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Development of c-kit immunopositive interstitial cells of Cajal in the human stomach.

Radenkovic G, Savic V, Mitic D, Grahovac S, Bjelakovic M, Krstic M - J. Cell. Mol. Med. (2010)

Bottom Line: Between 9 and 11 weeks some of these precursors differentiated into ICC.In the fourth month, all subtypes of c-kit-immunoreactivity ICC which are necessary for the generation of slow waves and their transfer to SMC have been developed.These results may help elucidate the origin of ICC and the aetiology and pathogenesis of stomach motility disorders in neonates and young children that are associated with absence or decreased number of these cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Nis, Nis, Serbia. radenkog@scnet.yu

ABSTRACT
Interstitial cells of Cajal (ICC) include several types of specialized cells within the musculature of the gastrointestinal tract (GIT). Some types of ICC act as pacemakers in the GIT musculature, whereas others are implicated in the modulation of enteric neurotransmission. Kit immunohistochemistry reliably identifies the location of these cells and provides information on changes in ICC distribution and density. Human stomach specimens were obtained from 7 embryos and 28 foetuses without gastrointestinal disorders. The specimens were 7-27 weeks of gestational age, and both sexes are represented in the sample. The specimens were exposed to anti-c-kit antibodies to investigate ICC differentiation. Enteric plexuses were immunohistochemically examined by using anti-neuron specific enolase and the differentiation of smooth muscle cells (SMC) was studied with anti-alpha smooth muscle actin and anti-desmin antibodies. By week 7, c-kit-immunopositive precursors formed a layer in the outer stomach wall around myenteric plexus elements. Between 9 and 11 weeks some of these precursors differentiated into ICC. ICC at the myenteric plexus level differentiated first, followed by those within the muscle layer: between SMC, at the circular and longitudinal layers, and within connective tissue septa enveloping muscle bundles. In the fourth month, all subtypes of c-kit-immunoreactivity ICC which are necessary for the generation of slow waves and their transfer to SMC have been developed. These results may help elucidate the origin of ICC and the aetiology and pathogenesis of stomach motility disorders in neonates and young children that are associated with absence or decreased number of these cells.

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c-kit immunohistochemistry. (A–L) Embryos and foetuses aged 7–14 weeks. (A) 7 weeks, antrum. C-kit-IR cells located in the external portion of the stomach wall, on both sides of a group of myenteric plexus elements. These cells can be considered ICC precursors. (B) 8 weeks, corpus. C-kit immunopositive cells are grouped at the myenteric plexus, enveloping a ganglion. These cells have small triangular body with three or more thin processes. (C) 8 weeks. The belt of c-kit-IR cells is present throughout the stomach circumference, except in the fundus, where it is very thin or absent. (D) 9 weeks, antrum. C-kit immunopositive cells are located external to the grouped myoblasts of the circular layer. (E) 8 weeks, corpus. C-kit-IR cell (arrow) with at least three processes. (F) 8 weeks, corpus. C-kit-IR cell (arrow) with at least three processes. (G) 11 weeks. An ICC-MP with three processes (arrow), one of which bifurcates. (H) 11 weeks, corpus. One spindle-shaped ICC-MP (arrow) with two primary processes that branch further into secondary processes. (I) 11 weeks, corpus. Four highly ramified ICC-MP, one of which has at least four processes (arrow). (J) 14 weeks, corpus. In the submucosa, isolated round c-kit-IR mast cell is seen. (K) 11 weeks, corpus. The arrow indicates ICC closely apposed around a ganglion. These cells can be considered ICC-MP. (L) 12 weeks, antrum. Two spindle-shaped ICC-CM (arrows) within the circular muscle layer. CM, circular muscle layer; MP, myenteric plexus; SM, submucosa; L, lumen; Li, liver; Ca, cardias; F, fundus; Co, corpus; A, antrum. Bar: A, D = 50 μm; B, K, L = 25 μm; C = 250 μm; E–J = 20 μm.
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fig01: c-kit immunohistochemistry. (A–L) Embryos and foetuses aged 7–14 weeks. (A) 7 weeks, antrum. C-kit-IR cells located in the external portion of the stomach wall, on both sides of a group of myenteric plexus elements. These cells can be considered ICC precursors. (B) 8 weeks, corpus. C-kit immunopositive cells are grouped at the myenteric plexus, enveloping a ganglion. These cells have small triangular body with three or more thin processes. (C) 8 weeks. The belt of c-kit-IR cells is present throughout the stomach circumference, except in the fundus, where it is very thin or absent. (D) 9 weeks, antrum. C-kit immunopositive cells are located external to the grouped myoblasts of the circular layer. (E) 8 weeks, corpus. C-kit-IR cell (arrow) with at least three processes. (F) 8 weeks, corpus. C-kit-IR cell (arrow) with at least three processes. (G) 11 weeks. An ICC-MP with three processes (arrow), one of which bifurcates. (H) 11 weeks, corpus. One spindle-shaped ICC-MP (arrow) with two primary processes that branch further into secondary processes. (I) 11 weeks, corpus. Four highly ramified ICC-MP, one of which has at least four processes (arrow). (J) 14 weeks, corpus. In the submucosa, isolated round c-kit-IR mast cell is seen. (K) 11 weeks, corpus. The arrow indicates ICC closely apposed around a ganglion. These cells can be considered ICC-MP. (L) 12 weeks, antrum. Two spindle-shaped ICC-CM (arrows) within the circular muscle layer. CM, circular muscle layer; MP, myenteric plexus; SM, submucosa; L, lumen; Li, liver; Ca, cardias; F, fundus; Co, corpus; A, antrum. Bar: A, D = 50 μm; B, K, L = 25 μm; C = 250 μm; E–J = 20 μm.

