Stromal cells in the human gut show ultrastructural features of fibroblasts and smooth muscle cells but not myofibroblasts

Abstract

The free spindled cells of the lamina propria of the gut have been reported as showing fibroblastic, smooth-muscle and myofibroblastic differentiation. A precise understanding of the differentiation of these cells is essential for appreciating their functions, and this paper addresses this question using ultrastructural analysis. Histologically normal samples from different areas of the gastrointestinal tract were studied. Both subepithelial stromal cells, lying immediately beneath the basal lamina, and the deeper interstitial stromal cells, were studied. Subepithelial and interstitial cells had comparable features, reinforcing the idea that these formed a single reticulum of cells. Two major cell types were identified. Some were smooth-muscle cells, on the basis of abundant myofilaments with focal densities, glycogen, an irregular cell surface, focal lamina and multiple attachment plaques alternating with plasmalemmal caveolae. Some cells had a lesser expression of these markers, especially of myofilaments, and were regarded as poorly differentiated smooth-muscle cells and descriptively referred to as 'myoid'. Other cells were fibroblastic to judge by prominent rough endoplasmic reticulum, an absence of myofilaments and lamina, but presence of focal adhesions. The fibronexus junctions of true myofibroblasts were not seen. The study emphasises that the smooth-muscle actin immunoreactivity in this anatomical site resides in smooth-muscle cells and not in myofibroblasts, a view consistent with earlier ultrastructural and immunostaining results. The recognition that these cells are showing smooth-muscle or fibroblastic but not true myofibroblastic differentiation should inform our understanding of the function of these cells.

Fig 1

Classical arrangement of a subepithelial stromal cell (*) in relation to basal region of epithelium containing goblet cells. Note that there is a slender cell process (arrow) nearer the epithelium, which also belongs to a subepithelial stromal cell. Normal colon, case 15. Bar, 2 μm.

Fig 2

Subepithelial stromal cell process containing prominent rER (arrows) and showing a short stretch of external lamina (arrowheads). Normal small intestine, case 11. Bar, 1 μm.

Fig 3

A subepithelial stromal cell showing the concertina-nucleus typical of a smooth-muscle cell. The cytoplasm contains rER (*) and some peripheral myofilaments with focal densities (arrows). Normal duodenum, case 5. Bar, 1 μm.

Fig 4

Subepithelial stromal cell profile showing a stretch of external lamina, faithfully following the cell surface contour (arrowheads) and containing modestly developed myofilaments with focal densities (arrow). E: epithelium. Normal duodenum, case 5. Bar 500 nm.

Fig 5

(A) (top): A subepithelial stromal cell process 300 nm away from the epithelial basal lamina (arrow) at its closest point, and showing unambiguous smooth-muscle features – prominent smooth-muscle myofilaments with focal densities, glycogen, attachment plaques, an irregular cell surface and foci of lamina (arrowhead). (B) (bottom): Details of lamina (arrowheads) and glycogen. Normal rectum, case 21. Bar, 1 μm (A) and 500 nm (B).

Fig 6

(A) (top): Cell processes and a nucleated cell profile. Closest to the epithelium (∼80 nm) are slender subepithelial stromal cell processes of indeterminate nature (arrows). Next, in terms of distance from the epithelium, is a slender cell process (*) showing smooth-muscle features (many myofilaments and multiple attachment plaques). This is ∼1.3 μm from the basal lamina at its nearest and so by definition is subepithelial. Then, there is a cell process ∼5 μm away from the basal lamina, and is also therefore, by definition, subepithelial: it is of fibroblastic appearance – no lamina or filaments, but focal adhesions (circles). Finally, at the bottom of the figure is an interstitial stromal cell, ∼10 μm distant from the basal lamina, with unambiguous smooth-muscle features (prominent myofilaments and attachment plaques, arrowheads). (B) (bottom): Details of Figure 6A showing lamina (arrowhead), myofilaments and plasmalemmal caveolae (arrow) of the smooth-muscle type subepithelial stromal cell and the focal adhesions (circles) of the fibroblastic subepithelial stromal cell process. Normal colon, case 15. Bar, 1 μm.

Fig 7

An interstitial stromal cell with the appearance of a fibroblast – rER (arrows) and focal adhesions (circle). Normal colon, case 15. Bar, 1 μm.