Abstract
Surgical manipulations of the gastrointestinal (GI) tract usually lead to loss of interstitial cells of Cajal (ICCs). The present study prepared to investigate whether ICCs can regenerate and restore their normal distribution up to 5 months after semitransection and end-to-end anastomosis of small intestines of adult guinea pigs. The segments of anastomosis were studied by immunohistochemistry with anti-KIT, 5-bromo-2′-deoxyuridine (BrdU), stem cell factor (SCF), and neurofilament 200 antibodies and also by transmission electron microscopy (TEM). At early stage, intestinal surgery led to intestinal wall impairment and ICCs loss, and ICCs near the site of anastomosis gradually increased in numbers. About 150 days postoperation, the distribution of ICCs and the microstructure of intestinal wall appeared to be similar with those of the control. By double immunostaining with BrdU and KIT antibodies, a number of proliferated ICCs were seen near the site of transection/anastomosis. Furthermore, KIT ligand, SCF, was mainly observed in the smooth muscle cells (SMCs), which are located close to ICCs. TEM observation revealed a number of immature and mature ICCs in this region. Our results indicated that ICCs could regenerate and restore their normal distribution after intestinal surgery and SMCs might be involved in the regenerated events of ICCs in the adult guinea pig GI tract.
Similar content being viewed by others
Abbreviations
- DMP:
-
Deep muscular plexus
- GI:
-
Gastrointestinal
- ICCs:
-
Interstitial cells of Cajal
- IM:
-
Intramuscular
- MY:
-
Myenteric plexus
- SCF:
-
Stem cell factor
- SMCs:
-
Smooth muscle cells
References
Baig MK, Wexner SD (2004) Postoperative ileus: a review. Dis Colon Rectum 47:516–526
Beckett EA, Horiguchi K, Khoyi M, Sanders KM, Ward SM (2002) Loss of enteric motor neurotransmission in the gastric fundus of Sl/Sl(d) mice. J Physiol 543:871–887
Behm B, Stollman N (2003) Postoperative ileus: etiologies and interventions. Clin Gastroenterol Hepatol 1:71–80
Bharucha AE, Philips SF (2001) Slow-transit constipation. Curr Treat Options Gastroenterol 4:309–315
Chang IY, Glasgow NJ, Takayama I, Horiguchi K, Sanders KM, Ward SM (2001) Loss of interstitial cells of Cajal and development of electrical dysfunction in murine small bowel obstruction. J Physiol 536:555–568
Faussone-Pellegrini MS, Gay J, Vannucchi MG, Corsani L, Fioramonti J (2002) Alterations of neurokinin receptors and interstitial cells of Cajal during and after jejunal inflammation induced by Nippostrongylus brasiliensis in the rat. Neurogastroenterol Motil 14:83–95
Isozaki K, Hirota S, Miyagawa J, Taniguchi M, Shinomura Y, Matsuzawa Y (1997) Deficiency of c-kit+ cells in patients with a myopathic form of chronic idiopathic intestinal pseudo-obstruction. Am J Gastroenterol 92:332–334
Kito Y, Ward SM, Sanders KM (2005) Pacemaker potentials generated by interstitial cells of Cajal in the murine intestine. Am J Physiol Cell Physiol 288:C710–C720
Kluppel M, Huizinga JD, Malysz J, Bernstein A (1998) Developmental origin and Kit-dependent development of the interstitial cells of Cajal in the mammalian small intestine. Dev Dyn 211:60–71
Komuro T, Zhou DS (1996) Anti-c-kit protein immunoreactive cells corresponding to the interstitial cells of Cajal in the guinea-pig small intestine. J Auton Nerv Syst 61:169–174
Lecoin L, Gabella G, Le Douarin N (1996) Origin of the c-kit-positive interstitial cells in the avian bowel. Development 122:725–733
Liu LW, Thuneberg L, Huizinga JD (1998) Development of pacemaker activity and interstitial cells of Cajal in the neonatal mouse small intestine. Dev Dyn 213:271–282
Mikkelsen HB, Malysz J, Huizinga JD, Thuneberg L (1998) Action potential generation, kit receptor immunohistochemistry and morphology of steel-Dickie (Sl/Sld) mutant mouse small intestine. Neurogastroenterol Motil 10:11–26
Nakahara M, Isozaki K, Vanderwinden JM, Shinomura Y, Kitamura Y, Hirota S, Matsuzawa Y (2002) Dose-dependent and time-limited proliferation of cultured murine interstitial cells of Cajal in response to stem cell factor. Life Sci 70:2367–2376
