Progenitors of interstitial cells of Cajal in the postnatal murine stomach
Progenitors of interstitial cells of Cajal in the postnatal murine stomach
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DOI：
10.1053/j.gastro.2008.01.036
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发表时间：
2008-04-01
期刊：
影响因子：
29.4
通讯作者：
Ordog, Tamas
中科院分区：
文献类型：
--
作者：
Lorincz, Andrea;Redelman, Doug;Ordog, Tamas
背景与目的：维持Cajal间质细胞（ICC）网络的完整性对于维持胃肠道有序的收缩活动和神经调节以及在组织损伤或手术后恢复这些功能至关重要。ICC的维持需要依赖胰岛素或胰岛素样生长因子I （IGF-I）依赖膜结合干细胞因子（SCF）的产生，并可能涉及局部祖细胞的再生。我们的目的是鉴定出生后小鼠胃肌中的ICC前体。方法：采用流式细胞术和免疫组织化学方法检测新鲜解剖和培养的肌肉中表达间质肿瘤表达的黏附分子CD34的细胞；CD44，发生在间充质干细胞上；以及SCF （Kit）、胰岛素（Insr）和IGF-I （Igf1r）受体。细胞内记录慢波。结果：在胃肌肉中，我们发现了罕见的Kit（低）CD44(+)CD34(+)Insr(+) Igf1r（+）细胞，类似于ICC和平滑肌的常见胚胎前体。由于胰岛素/ IGF-I的长期剥夺，这些假定的祖细胞在缺乏成熟ICC (Kit(+)CD44(+)CD34(-)Insr（-)Igf1r(-)）的器官型培养中缺失，但被IGF-I拯救，也阻止了ICC的损失。可溶性SCF不能阻止成熟ICC的丢失，但显著地扩展了假定的祖细胞，尽管保留了不成熟的Kit(+)CD44(+)CD34(+)Insr(+) Igf1r+表型，但它支持强大的慢波活性。这些细胞分化为成熟的、形成网络的ICC需要IGF-I。相反，在长期胰岛素和IGF-I剥夺后，IGF-I恢复ICC网络需要假定的祖细胞的存活。结论：Kit(low)CD44(+)CD34(+) Insr(+)Igf1r（+）细胞可能是胃ICC和间质瘤的局部祖细胞。这些细胞的丧失可能导致胃肠功能障碍。
Background & Aims: Maintaining the integrity of networks of interstitial cells of Cajal (ICC) is essential to preserve orderly contractile activity and neuroregulation in the gastrointestinal tract and to restore these functions after tissue damage or surgeries. Maintenance of ICC requires insulin-dependent or insulin-like growth factor I (IGF-I)-dependent production of membrane-bound stem cell factor (SCF) and may involve regeneration from local progenitors. Our goal was to identify ICC precursors in postnatal murine gastric muscles. Methods: We used flow cytometry and immunohistochemistry to examine freshly dissected and cultured muscles for cells expressing CD34, an adhesion molecule expressed by stromal tumors; CD44, which occurs on mesenchymal stem cells; and receptors for SCF (Kit), insulin (Insr), and IGF-I (Igf1r). Slow waves were studied by intracellular recording. Results: in gastric muscles, we identified rare, Kit(low)CD44(+)CD34(+)Insr(+) Igf1r(+) cells resembling common embryonic precursors of ICC and smooth muscle. These putative progenitors were absent from organotypic cultures lacking mature ICC (Kit(+)CD44(+)CD34(-)Insr(-)Igf1r(-)) due to prolonged insulin/ IGF-I deprivation but were rescued by IGF-I that also prevented ICC loss. Soluble SCF failed to prevent the loss of mature ICC but dramatically expanded the putative progenitors, which supported robust slow wave activity despite retaining an immature, Kit(+)CD44(+)CD34(+)Insr(+) Igf1r+ phenotype. Differentiation of these cells into mature, network-forming ICC required IGF-I Conversely, restoration of ICC networks by IGF-I after prolonged insulin and IGF-I deprivation required the survival of the presumed progenitors. ConClusions: Kit(low)CD44(+)CD34(+) Insr(+)Igf1r(+) cells may be local progenitors for gastric ICC and stromal tumors. Loss of these cells may contribute to gastrointestinal dysmotilities.