14. CELL A G G R E G A T E S
519
I V . R E M A R K S ON T H E I N T E R N A L P A T T E R N S
OF A G G R E G A T E S
The restitution of organized aggregates from free cells can be subdivided, for convenience, into three phases: (1) the initial clumping of
cells into randomly constructed clusters or primary aggregates. In these,
the cells are held together without noticeable histological order, interspersed arbitrarily and regardless of type or origin; this applies to all
aggregates, whether obtained by self-aggregation or compounded by
rotation. In their early stages, primary aggregates can be readily
redispersed by flushing through a fine pipette. Intercellular distances
between the clustered cells may be well above the 100-200A considered
"typical" for cohering cells, nevertheless the cells are held together in a
manner conducive to histotypic organization. Explanations of such
primary, non-selective cell attachment should account for the nature of
this distance-binding and the subsequent tightening up of cell contacts.
In this context it is important that cells, thus linked, are readily capable
of moving relative to each other; their shifts and migrations are
characteristic of this transitory association and are, presumably,
essential for assortment of the cells into more stable systems. (2) In
secondary aggregates, generally 24-36 h after dissociation, the cells are
mostly arranged in histologically identifiable groupings comprising
functionally matching cells. Cell mobility is gradually reduced as
structural stabilization sets in. Cell divisions, usually arrested at dissociation, reappear, their time of onset varying in different kinds of
cells and with nutritional conditions. The initial pattern within the
aggregates becomes thus increasingly complicated by cell proliferation,
differential growth, etc. (3) In tertiary aggregates, histodifferentiation and
growth continue; under suitable conditions of cultivation, development
may proceed beyond the stage achieved by the tissue of origin at the
time of dissociation. Most aggregates of embryonic cells will have
reached the third stage in 36 h. However, the time factors involved in
all three stages vary with the kind of cell, with the combination of cells,
the pretreatment of the cells, and the conditions of their culture.
Needless to say, these stages overlap and may not apply uniformly even
throughout the same aggregate, particularly when it is of heterotypic
composition.
The difference in cell-binding mechanisms between primary and
later aggregates, particularly with reference to the transition from nonselective to histotypic cell contact, is a wide-open question. Quite
obviously, non-selective binding does not represent in this case the sort
of clumping that cells show in the presence of basic polymers or basic
519
I V . R E M A R K S ON T H E I N T E R N A L P A T T E R N S
OF A G G R E G A T E S
The restitution of organized aggregates from free cells can be subdivided, for convenience, into three phases: (1) the initial clumping of
cells into randomly constructed clusters or primary aggregates. In these,
the cells are held together without noticeable histological order, interspersed arbitrarily and regardless of type or origin; this applies to all
aggregates, whether obtained by self-aggregation or compounded by
rotation. In their early stages, primary aggregates can be readily
redispersed by flushing through a fine pipette. Intercellular distances
between the clustered cells may be well above the 100-200A considered
"typical" for cohering cells, nevertheless the cells are held together in a
manner conducive to histotypic organization. Explanations of such
primary, non-selective cell attachment should account for the nature of
this distance-binding and the subsequent tightening up of cell contacts.
In this context it is important that cells, thus linked, are readily capable
of moving relative to each other; their shifts and migrations are
characteristic of this transitory association and are, presumably,
essential for assortment of the cells into more stable systems. (2) In
secondary aggregates, generally 24-36 h after dissociation, the cells are
mostly arranged in histologically identifiable groupings comprising
functionally matching cells. Cell mobility is gradually reduced as
structural stabilization sets in. Cell divisions, usually arrested at dissociation, reappear, their time of onset varying in different kinds of
cells and with nutritional conditions. The initial pattern within the
aggregates becomes thus increasingly complicated by cell proliferation,
differential growth, etc. (3) In tertiary aggregates, histodifferentiation and
growth continue; under suitable conditions of cultivation, development
may proceed beyond the stage achieved by the tissue of origin at the
time of dissociation. Most aggregates of embryonic cells will have
reached the third stage in 36 h. However, the time factors involved in
all three stages vary with the kind of cell, with the combination of cells,
the pretreatment of the cells, and the conditions of their culture.
Needless to say, these stages overlap and may not apply uniformly even
throughout the same aggregate, particularly when it is of heterotypic
composition.
The difference in cell-binding mechanisms between primary and
later aggregates, particularly with reference to the transition from nonselective to histotypic cell contact, is a wide-open question. Quite
obviously, non-selective binding does not represent in this case the sort
of clumping that cells show in the presence of basic polymers or basic