Rolle U, Piotrowska AP, Nemeth L, Puri P (2002) Altered distribution of interstitial cells of Cajal in Hirschsprung disease. Arch Pathol Lab Med 126:928–933
Sanders KM, Ordog T, Koh SD, Torihashi S, Ward SM (1999) Development and plasticity of interstitial cells of Cajal. Neurogastroenterol Motil 11:311–338
Sanders KM, Ordog T, Ward SM (2002) Physiology and pathophysiology of the interstitial cells of Cajal: from bench to bedside. IV. Genetic and animal models of GI motility disorders caused by loss of interstitial cells of Cajal. Am J Physiol Gastrointest Liver Physiol 282:G747–G756
Torihashi S, Ward SM, Nishikawa S, Nishi K, Kobayashi S, Sanders KM (1995) c-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract. Cell Tissue Res 280:97–111
Torihashi S, Yoshida H, Nishikawa S, Kunisada T, Sanders KM (1996) Enteric neurons express steel factor-lacZ transgene in the murine gastrointestinal tract. Brain Res 738:323–328
Torihashi S, Ward SM, Sanders KM (1997) Development of c-Kit-positive cells and the onset of electrical rhythmicity in murine small intestine. Gastroenterology 112:144–155
Tsukamoto K, Mizutani M, Yamano M, Tagi Y, Takeda M (2000) The effect of SK-896 on post-operative ileus in dogs: gastrointestinal motility pattern and transit. Eur J Pharmacol 401:97–107
van der Velden MA, Klein WR (1993) The effects of cisapride on the restoration of gut motility after surgery of the small intestine in horses; a clinical trial. Vet Q 15:175–179
Ward SM, Burns AJ, Torihashi S, Sanders KM (1994) Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol 480(Pt 1):91–97
Ward SM, Burns AJ, Torihashi S, Harney SC, Sanders KM (1995) Impaired development of interstitial cells and intestinal electrical rhythmicity in steel mutants. Am J Physiol 269:C1577–C1585
Ward SM, Ordog T, Bayguinov JR, Horowitz B, Epperson A, Shen L, Westphal H, Sanders KM (1999) Development of interstitial cells of Cajal and pacemaking in mice lacking enteric nerves. Gastroenterology 117:584–594
Ward SM, Beckett EA, Wang X, Baker F, Khoyi M, Sanders KM (2000) Interstitial cells of Cajal mediate cholinergic neurotransmission from enteric motor neurons. J Neurosci 20:1393–1403
Wester T, Eriksson L, Olsson Y, Olsen L (1999) Interstitial cells of Cajal in the human fetal small bowel as shown by c-kit immunohistochemistry. Gut 44:65–71
Wu JJ, Rothman TP, Gershon MD (2000) Development of the interstitial cell of Cajal: origin, kit dependence and neuronal and nonneuronal sources of kit ligand. J Neurosci Res 59:384–401
Yamataka A, Kato Y, Tibboel D, Murata Y, Sueyoshi N, Fujimoto T, Nishiye H, Miyano T (1995) A lack of intestinal pacemaker (c-kit) in aganglionic bowel of patients with Hirschsprung’s disease. J Pediatr Surg 30:441–444
Yanagida H, Yanase H, Sanders KM, Ward SM (2004) Intestinal surgical resection disrupts electrical rhythmicity, neural responses, and interstitial cell networks. Gastroenterology 127:1748–1759
Young HM, Ciampoli D, Southwell BR, Newgreen DF (1996) Origin of interstitial cells of Cajal in the mouse intestine. Dev Biol 180:97–107
Young HM, Torihashi S, Ciampoli D, Sanders KM (1998) Identification of neurons that express stem cell factor in the mouse small intestine. Gastroenterology 115:898–908
Acknowledgements
We thank Dr. Y. Tang (Department of Histology and Embryology, Chongqing University of Medical Sciences) for critical reading the manuscript. This work was supported in parts by grants no. 30470911 and 30570983 from the National Science Foundation of China (NSFC). Feng Mei and Bin Yu contributed equally to this work.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mei, F., Yu, B., Ma, H. et al. Interstitial cells of Cajal could regenerate and restore their normal distribution after disrupted by intestinal transection and anastomosis in the adult guinea pigs. Virchows Arch 449, 348–357 (2006). https://doi.org/10.1007/s00428-006-0258-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-006-0258-6