Changes in the Mouse Exocrine Pancreas after Pancreatic Duct Ligation: A Qualitative and Quantitative Histological Study.

Watanabe, Satoshi; Abe, Kazuhiro; Anbo, Yoshiyasu; Katoh, Hiroyuki

doi:10.1679/aohc.58.365

Cited by 77 publications

(57 citation statements)

References 23 publications

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“…These results are in contrast to other mouse models [6,7] and even pig models with simple ligation of the main pancreatic duct close to the duodenum -likely because of possible accessory drainages- [19,28,29] in which some regeneration of acinar tissue occurred. Although, the model results in the appearance of ADM in the short term RFAT group, as described after PDL [12,16,30], we have demonstrated the reduction of the ADM area in the long-term group compared to the short-term group (from 56% to 21% of the cross-sectional area), in spite of the growth of the animal. To our knowledge, this issue has not been demonstrated before and may consistently show that ADM may disappear after a reliable obstruction of the pancreatic duct in healthy conditions, as demonstrated by a 3-fold increase in mean preoperative weight.…”

Section: Discussionsupporting

confidence: 60%

“…Since complete duct occlusion should prevent duct cells regenerating into acinar cells after PDL [16] and some morphometric results could have been biased by including injured pancreas [7,11], the present study implemented six key differences from conventional PDL mouse models in order to ensure efficient and reliable pancreatic duct occlusion and accurate evaluation:…”

Section: Discussionmentioning

confidence: 99%

“…It is also important to highlight that an automatic acquisition of complete pancreatic sections of both Ck7 and insulin expression, including the analysis of up to 1,000 histological photographs per animal was considered to represent the entire pancreas volume. And this analysis is in clear contrast to other manual volumetry calculations which include only selected areas of the preparations [8,16]. Finally, we used a new PDL system based on RF-assisted transection (RFAT) which has previously been shown to avoid pancreatic fistula formation [22,27].…”

Section: Discussionmentioning

confidence: 99%

“…Recent results from PDL in mouse models have shown that some acinar cells can escape death [7] and that acinar compartment can regenerate in a long-term evolution after PDL (over 6 months), probably by restoration of pancreatic drainage [6]. Ever since the first studies on PDL in mouse models it has been said that this technique is difficult because its unique anatomy hampers the results [15,16]. The mouse pancreas is usually poorly defined and consists of three lobes (gastric, splenic and duodenal) which drain their juices via individual ducts only 150 µm in diameter [16,17] and there are also frequent variations in this drainage.…”

Section: Introductionmentioning

confidence: 99%

“…Ever since the first studies on PDL in mouse models it has been said that this technique is difficult because its unique anatomy hampers the results [15,16]. The mouse pancreas is usually poorly defined and consists of three lobes (gastric, splenic and duodenal) which drain their juices via individual ducts only 150 µm in diameter [16,17] and there are also frequent variations in this drainage. Researchers usually ligate the splenic lobe from the rest of the pancreas, however this technique is challenging due to the small diameter of the pancreatic duct and usually requires the help of a microscope for the dissection.…”

Section: Introductionmentioning

confidence: 99%

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Long-term evolution of acinar-to-ductal metaplasia and β-cell mass after radiofrequency-assisted transection of the pancreas in a controlled large animal model

Quesada¹,

Andaluz

Cáceres

et al. 2016

Pancreatology

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ABSTRACT:Background: Pancreatic duct ligation (PDL) has been used as a model of chronic pancreatitis and as a model to increase β-cell mass. However, studies in mice have demonstrated acinar regeneration after PDL, questioning the long-term validity of the model. We aim to elucidate whether RF-assisted transection (RFAT) of the main pancreatic duct is a reliable PDL model, both in short (ST, 1-month) and long-term (LT, 6-months) follow-ups. Methods: Eleven pigs were subjected to RFAT. Biochemical (serum/peripancreatic amylase and glucose) and histological changes (including a semiautomatic morphometric study of over 1000 images/pancreas and IHC analysis) were evaluated after ST or LT follow-up and also in fresh pancreas specimens that were used as controls for 1 (n=4) and 6 months (n=6). Results: The distal pancreas in the ST was characterized by areas of acinar-to-ductal metaplasia (56%) which were significantly reduced at LT (21%) by fibrotic replacement and adipose tissue. The endocrine mass showed a normal increase. Conclusion: RFAT in the pig seems to be an appropriate PDL model without restoration of pancreatic drainage or reduction of endocrine mass.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Long-term evolution of acinar-to-ductal metaplasia and β-cell mass after radiofrequency-assisted transection of the pancreas in a controlled large animal model

