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which eventually proves toxic. It may be relevant that Cohen and Eagle
(1961) found that the growth of cells in continuous culture in a chemostat was eventually slowed down by accumulation of some nondialysable inhibitory substance at present unidentified. Second, if
respiration slowly declines in vitro, and there is good evidence that it
does, then on the theory of Longmuir and Bourke (see preceding
section) this would lead to a failure of intracellular oxygen transport,
with consequent central necrosis.
T o sum up, the relatively short survival time of mature organs in
vitro can most likely be ascribed to a failure of respiration. This failure
may well be accelerated by the leaching out of necessary metabolites,
coenzymes etc. or by the accumulation of toxic materials, but its
primary cause must be the dissociation of the organ from the rest of
the body. The rather rapid mortality of fully differentiated cells in
both tissue and organ culture, compared with the apparent immortality of undifferentiated cells is a fact which must be faced, and one
which exposes our ignorance of the factors which maintain cell life
in vivo. The culture of embryonic organs has emphasized their remarkable autonomy. The culture of mature organs has shown rather the
reverse and pointed to the existence within the adult animal of influences
at present unidentified. Perhaps this is the most significant contribution
that the method has yet made. Further advances in organ culture
technique would seem to depend on the discovery of some of these
in vivo mechanisms. T w o factors which may be suggested are the circulating white blood cells which may have either a nutritive or a scavenging function (? removal of non-diffusible waste products) and the autonomic nerve supply which may have a trophic function. Doubtless
there are many others and they may not all be chemical, or even
material. This is one of the most fundamental problems in physiology
and the organ-culture method is well-placed to assist in its solution.
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