Interstitial cells of Cajal (ICC) are critical to gastrointestinal motility. of ICC in the proximal segment of the HSCR colon were lower than in the adult normal colon. Ultrastructurally, ICC, enteric nerves, and smooth muscle in the narrow segment Rabbit Polyclonal to TAF3 of the HSCR colon showed severe injury, including swollen vacuola or ted mitochondria, disappearance of mitochondrial cristae, dilated rough endoplasmic reticulum, vesiculation and degranulation, and disappearance of the on the ICC membrane surface. The contents of ICC and its progenitors in the narrow part of the HSCR colon were significantly decreased than those of adult colon, which may be associated with HSCR pathogenesis. Introduction Interstitial cells of Cajal (ICC) located between gut nerve fibers and smooth muscle cells play a critical role in gastrointestinal motility. They mediate both excitatory and inhibitory neuromuscular neurotransmission [1], [2]. Many studies support that ICC have regenerative capacity, which could restore their networks after gut injury [3], inflammation [4], [5] surgical transection and anastomosis [6], [7]. ICC depletion is probably Enzastaurin a key point in the pathogenesis of these disorders, and patients would benefit from its reversal. However, in other gastrointestinal motility disorders, the number of ICC is extremely reduced and difficult to reverse. These disorders include achalasia, diabetic and idiopathic gastroparesis, mechanical ileus, and intestinal pseudo-obstructions. Depletion of ICC could result from severe injury of mature cells and/or impaired regeneration of progenitor cells. Hirschsprungs disease (HSCR) is a congenital disorder of the colon, causing chronic constipation. Its incidence is about 15000 in the United States, but around the world incidence ranges from about 11000 to 110,000. Children with HSCR often have the following symptoms: delayed passage of meconium (>24 Enzastaurin hours from birth), neonatal bowel obstruction (abdominal distension, green or yellow vomiting), constipation that does not respond to oral medicines, poor growth, and sometimes loose bowel movements with blood and accompanying fever. Currently, clinical diagnosis of HSCR is based on the lack of ganglion cells at the myenteric and submucosal plexus. Previous reports have shown that there were alterations of ganglion cell genes, such as RET, PHOX2B, HOX and NGR3 which are associated with the Hirschsprungs disease [7]C[10]. However, these results are obtained from blood drawn from patient and not fresh colon tissue. Researchers have tried the therapy of enteric nervous Enzastaurin system stem cells (ENSSCs), but previous animal models have failed to completely restore the intestinal physiological function after transplantation [11]C[14]. We suggest that there is another critical point in HSCR guts, the ICC network that requires repair. The number of ICC has been found to be remarkably reduced in the narrow segment of the HSCR colon, which is pathologic [15]C[18]. ICC develop prenatally from c-Kit+ (also named CD117) mesoderm mesenchymal progenitors [19], [20]. Intramuscular ICC of the foregut may also be derived from ventrally emigrating neural tube cells [21], [22]. Progenitors of ICC committed to become mature ICC have been reported during the early postnatal period [23], [24]. ICC from mouse gut showed proliferation that was SCF and IGF-I dose-dependent and time-limited [25], [26]. Recently, two studies brought to light that defects of ICC can be repaired by bone marrow mesenchymal stem cells (BMSC) [27], [28]. It was speculated that.