Pancreatic acinar cell fate relies on system x to prevent ferroptosis during stress.

Acinar cell dedifferentiation is one of the most notable features of acute and chronic pancreatitis. It can also be the initial step that facilitates pancreatic cancer development. In the present study, we further decipher the precise mechanisms and regulation using primary human cells and murine experimental models.

Do cancer centres and palliative care wards routinely measure patients' quality of life? An international cross-sectional survey study.

Purpose: Routinely assessing quality of life (QoL) of patients with cancer is crucial for improving patient-centred cancer care. However, little is known about whether or how cancer centres assess QoL for clinical practice or for research purposes. Therefore, our study aimed to investigate if QoL data is collected and if so, how and for what purposes.

On the Origin of Pancreatic Cancer: Molecular Tumor Subtypes in Perspective of Exocrine Cell Plasticity.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating type of cancer. While many studies have shed light into the pathobiology of PDAC, the nature of PDAC's cell of origin remains under debate. Studies in adult pancreatic tissue have unveiled a remarkable exocrine cell plasticity including transitional states, mostly exemplified by acinar to ductal cell metaplasia, but also with recent evidence hinting at duct to basal cell transitions.

MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions.

Maintenance of the pancreatic acinar cell phenotype suppresses tumor formation. Hence, repetitive acute or chronic pancreatitis, stress conditions in which the acinar cells dedifferentiate, predispose for cancer formation in the pancreas. Dedifferentiated acinar cells acquire a large panel of duct cell-specific markers.

Adult human pancreatic acinar cells dedifferentiate into an embryonic progenitor-like state in 3D suspension culture.

Human pancreatic exocrine cells were cultured in 3D suspension and formed pancreatospheres composed of acinar-derived and duct-like cells. We investigated, up to 6 days, the fate of human pancreatic acinar cells using fluorescein-conjugated Ulex Europaeus Agglutinin 1 lectin, a previously published acinar-specific non-genetic lineage tracing strategy. At day 4, fluorescence-activated cell sort for the intracellularly incorporated FITC-conjugated UEA1 lectin and the duct-specific CA19.

Acinar cells in the neonatal pancreas grow by self-duplication and not by neogenesis from duct cells.

Pancreatic acinar cells secrete digestive enzymes necessary for nutrient digestion in the intestine. They are considered the initiating cell type of pancreatic cancer and are endowed with differentiation plasticity that has been harnessed to regenerate endocrine beta cells. However, there is still uncertainty about the mechanisms of acinar cell formation during the dynamic period of early postnatal development.

Acinar phenotype is preserved in human exocrine pancreas cells cultured at low temperature: implications for lineage-tracing of β-cell neogenesis.

The regenerative medicine field is expanding with great successes in laboratory and preclinical settings. Pancreatic acinar cells in diabetic mice were recently converted into β-cells by treatment with ciliary neurotrophic factor (CNTF) and epidermal growth factor (EGF). This suggests that human acinar cells might become a cornerstone for diabetes cell therapy in the future, if they can also be converted into glucose-responsive insulin-producing cells.

Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population.

Tumor-associated macrophages (TAM) are exposed to multiple microenvironmental cues in tumors, which collaborate to endow these cells with protumoral activities. Hypoxia, caused by an imbalance in oxygen supply and demand because of a poorly organized vasculature, is often a prominent feature in solid tumors. However, to what extent tumor hypoxia regulates the TAM phenotype in vivo is unknown.

The use of stem cells for pancreatic regeneration in diabetes mellitus.

The endocrine pancreas represents an interesting arena for regenerative medicine and cell therapeutics. One of the major pancreatic diseases, diabetes mellitus is a metabolic disorder caused by having an insufficient number of insulin-producing β cells. Replenishment of β cells by cell transplantation can restore normal metabolic control.

Suppression of epithelial-to-mesenchymal transitioning enhances ex vivo reprogramming of human exocrine pancreatic tissue toward functional insulin-producing β-like cells.

Because of the lack of tissue available for islet transplantation, new sources of β-cells have been sought for the treatment of type 1 diabetes. The aim of this study was to determine whether the human exocrine-enriched fraction from the islet isolation procedure could be reprogrammed to provide additional islet tissue for transplantation. The exocrine-enriched cells rapidly dedifferentiated in culture and grew as a mesenchymal monolayer.

Gene delivery to pancreatic exocrine cells in vivo and in vitro.

Background: Effective gene transfer to the pancreas or to pancreatic cells has remained elusive although it is essential for studies of genetic lineage tracing and modulation of gene expression. Different transduction methods and viral vectors were tested in vitro and in vivo, in rat and mouse pancreas.

Results: For in vitro transfection/transduction of rat exocrine cells lipofection reagents, adenoviral vectors, and Mokola- and VSV-G pseudotyped lentiviral vectors were used.

Genetic lineage tracing of beta cell neogenesis.

Genetic lineage tracing is an invaluable tool to demonstrate and measure neogenesis of beta cells from putative precursor cells. Cre-Lox recombination technology can be used for indelible labeling of a cohort of cells and following the fate of these cells and their progeny in animal models. Here, the combination is described of beta-galactosidase enzymatic staining with immunohistochemical staining to demonstrate labeled cells.

Lineage tracing of pancreatic stem cells and beta cell regeneration.

Restoring a functional β cell mass in diabetes patients by β cell transplantation or stimulation of β cell regeneration are promising approaches. It requires knowledge on the mechanisms of β cell neogenesis, an issue that is still quite controversial. Postnatal islet regeneration may or may not depend on an influx of new islet cells from adult progenitors.

Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophages.

Tumor-associated macrophages (TAM) are an important component of the tumor stroma and exert several tumor-promoting activities. Strongly pro-angiogenic TAMs that reside in hypoxic tumor areas highly express macrophage mannose receptor (MMR, CD206). In this study, we targeted MMR+ TAMs using nanobodies, which are single-domain antigen-binding fragments derived from Camelidae heavy-chain antibodies.

Lineage tracing evidence for transdifferentiation of acinar to duct cells and plasticity of human pancreas.

Background & Aims: Animal studies have indicated that pancreatic exocrine acinar cells have phenotypic plasticity. In rodents, acinar cells can differentiate into ductal precursors that can be converted to pancreatic ductal adenocarcinoma or insulin-producing endocrine cells. However, little is known about human acinar cell plasticity.

The quest for tissue stem cells in the pancreas and other organs, and their application in beta-cell replacement.

Adult stem cell research has drawn a lot of attention by many researchers, due to its medical hope of cell replacement or regenerative therapy for diabetes patients. Despite the many research efforts to date, there is no consensus on the existence of stem cells in adult pancreas. Genetic lineage tracing experiments have put into serious doubt whether β-cell neogenesis from stem/progenitor cells takes place postnatally.

Pancreatic exocrine duct cells give rise to insulin-producing beta cells during embryogenesis but not after birth.

A longstanding unsettled question is whether pancreatic beta cells originate from exocrine duct cells. We have now used genetic labeling to fate map embryonic and adult pancreatic duct cells. We show that Hnf1beta+ cells of the trunk compartment of the early branching pancreas are precursors of acinar, duct, and endocrine lineages.