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Igf1r+/CD34+ immature ICC are putative adult progenitor cells, identified ultrastructurally as fibroblast-like ICC in Ws/Ws rat colon.

Wang XY, Albertí E, White EJ, Mikkelsen HB, Larsen JO, Jiménez M, Huizinga JD - J. Cell. Mol. Med. (2009)

Bottom Line: A significantly higher number of Igf1r(+)/CD34(+) cells were found in Ws/Ws compared to wild-type rat colons.Immunohistochemistry revealed a reduction of neurons positive for neuronal nitric oxide synthase.The reduction in nitrergic innervation associated with the Ws mutation may be the result of a reduction in nitrergic neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT
The colon of Ws/Ws mutant rats shows impairment of pacemaker activity and altered inhibitory neurotransmission. The present study set out to find structural correlates to these findings to resolve mechanisms. In the colon of Ws/Ws rats, interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP) were significantly decreased and ICC located at the submuscular plexus and intramuscular ICC were rarely observed based on immunohistochemistry and electron microscopy. Ultrastructural investigations revealed that there was no overall loss of all types of interstitial cells combined. Where loss of ICC was observed, a marked increase in fibroblast-like ICC (FL-ICC) was found at the level of AP. Immunoelectron microscopy proved FL-ICC to be c-Kit(-) but gap junction coupled to each other and to c-Kit(+) ICC; they were associated with enteric nerves and occupied space normally occupied by ICC in the wild-type rat colon, suggesting them to be immature ICC. In addition, a marked increase in immunoreactivity for insulin-like growth factor 1 receptor (Igf1r) occurred, co-localized with CD34 but not with c-Kit. A significantly higher number of Igf1r(+)/CD34(+) cells were found in Ws/Ws compared to wild-type rat colons. These CD34(+)/Igf1r(+) cells in the Ws/Ws colon occupied the same space as FL-ICC. Hence we propose that a subset of immature ICC (FL-ICC) consists of adult progenitor cells. Immunohistochemistry revealed a reduction of neurons positive for neuronal nitric oxide synthase. The functional capabilities of the immature ICC and the regenerative capabilities of the adult progenitor cells need further study. The morphological features described here show that the loss of pacemaker activity is not associated with failure to develop a network of interstitial cells around AP but a failure to develop this network into fully functional pacemaker cells. The reduction in nitrergic innervation associated with the Ws mutation may be the result of a reduction in nitrergic neurons.

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c-Kit immuno EM pictures showing c-Kit+ ICC in wild-type proximal colon and c-Kit– FL-ICC in Ws/Ws mid colon. (a) A c-Kit+ ICC-AP (ICC, dark stained with DAB) situated at a ganglion in Auerbach’s plexus. Many caveolae (small arrows) were located along the membrane of the c-Kit+ ICC. (b). A c-Kit– FL-ICC was also close to a myenteric ganglion. Nearby was a c-Kit+ ICC-AP (ICC, dark stained) which was crossed over by a muscle bundle (SM). The processes of ICC and FL-ICC were directly contacting each other (arrow).
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fig08: c-Kit immuno EM pictures showing c-Kit+ ICC in wild-type proximal colon and c-Kit– FL-ICC in Ws/Ws mid colon. (a) A c-Kit+ ICC-AP (ICC, dark stained with DAB) situated at a ganglion in Auerbach’s plexus. Many caveolae (small arrows) were located along the membrane of the c-Kit+ ICC. (b). A c-Kit– FL-ICC was also close to a myenteric ganglion. Nearby was a c-Kit+ ICC-AP (ICC, dark stained) which was crossed over by a muscle bundle (SM). The processes of ICC and FL-ICC were directly contacting each other (arrow).

Mentions: At the level of Auerbach’s plexus in the Ws/Ws colon, both typical ICC-AP (Fig. 7c) and FL-ICC (Fig. 7d) were observed. Immuno EM showed typical ICC to be c-Kit+ (Fig. 8a and b) and FL-ICC to be c-Kit– (Fig. 8b). At the SMP of Ws/Ws colon, many interstitial cells were found associated with nerve structures (Fig. 9d). There were almost no typical and ultrastructurally defined ICC-SMP as in wild-type colon (Fig. 9a). Most of the interstitial cells in this region were FL-ICC (Fig. 9b–d), which were connected to each other (Fig. 9d). In many profiles, the only feature different from typical ICC was an absence of caveolae (Fig. 9c). Fibroblasts (Fig. 9c) and macrophage-like cells (not shown) were also observed at the level of the SMP.


