Development of C-Kit Immunopositive Interstitial Cells of Cajal in the Human Stomach

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-α 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.

The Significance of Interstitial Cells in Neurogastroenterology

“…[68][69][70][71][72] In larger animals the muscle layers are much thicker than in rodents and it has been suggested that the function of septal ICC is to facilitate propagation of slow waves through the muscle layer. 65,68 Thus, ICC-SEP may provide a Purkinje cell-like function to facilitate slow wave propagation and coordinate excitation-contraction coupling through the entire thickness of the muscle.…”

Interstitial cells of Cajal (ICC)-like-c-Kit positive cells are involved in gastritis and carcinogenesis in human stomach

“…Therefore, antibodies against c-Kit are useful for the identification of ICC (2,3). c-Kit is a transmembrane tyrosine kinase receptor (rTK) and its activation by the stem cell factor (SCf) is essential for survival, maintenance of the phenotype and pacemaking activity of ICC (4). Apart from ICC, however, c-Kit and/or SCf are also expressed in a variety of normal tissues such as placenta and lung (16) and also in gastric carcinoma cell lines (17).…”

Regional Distribution of Interstitial Cells of Cajal (ICC) in Human Stomach

“…c-Kit is essential for the maintenance of normal hematopoiesis, melanogenesis and differentiation of mast cell and ICC [24]. Since c-Kit is known to maintain their proliferation, migration, and survival [4], the malfunction of c-Kit is thought to be associated also with a certain neoplastic disorders and gastric dysmotility in mucosa, microvilli, submucosal plexus and muscularis mucosa [1,21,22]. There is one more type of muscle in muscular layer of human gastric wall, also called oblique muscle, which is more prominent in fundus than corpus.…”

“…Therefore, a blockade of c-Kit with neutralizing antibodies [11] and/or mutations of c-Kit or Steel [7] impair normal development of ICC in the myenteric plexus region (ICC-MY) of small intestine. It was reported that all subtypes of ICC in human stomach are been developed as early as 4 th month developmental stage with their specific functions [4]. To date, at least two types of major ICC have been identified in the GI tract: One is ICC-MY of myenteric region, and the other is a second population of ICC which are distributed outside the myenteric region and is abundant in deep muscular plexus through the muscle layers (intramuscular ICC, ICC-IM).…”

“…It is the end of the last century where researchers began to assume ICC as a regulator of GI motility in animal, including humans, throughout from esophagus to anus [2][3][4][5][6]. Many studies indicated that ICC is the genuine pacemaker cells which generate spontaneous electrical activities, known as slow waves in GI tract [7,8].…”