3-D illustration of network orientations of interstitial cells of Cajal subgroups in human colon as revealed by deep-tissue imaging with optical clearing

Liu, Yuan An; Chung, Yuan Chiang; Pan, Shien Tung; Hou, Yung Chi; Peng, Shih-Jung; Pasricha, Pankaj J.; Tang, Shiue–Cheng

doi:10.1152/ajpgi.00432.2011

Cited by 26 publications

(22 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The study of the electrophysiology of human colonic muscle is obviously in its infancy. In contrast with subserous ICC in mouse, guinea pig, canine, and nonhuman primate colon [Toma et al, 1999;Vanderwinden et al, 2000b;Aranishi et al, 2009;Lee et al, 2009;Chan et al, 2010;Han et al, 2010;Blair et al, 2012a], but in accordance with subserous interstitial cells in mouse internal anal sphincter [Cobine et al, 2011], IC-SS of the human colon are apparently Kit negative [He et al, 2000;Pieri et al, 2008;Liu et al, 2012]. ICC in murine, nonhuman primate, and human GI tracts express ANO 1, a Ca ++ -activated Cl -channel which is encoded by the transmembrane protein Tmem 16a [Gomez-Pinilla et al, 2009;Hwang et al, 2009;Kashyap et al, 2011;Sanders et al, 2011;Blair et al, 2012b].…”

Section: Discussionmentioning

confidence: 93%

“…The organization of ICC in normal human colonic muscle has previously been studied by c-kit immunoreactivity [e.g. Vanderwinden et al, 1996;Hagger et al, 1998;Horisawa et al, 1998;Rømert and Mikkelsen, 1998;Torihashi et al, 1999;He et al, 2000;Mazzia et al, 2000;Vanderwinden et al, 2000aVanderwinden et al, , 2002Wedel et al, 2002;Pieri et al, 2008;Liu et al, 2012] as well as by electron microscopy [e.g. Faussone-Pellegrini et al, 1990a, b;Rumessen et al, 1993Rumessen et al, , 2009Torihashi et al, 1999;Gibbons et al, 2009].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Ultrastructure of Interstitial Cells in Subserosa of Human Colon

Rumessen

Vanderwinden

Hansen

et al. 2013

Cells Tissues Organs

View full text Add to dashboard Cite

We studied the ultrastructure of interstitial cells in the subserosal/adventitial layer in human colon. An interstitial cell type with an ultrastructure intermediate between fibroblast-like cells (FLC) and interstitial cells of Cajal was identified (IC-SS). IC-SS had thin and flattened branching processes, most densely arranged close to the longitudinal muscle cells. Caveolae, bundles of intermediate filaments and membrane-associated dense bands, often with a patchy basal lamina, were characteristic. Secretory organelles (granular endoplasmic reticulum, smooth endoplasmic reticulum, Golgi, coated vesicles) were prominent. The IC-SS ultrastructure was different from that of FLC in the longitudinal layer, which had no caveolae and fewer intermediate filaments. Peg-and-socket junctions between IC-SS and between IC-SS and muscle cells were present, and IC-SS processes had close, selective appositions to muscle cells. Gap junctions were not observed. Small nerve bundles were abundant, but close contacts (<100 nm) between IC-SS or muscle cells and nerves were inconspicuous. Close appositions between IC-SS and mast cells were present; close relations to macrophages were not observed. The myoid features of IC-SS are thus more pronounced in comparison with FLC of other locations in the gastrointestinal muscle. The organization and ultrastructure may suggest a regulatory nature of IC-SS on the colonic muscle layers.

show abstract

Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Ultrastructure of Interstitial Cells in Subserosa of Human Colon

Rumessen

Vanderwinden

Hansen

et al. 2013

Cells Tissues Organs

View full text Add to dashboard Cite

show abstract

“…Because more tissue information can potentially be seen with transparent specimens, the importance of optical clearing in deep-tissue microscopy has recently been highlighted in neuroscience as well as in the imaging community. Work is proceeding on developing different clearing reagents and to establish different target tissues, including the gut and brain, to help understand the 3-D features of tissue architectures [16][17][18]20].…”

Section: Discussionmentioning

confidence: 99%

“…To overcome the imaging hurdle, we previously developed a penetrative imaging method, based on preparation of transparent tissues (or 'optical clearing') [11,12], for 3-dimensional (3-D) imaging of the mouse pancreatic and intestinal microstructure and vasculature [13][14][15] and the human enteric nervous system [16,17]. Photon penetration in the tissue was improved by the process of optical clearing (i.e.…”