Igf1r+/CD34+ immature ICC are putative adult progenitor cells, identified ultrastructurally as fibroblast-like ICC in Ws/Ws rat colon.

Wang XY, Albertí E, White EJ, Mikkelsen HB, Larsen JO, Jiménez M, Huizinga JD - J. Cell. Mol. Med. (2009)

c-Kit immuno EM pictures showing c-Kit+ ICC in wild-type proximal colon and c-Kit– FL-ICC in Ws/Ws mid colon. (a) A c-Kit+ ICC-AP (ICC, dark stained with DAB) situated at a ganglion in Auerbach’s plexus. Many caveolae (small arrows) were located along the membrane of the c-Kit+ ICC. (b). A c-Kit– FL-ICC was also close to a myenteric ganglion. Nearby was a c-Kit+ ICC-AP (ICC, dark stained) which was crossed over by a muscle bundle (SM). The processes of ICC and FL-ICC were directly contacting each other (arrow).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4516506&req=5

fig08: c-Kit immuno EM pictures showing c-Kit+ ICC in wild-type proximal colon and c-Kit– FL-ICC in Ws/Ws mid colon. (a) A c-Kit+ ICC-AP (ICC, dark stained with DAB) situated at a ganglion in Auerbach’s plexus. Many caveolae (small arrows) were located along the membrane of the c-Kit+ ICC. (b). A c-Kit– FL-ICC was also close to a myenteric ganglion. Nearby was a c-Kit+ ICC-AP (ICC, dark stained) which was crossed over by a muscle bundle (SM). The processes of ICC and FL-ICC were directly contacting each other (arrow).
Mentions: At the level of Auerbach’s plexus in the Ws/Ws colon, both typical ICC-AP (Fig. 7c) and FL-ICC (Fig. 7d) were observed. Immuno EM showed typical ICC to be c-Kit+ (Fig. 8a and b) and FL-ICC to be c-Kit– (Fig. 8b). At the SMP of Ws/Ws colon, many interstitial cells were found associated with nerve structures (Fig. 9d). There were almost no typical and ultrastructurally defined ICC-SMP as in wild-type colon (Fig. 9a). Most of the interstitial cells in this region were FL-ICC (Fig. 9b–d), which were connected to each other (Fig. 9d). In many profiles, the only feature different from typical ICC was an absence of caveolae (Fig. 9c). Fibroblasts (Fig. 9c) and macrophage-like cells (not shown) were also observed at the level of the SMP.

Bottom Line: A significantly higher number of Igf1r(+)/CD34(+) cells were found in Ws/Ws compared to wild-type rat colons.Immunohistochemistry revealed a reduction of neurons positive for neuronal nitric oxide synthase.The reduction in nitrergic innervation associated with the Ws mutation may be the result of a reduction in nitrergic neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT
The colon of Ws/Ws mutant rats shows impairment of pacemaker activity and altered inhibitory neurotransmission. The present study set out to find structural correlates to these findings to resolve mechanisms. In the colon of Ws/Ws rats, interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP) were significantly decreased and ICC located at the submuscular plexus and intramuscular ICC were rarely observed based on immunohistochemistry and electron microscopy. Ultrastructural investigations revealed that there was no overall loss of all types of interstitial cells combined. Where loss of ICC was observed, a marked increase in fibroblast-like ICC (FL-ICC) was found at the level of AP. Immunoelectron microscopy proved FL-ICC to be c-Kit(-) but gap junction coupled to each other and to c-Kit(+) ICC; they were associated with enteric nerves and occupied space normally occupied by ICC in the wild-type rat colon, suggesting them to be immature ICC. In addition, a marked increase in immunoreactivity for insulin-like growth factor 1 receptor (Igf1r) occurred, co-localized with CD34 but not with c-Kit. A significantly higher number of Igf1r(+)/CD34(+) cells were found in Ws/Ws compared to wild-type rat colons. These CD34(+)/Igf1r(+) cells in the Ws/Ws colon occupied the same space as FL-ICC. Hence we propose that a subset of immature ICC (FL-ICC) consists of adult progenitor cells. Immunohistochemistry revealed a reduction of neurons positive for neuronal nitric oxide synthase. The functional capabilities of the immature ICC and the regenerative capabilities of the adult progenitor cells need further study. The morphological features described here show that the loss of pacemaker activity is not associated with failure to develop a network of interstitial cells around AP but a failure to develop this network into fully functional pacemaker cells. The reduction in nitrergic innervation associated with the Ws mutation may be the result of a reduction in nitrergic neurons.

Show MeSH
Related in: MedlinePlus