. The alteration in a culture giving rise to a continuous cell line is commonly called in vitro transformation, which may be spontaneous or chemically or virally (Epstein Barr Virus) induced.

The term 'transformation' has been applied to the process of formation of a continuous cell line, not only because the culture undergoes morphological and kinetic alterations, but: also because the formation of a continuous cell line is often accompanied by an increase in tumorigenicity exhibiting the following properties of malignant transformations:

(i) reduced serum requirement,

(ii) reduced density,

(iii) limitation of growth,

(iv) growth in semisolid media and

(v) aneuploidy.