Section: Introductionmentioning

confidence: 99%

3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury

Chiu

Hua

et al. 2012

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis Sympathetic nerves influence islet hormone levels in the circulation. Insights into islet sympathetic innervation and its remodelling in diabetes may impact future therapeutics. However, standard immunohistochemistry and microtome-based microscopy cannot provide an integral view of the islet neurovascular complex. We prepared transparent islet specimens to investigate the spatial relationship between sympathetic nerves, blood vessels and islet cells in normal, streptozotocin-injected and non-obese diabetic mouse models. Methods Cardiac perfusion of fluorescent lectin was used to label pancreatic blood vessels. Tyrosine hydroxylase and nuclear staining were used to reveal islet sympathetic innervation and microstructure. Optical clearing (i.e. use of immersion solution to reduce scattering) was applied to enable 3-dimensional confocal microscopy of islets to visualise the sympathetic neurovascular complex in space. Results Unlike previously reported morphology, we observed perfusive intra-islet, perivascular sympathetic innervation, in addition to peri-islet contacts of sympathetic nerves with alpha cells and sympathetic fibres encircling the adjacent arterioles. The intra-islet axons became markedly prominent in streptozotocin-injected mice (2 weeks after injection). In non-obese diabetic mice, lymphocytic infiltration remodelled the peri-islet sympathetic axons in early insulitis. Conclusions/interpretation We have established an imaging approach to reveal the spatial features of mouse islet sympathetic innervation. The neurovascular complex and sympathetic nerve-alpha cell contact suggest that sympathetic nerves modulate islet hormone secretion through blood vessels, in addition to acting directly on alpha cells. In islet injuries, sympathetic nerves undergo different remodelling in response to different pathophysiological cues.

show abstract

“…To elucidate the activity of Schwann cells and pericytes in islet injury, we prepared transparent islet specimens by optical clearing [22][23][24][25] and combined vessel painting (perfusion of fluorescent lectin) with three-dimensional (3D) histology [26][27][28][29][30][31][32]. This allowed the identification of the spatial features of the GFAP + Schwann cells and NG2 + pericytes (note: although named as a neuron-'glial' antigen, the NG2 cell-surface chondroitin sulfate proteoglycan is highly expressed in the pancreatic/islet pericytes and has been used as a histological marker [5,33]) and their association with the islet lesion and vasculature [13,17,[34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Plasticity of Schwann cells and pericytes in response to islet injury in mice

et al. 2013

Self Cite

View full text Add to dashboard Cite

Aims/hypothesis Islet Schwann (glial) cells and pericytes are the microorgan's accessory cells positioned at the external and internal boundaries facing the exocrine pancreas and endothelium, respectively, adjacent to the endocrine cells. Plasticity of glial cells and pericytes is shown in the glial scar formation after injury to the central nervous system. It remains unclear whether similar reactive cellular responses occur in insulitis. We applied three-dimensional (3D) histology to perform qualitative and quantitative analyses of the islet Schwann cell network and pericytes in normal, streptozotocin-injected (positive control of gliosis) and NOD mouse models. Methods Vessel painting paired with immunostaining of mouse pancreatic tissue was used to reveal the islet Schwann cells and pericytes and their association with vasculature. Transparent islet specimens were prepared by optical clearing to facilitate 3D confocal microscopy for panoramic visualisation of the tissue networks.Results In-depth microscopy showed that the islet Schwann cell network extends from the peri-islet domain into the core. One week after streptozotocin injection, we observed intraislet perivascular gliosis and an increase in pericyte density. In early/moderate insulitis in the NOD mice, perilesional gliosis occurred at the front of the lymphocytic infiltration with atypical islet Schwann cell morphologies, including excessive branching and perivascular gliosis. Meanwhile, pericytes aggregated on the walls of the feeding arteriole at the peri-and intralesional domains with a marked increase in surface marker density. Conclusions/interpretationThe reactive cellular responses demonstrate plasticity and suggest a stop-gap mechanism consisting of the Schwann cells and pericytes in association with the islet lesion and vasculature when injury occurs.

show abstract

3-D illustration of network orientations of interstitial cells of Cajal subgroups in human colon as revealed by deep-tissue imaging with optical clearing

Cited by 26 publications

References 41 publications

Ultrastructure of Interstitial Cells in Subserosa of Human Colon

Ultrastructure of Interstitial Cells in Subserosa of Human Colon

3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury

Plasticity of Schwann cells and pericytes in response to islet injury in mice

Contact Info

Product

Resources

About