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E . N. W I L L M E R
X . T I S S U E C U L T U R E A N D T H E M E A N I N G OF
D I F F E R E N T I A T I O N
In making hanging-drop cultures and the like, there has generally
been a tendency to encourage growth by cell multiplication, and this,
in itself is inimical to cell differentiation; it is thus not surprising to find
as Parker (1936) did, that after long-continued cultivation in plasma
alone, with suitable patching and refreshing of the medium with
heparin plasma or with serum, the cells would, after a time, differentiate; but, when they did so, they often assumed a great variety of forms,
some of which did not seem to correspond very closely to any of the
probable original forms in vivo. On the other hand, prolonged culture
sions, clones and pure lines, further changes tend to occur and in many
cases become irreversible. Such cells can then be aptly described as
"tissue culture cells", of liver origin, connective tissue origin etc.
The relationship between "tissue culture cells" and malignant cells is
also an intriguing one. Cells in Tissue Culture sometimes seem to acquire properties of malignancy, but they do not necessarily do so, and
malignant cells may lose their malignancy after culture in vitro.
One curious feature of pure strains of cells is that at any one time
there often, if not always, appear to be two morphological classes of
cells in them, the spherical or somewhat spindle-shaped type on the one
hand and the extended, flattened type on the other (Figs. 6 and 7).
It would be interesting to know whether these are like the two states
of the lymphocytes, the active polarized and the stagnant and unpolarized,
or the "active" and "resting" forms of macrophages (Jacoby, 1938)
or are the expression of more permanent differences. Also it would be
nice to know if the two forms could be compared with the two possible
forms of mesenchyme cell suggested above and which might therefore
be working more or less in mutual opposition and thus helping to
stabilize the most suitable conditions for the colony as a whole.
If this were the correct interpretation, the form and activity of the
cell at any one moment could perhaps, as in JVaegleria, be open to
modification, and this time by the actions of the other cells in the immediate vicinity producing local environmental conditions. Such local
conditions v/ould presumably change from time to time and thus the
form of the cells might also have to change in response. Cells extracting
substances from their surroundings may be creating shortages for their
neighbours, while others producing by-products may be creating
excesses for their neighbours.
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