In order to clarify the contraversial structure that CAJAL (1889, 1893, 1911) called “interstitial cells” in the intestine, we have compared the descriptions by CAJAL with our recent findings.
CAJAL defined three groups of interstitial cells in the intestine: those in the mucosa, the deep muscular plexus, and the myenteric plexus. In the deep muscular plexus, he described cells with small perikarya and long, branching processes. Neither glial cells nor ZIO positive fibroblast-like cells, the only cell types seen in the numbers and location necessary to support CAJAL's observations, conformed with the morphology he described. CAJAL might have described a composite cell, or chimera, the cell body being that of a glial (or perhaps a fibroblast-like) cell and the processes being simultaneously stained neurites that ran in close association with the cell.
In the myenteric plexus, staining with S-100 protein for glial cells and ZIO for fibroblast-like cells reveal cells between the external muscle layers. Cells stained with S-100 protein resemble the drawings and also his description of the interstitial cells, although these cells appear to be less frequent than CAJAL's drawings indicate. There are numerous glial cells in the ganglia and primary strands of the plexus which were not included in CAJAL's publications. Conversely, the fibroblast-like cells are incidentally associated with nerve fibers. Although they lie in the same plane, the fibroblast-like cells form a pattern distinct from that of the nerve fibers of the tertiary component of the myenteric plexus. These cells occur in the distribution and numbers of the interstitial cells described by CAJAL. They are stained by ZIO and also immunoreactive for gamma-aminobutyric acid. They can be identified by scanning electron microscopy.
In the mucosa, Golgi staining reveals a pattern of nerve fiber bundles that is indistinguishable from CAJAL's drawings. Glial cell bodies frequently occur at the intersections of these bundles and appear as cell nuclei surrounded by a cytoplasm which is actually the stained nerve fiber bundles. What CAJAL depicted as interstitial cells were composite structures consisting of glial cells and contiguous nerve fiber bundles.
We conclude that the structures which CAJAL called interstitial cells in the intestine do not originate from one cell type. Nevertheless, two groups of fibroblast-like cells, those lying parallel and close to the nerve strands of the deep muscular plexus and those of the myenteric plexus, can be recognized by ZIO staining and scanning electron microscopy. These should be called interstitial cells in conformity with general usage and the numbering system adopted by THUNEBERG (1982), i. e., ICC-I for those at the level of the myenteric plexus, and ICC-III for those associated with the deep muscular plexus.