Quesada¹,

Andaluz

Cáceres

et al. 2016

Pancreatology

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Pancreatic Blood Flow with Special Emphasis on Blood Perfusion of the Islets of Langerhans

Jansson

Carlsson

2019

Comprehensive Physiology

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The pancreatic islets are more richly vascularized than the exocrine pancreas, and possess a 5‐ to 10‐fold higher basal and stimulated blood flow, which is separately regulated. This is reflected in the vascular anatomy of the pancreas where islets have separate arterioles. There is also an insulo‐acinar portal system, where numerous venules connect each islet to the acinar capillaries. Both islets and acini possess strong metabolic regulation of their blood perfusion. Of particular importance, especially in the islets, is adenosine and ATP/ADP. Basal and stimulated blood flow is modified by local endothelial mediators, the nervous system as well as gastrointestinal hormones. Normally the responses to the nervous system, especially the parasympathetic and sympathetic nerves, are fairly similar in endocrine and exocrine parts. The islets seem to be more sensitive to the effects of endothelial mediators, especially nitric oxide, which is a permissive factor to maintain the high basal islet blood flow. The gastrointestinal hormones with pancreatic effects mainly influence the exocrine pancreatic blood flow, whereas islets are less affected. A notable exception is incretin hormones and adipokines, which preferentially affect islet vasculature. Islet hormones can influence both exocrine and endocrine blood vessels, and these complex effects are discussed. Secondary changes in pancreatic and islet blood flow occur during several conditions. To what extent changes in blood perfusion may affect the pathogenesis of pancreatic diseases is discussed. Both type 2 diabetes mellitus and acute pancreatitis are conditions where we think there is evidence that blood flow may contribute to disease manifestations. © 2019 American Physiological Society. Compr Physiol 9:799‐837, 2019.

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Ductal obstruction promotes formation of preneoplastic lesions from the pancreatic ductal compartment

Cheng

Zhang

Jian

et al. 2018

Intl Journal of Cancer

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Pancreatitis is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC). Previous studies in mice have demonstrated that pancreatitis contributes to oncogenic Kras‐driven carcinogenesis, probably initiated in acinar cells; however, oncogenic Kras alone or in combination with caerulein‐induced pancreatitis is not sufficient in initiating PDAC from the ductal compartment. We thus introduced ductal obstruction – which induces a more severe form of pancreatitis – by pancreatic ductal ligation in mice harbouring oncogenic Kras. This induced a particular phenotype with highly proliferative nonmucinous cells with nuclear atypia. Around these lesions, there was a significant proliferation of activated fibroblasts and infiltration of immune cells, corroborating the pathological features of preneoplastic lesions. Lineage‐tracing experiments revealed that these preneoplastic cells derived from two distinctive cellular sources: acinar and ductal cells. Phenotypic characterisation revealed that the duct‐derived preneoplastic lesions show a high proliferative potential with persistent activation of tumour‐promoting inflammatory pathways while the acinar‐derived ones were less proliferative with persistent p53 activation. Furthermore, the duct‐derived preneoplastic cells have a particularly high nuclear‐to‐cytoplasmic ratio. These data demonstrate that ductal obstruction promotes preneoplastic lesion formation from the pancreatic ductal compartment.

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Changes in the Mouse Exocrine Pancreas after Pancreatic Duct Ligation: A Qualitative and Quantitative Histological Study.

Cited by 77 publications

References 23 publications

Long-term evolution of acinar-to-ductal metaplasia and β-cell mass after radiofrequency-assisted transection of the pancreas in a controlled large animal model

Long-term evolution of acinar-to-ductal metaplasia and β-cell mass after radiofrequency-assisted transection of the pancreas in a controlled large animal model

Pancreatic Blood Flow with Special Emphasis on Blood Perfusion of the Islets of Langerhans

Ductal obstruction promotes formation of preneoplastic lesions from the pancreatic ductal compartment

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