Abstracts: 13 Role of local progenitors in the sustenance of networks of interstitial cells of Cajal (ICC) in the murine stomach

• Published in: Neurogastroenterology and motility 2006-06, Vol.18 (6), p.484-484
• Main Authors: L[Odblac]Rincz, A, Redelman, D, Horvath, V J, Bardsley, M R, Chen, H, Oerdoeg, T
• Format: Article
• Language: English
• Subjects: Simian virus 40
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/j.1365-2982.2006.00789_13.x

Depletion of ICC networks and consequent changes in electrical slow wave activity and neuromuscular neurotransmission play important roles in diabetic and idiopathic gastroparesis. We have shown that reduced insulin/IGF-I signaling and consequent decrease in stem cell factor (SCF) production underlie the ICC depletion of diabetic gastroparesis. It is, however, unclear whether the ICC loss is caused primarily by the accelerated attrition of mature cells or their impaired regeneration. In this study we identified local ICC progenitors and studied their role in the sustenance of gastric ICC networks. We investigated the expression of CD34, a putative marker for ICC precursors, and receptors for SCF (Kit), insulin, and IGF-I in murine gastric muscles by flow cytometry and immunohistochemistry. In freshly dissected tissues, CD34 was not detected in Kit super(Bright) ICC but a small population of Kit super(Low) cells expressed high levels of CD34. These cells were oval-shaped, had no processes, and occurred in small clusters on the serosal and submucosal surfaces of the gastric musculature and in the myenteric region. Unlike mature ICC, they expressed insulin and IGF-I receptors. Kit super(Low)CD34 super(+) cells were undetectable and Kit super(+) ICC were profoundly reduced in gastric muscles cultured in the absence of growth factors for up to 85 days. Soluble SCF added to the culture media for 32-85 days rescued Kit super(Low)CD34 super(+) cells and caused their growth into densely packed clusters in the myenteric region or thick chords containing bipolar cells within the muscle layers. These cells had elevated Kit and reduced CD34 expression. Cultures treated in a similar manner with IGF-I to stimulate both soluble and membrane-bound SCF were dominated by normal, Kit super(+)CD34 super(-) ICC networks. IGF-I treatments were only effective when initiated within the first 2-4 weeks of culturing, although mature, Kit super(+) ICC were able to survive longer. In adult H-2K super(b)-tsA58 mice harbouring the temperature-sensitive large tumour antigen encoded by a mutant strain of simian virus 40, stimulating cell proliferation by culturing at 33 degree C prevented the decline of gastric ICC even in the absence of exogenous growth factors. We conclude that maintenance of gastric ICC probably involves their regeneration from rare Kit super(Low)CD34 super(+) precursors that depend on a nearly uninterrupted supply of insulin or IGF-I. While the development of these ce