Three-dimensional islet graft histology: panoramic imaging of neural plasticity in sympathetic reinnervation of transplanted islets under the kidney capsule

Juang, Jyuhn‐Huarng; Peng, Shih-Jung; Kuo, Chun‐Yan; Tang, Shiue–Cheng

doi:10.1152/ajpendo.00515.2013

Cited by 31 publications

(27 citation statements)

References 42 publications

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“…Avizo's noise filtering algorithms were applied for background noise reduction. Signal tracing and feature extraction were performed by the Label Field function of Avizo to estimate the tissue volume via the occupied voxels [26]. Image stacks presented in ESM Videos were recorded using the Movie Maker function of Avizo with increase in display time in association with the depth of the optical section.…”

Section: Methodsmentioning

confidence: 99%

Human pancreatic neuro-insular network in health and fatty infiltration

et al. 2017

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Aims/hypothesis Identification of a pancreatic neuro-insular network in mice suggests that a similar integration of islets and nerves may be present in the human pancreas. To characterise the neuro-insular network and the intra-pancreatic ganglia in a clinically related setting, we examined human pancreases in health and with fatty infiltration via 3-dimensional (3D) histology and compared the human pancreatic microenvironment with its counterpart in mice. Methods Human pancreatic specimens from individuals with normal BMI, high BMI (≥ 25) and type 2 diabetes were used to investigate the neuro-insular network. Transparent specimens were prepared by tissue clearing for transmitted light and deeptissue fluorescence imaging to simultaneously visualise infiltrated adipocytes, islets and neurovascular networks. Results High-definition images of human islets reveal that both the sympathetic and parasympathetic nerves enter the islet core and reside in the immediate microenvironment of islet cells. Around the islets, the neuro-insular network is visualised with 3D histology to identify the intra-pancreatic ganglia (peri-lobular and intra-parenchymal ganglia) and the islet-ganglionic association. In humans, but not in mice, pancreatic fatty infiltration (BMI dependent) features adipocytes infiltrating into the parenchyma and accumulating in the perilobular space, in which the peri-lobular ganglia also reside. We identified the formation of adipose-ganglionic complexes in the peri-lobular space and enlargement of ganglia around adipocytes. In the specimen from the individual with type 2 diabetes, an increase in the number of nerve projections from the intra-parenchymal ganglia is associated with severe fatty infiltration. Conclusions/interpretation We present new perspectives of human pancreas and islet innervation via 3D histology. Our results strongly suggest that fatty infiltration in the human pancreas creates a neurotrophic microenvironment and promotes remodelling of pancreatic innervation.

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Section: Methodsmentioning

confidence: 99%

Human pancreatic neuro-insular network in health and fatty infiltration

et al. 2017

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“…Avizo 6.2 image reconstruction software (VSG, Burlington, MA; operated with a Dell T7500 workstation), Zen software (Carl Zeiss), and LSM510 software (Carl Zeiss) were used for projection, signal segmentation, noise reduction, and analysis of confocal images. Quantitation of signal (CK19, NG2, and GFAP) density in an image stack is illustrated in (25). Briefly, to estimate density, feature extraction and image segmentation were first performed using the Label Field function in Avizo to collect voxels of lesion (or normal area) and those of CK19, NG2, or GFAP signals.…”

Section: Methodsmentioning

confidence: 99%

PanIN-associated pericyte, glial, and islet remodeling in mice revealed by 3D pancreatic duct lesion histology

Lin

Peng

Shen

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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Pericytes and glial cells are accessory cells of neurovascular networks, which have been reported to participate in scar formation after tissue injury. However, it remains unclear whether similar reactive cellular responses occur in pancreatic intraepithelial neoplasia (PanIN). In this study we developed three-dimensional (3D) duct lesion histology to investigate PanIN and the associated pericyte, glial, and islet remodeling. Transparent mouse pancreata with a Kras G12D mutation were used to develop 3D duct lesion histology. Deep-tissue, tile-scanning microscopy was performed to generate panoramic views of the diseased pancreas for global examination of early stage and advanced duct lesion formation. Fluorescence signals of ductal and neurovascular networks were simultaneously detected to reveal associated remodeling. Significantly, in Kras G12D -mutant mice, when the low-grade PanINs emerge, duct lesions appear as epithelial buds with perilesional pericyte and glial activation. When PanINs occur in large scale (induced by cerulein injections to the mutant mice), the 3D image data identifies 1) aggregation of PanINs in clusters in space; 2) overexpression of the pericyte marker NG2 in the PanIN microenvironment; and 3) epithelial in-growth to islets, forming the PanIN-islet complexes. Particularly, the PanIN-islet complexes associate with proliferating epithelial and stromal cells and receive substantial neurovascular supplies, making them landmarks in the atrophic lobe. Overall, perilesional pericyte and glial activation and formation of the PanIN-islet complex underline cellular heterogeneity in the duct lesion microenvironment. The results also illustrate the advantage of using 3D histology to reveal previously unknown details of neurovascular and endocrine links to the disease. 3D histology; Kras G12D mutation; optical clearing; pancreatic intraepithelial neoplasia; PanIN-islet complex

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“…In rodents, Juang et al . (), who also used TH, demonstrated sympathetic innervation of islet grafted mouse, resembling innervation in the pancreas in situ . Slack () reported that innervation with ganglion cells and unmyelinated fibers starts at the 50 somite stage and embryonic vascularization begins at 14 days in mice.…”

Section: Discussionmentioning

confidence: 91%

Isolation and Characterization of Pancreatic Canine Fetal Cells at the Final Stage of Gestation

Orechio

Fratini

Carreira

et al. 2018

The Anatomical Record

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The incidence of diabetes mellitus in dogs is increasing in recent years, mainly because of genetic and/or environmental factors, including endocrine disorders (like in humans); failure of suitable control of blood sugar levels, which triggers hyperglycemia; glycosuria and weight loss, which demands the development of innovative treatments to cure or treat this complex disease in dogs. The present study established for the first time a protocol to obtain and characterize cells derived from pancreas of canine fetuses. Those fetuses do not have a defined breed and were at the final stage of gestation. The protocol aims to provide morphological data to enable future applications of these cells for therapeutic approaches. In cell culture, pancreatic cells showed a fibroblastlike appearance with a mono-layered growth pattern and were not tumorigenic. They exhibited a positive expression for the pluripotent proliferation markers NANOG and PCNA and expressed PDX1, a transcription factor that is important for activation of the insulin gene promoter. In addition, Tyrosine Hydroxylase-positive (TH+) sympathetic nerve fibers were identified. Histologically, the pancreatic epithelium was developed, pancreatic glands in the fetuses were like those in the parenchyma of postconception dogs and pancreatic islets were unevenly distributed and organized in small clusters along the glands close to the vasculature. Staining with dithizone indicated the presence of insulin in the cells. A large number of beta cells were confirmed by immunofluorescence. In conclusion, the canine fetal pancreas cells could be an alternative and adequate source of cell lineages for stem

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Three-dimensional islet graft histology: panoramic imaging of neural plasticity in sympathetic reinnervation of transplanted islets under the kidney capsule

Cited by 31 publications

References 42 publications

Human pancreatic neuro-insular network in health and fatty infiltration

Human pancreatic neuro-insular network in health and fatty infiltration

PanIN-associated pericyte, glial, and islet remodeling in mice revealed by 3D pancreatic duct lesion histology

Isolation and Characterization of Pancreatic Canine Fetal Cells at the Final Stage of Gestation

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