Mentions: In this period of development, c-kit-IR was observed in the form of a wide belt of cells situated at the level of the myenteric plexus (Fig. 1A–C). Within the belt of c-kit-IR cells are clearly delineated groups of c-kit– cells, surrounded by, but not interspersed with, c-kit-IR cells (Fig. 1A and B). The described groups of c-kit-IR– cells are NSE-IR, confirming that they represent the inception of the myenteric plexus ganglia.


Development of c-kit immunopositive interstitial cells of Cajal in the human stomach.

Radenkovic G, Savic V, Mitic D, Grahovac S, Bjelakovic M, Krstic M - J. Cell. Mol. Med. (2010)

c-kit immunohistochemistry. (A–L) Embryos and foetuses aged 7–14 weeks. (A) 7 weeks, antrum. C-kit-IR cells located in the external portion of the stomach wall, on both sides of a group of myenteric plexus elements. These cells can be considered ICC precursors. (B) 8 weeks, corpus. C-kit immunopositive cells are grouped at the myenteric plexus, enveloping a ganglion. These cells have small triangular body with three or more thin processes. (C) 8 weeks. The belt of c-kit-IR cells is present throughout the stomach circumference, except in the fundus, where it is very thin or absent. (D) 9 weeks, antrum. C-kit immunopositive cells are located external to the grouped myoblasts of the circular layer. (E) 8 weeks, corpus. C-kit-IR cell (arrow) with at least three processes. (F) 8 weeks, corpus. C-kit-IR cell (arrow) with at least three processes. (G) 11 weeks. An ICC-MP with three processes (arrow), one of which bifurcates. (H) 11 weeks, corpus. One spindle-shaped ICC-MP (arrow) with two primary processes that branch further into secondary processes. (I) 11 weeks, corpus. Four highly ramified ICC-MP, one of which has at least four processes (arrow). (J) 14 weeks, corpus. In the submucosa, isolated round c-kit-IR mast cell is seen. (K) 11 weeks, corpus. The arrow indicates ICC closely apposed around a ganglion. These cells can be considered ICC-MP. (L) 12 weeks, antrum. Two spindle-shaped ICC-CM (arrows) within the circular muscle layer. CM, circular muscle layer; MP, myenteric plexus; SM, submucosa; L, lumen; Li, liver; Ca, cardias; F, fundus; Co, corpus; A, antrum. Bar: A, D = 50 μm; B, K, L = 25 μm; C = 250 μm; E–J = 20 μm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3822749&req=5

