Аннотация
Recent studies indicate that polymer-encapsulated PC12 cells release
sufficient amounts of dopamine to significantly alter behavioural
paradigms in animals with unilateral lesions of dopaminergic midbrain
neurons. Because cell fine structure provides a useful measure for
assessment of storage function, exocytosis, metabolism, cell activity
and cell viability, we examined the ultrastructure of PC12 cells
grown in semi-permeable polymer capsules maintained in vitro or implanted
into the forebrain of rats or guinea pigs. Encapsulated PC12 cells
remained viable and continued to divide for the entire evaluation
period of six months. Overall morphologies of encapsulated PC12 cells
were similar in both environments and they resembled PC12 cells grown
in monolayer cultures. In short-term cultures, encapsulated PC12
cells typically contained abundant quantities of chromaffin cell-like
granules. The encapsulated cells had initially abundant microvilli
on their surfaces which decline in frequency over time. After long-term
enclosure for ten weeks or more, fewer secretory granules were detected
in the cytoplasm of cells in capsules cultured in vitro and in brain-implanted
capsules. Some cells in implanted capsules had long slender filipodia
that were not present on PC12 cells in cultured capsules. The morphological
changes of PC12 cells may correlate with altered growth conditions
such as serum and oxygen concentrations, the presence or absence
of growth factors in different environments, and with changes of
cell interactions related to cell densities and build up of debris
within the capsules over time. Since dopaminergic PC12 pheochromocytoma
cells remain viable in semi-permeable polymer capsules for at least
six months, such 'cell-capsules' could provide an alternative to
dopamine-secreting embryonic neural grafts in dopamine replacement
therapies.
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