fig01: c-kit immunohistochemistry. (A–L) Embryos and foetuses aged 7–14 weeks. (A) 7 weeks, antrum. C-kit-IR cells located in the external portion of the stomach wall, on both sides of a group of myenteric plexus elements. These cells can be considered ICC precursors. (B) 8 weeks, corpus. C-kit immunopositive cells are grouped at the myenteric plexus, enveloping a ganglion. These cells have small triangular body with three or more thin processes. (C) 8 weeks. The belt of c-kit-IR cells is present throughout the stomach circumference, except in the fundus, where it is very thin or absent. (D) 9 weeks, antrum. C-kit immunopositive cells are located external to the grouped myoblasts of the circular layer. (E) 8 weeks, corpus. C-kit-IR cell (arrow) with at least three processes. (F) 8 weeks, corpus. C-kit-IR cell (arrow) with at least three processes. (G) 11 weeks. An ICC-MP with three processes (arrow), one of which bifurcates. (H) 11 weeks, corpus. One spindle-shaped ICC-MP (arrow) with two primary processes that branch further into secondary processes. (I) 11 weeks, corpus. Four highly ramified ICC-MP, one of which has at least four processes (arrow). (J) 14 weeks, corpus. In the submucosa, isolated round c-kit-IR mast cell is seen. (K) 11 weeks, corpus. The arrow indicates ICC closely apposed around a ganglion. These cells can be considered ICC-MP. (L) 12 weeks, antrum. Two spindle-shaped ICC-CM (arrows) within the circular muscle layer. CM, circular muscle layer; MP, myenteric plexus; SM, submucosa; L, lumen; Li, liver; Ca, cardias; F, fundus; Co, corpus; A, antrum. Bar: A, D = 50 μm; B, K, L = 25 μm; C = 250 μm; E–J = 20 μm.
Mentions: In this period of development, c-kit-IR was observed in the form of a wide belt of cells situated at the level of the myenteric plexus (Fig. 1A–C). Within the belt of c-kit-IR cells are clearly delineated groups of c-kit– cells, surrounded by, but not interspersed with, c-kit-IR cells (Fig. 1A and B). The described groups of c-kit-IR– cells are NSE-IR, confirming that they represent the inception of the myenteric plexus ganglia.

Bottom Line: Between 9 and 11 weeks some of these precursors differentiated into ICC.In the fourth month, all subtypes of c-kit-immunoreactivity ICC which are necessary for the generation of slow waves and their transfer to SMC have been developed.These results may help elucidate the origin of ICC and the aetiology and pathogenesis of stomach motility disorders in neonates and young children that are associated with absence or decreased number of these cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Nis, Nis, Serbia. radenkog@scnet.yu

ABSTRACT
Interstitial cells of Cajal (ICC) include several types of specialized cells within the musculature of the gastrointestinal tract (GIT). Some types of ICC act as pacemakers in the GIT musculature, whereas others are implicated in the modulation of enteric neurotransmission. Kit immunohistochemistry reliably identifies the location of these cells and provides information on changes in ICC distribution and density. Human stomach specimens were obtained from 7 embryos and 28 foetuses without gastrointestinal disorders. The specimens were 7-27 weeks of gestational age, and both sexes are represented in the sample. The specimens were exposed to anti-c-kit antibodies to investigate ICC differentiation. Enteric plexuses were immunohistochemically examined by using anti-neuron specific enolase and the differentiation of smooth muscle cells (SMC) was studied with anti-alpha smooth muscle actin and anti-desmin antibodies. By week 7, c-kit-immunopositive precursors formed a layer in the outer stomach wall around myenteric plexus elements. Between 9 and 11 weeks some of these precursors differentiated into ICC. ICC at the myenteric plexus level differentiated first, followed by those within the muscle layer: between SMC, at the circular and longitudinal layers, and within connective tissue septa enveloping muscle bundles. In the fourth month, all subtypes of c-kit-immunoreactivity ICC which are necessary for the generation of slow waves and their transfer to SMC have been developed. These results may help elucidate the origin of ICC and the aetiology and pathogenesis of stomach motility disorders in neonates and young children that are associated with absence or decreased number of these cells.

Show MeSH
Related in: MedlinePlus