On the development of the Islets of Langerhans

Larsson, Lars‐Inge

doi:10.1002/(sici)1097-0029(19981115)43:4<284::aid-jemt2>3.0.co;2-0

Cited by 29 publications

(12 citation statements)

References 54 publications

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“…26 One possible explanation is that the remaining single cells are contributing to basal insulin expression, but are not increasing their insulin release in response to high-glucose media conditions, a finding consistent with other published studies. 27 In vivo, the development of mature islets begins as differentiated insulin þ cells aggregate to form insulin cell clusters, while separately formed clusters of glucagon cells, originating from multihormonal cells, 28 elongate and surround the insulin cell core. 28,29 Because very little cell migration is expected to occur in hydrogels utilized in this study, in vitro development of undifferentiated PDX-1 þ precursor cell clusters into islet-like structures within PEGCol hydrogels must proceed through a mechanism different from in vivo development.…”

Section: Discussionmentioning

confidence: 99%

“…27 In vivo, the development of mature islets begins as differentiated insulin þ cells aggregate to form insulin cell clusters, while separately formed clusters of glucagon cells, originating from multihormonal cells, 28 elongate and surround the insulin cell core. 28,29 Because very little cell migration is expected to occur in hydrogels utilized in this study, in vitro development of undifferentiated PDX-1 þ precursor cell clusters into islet-like structures within PEGCol hydrogels must proceed through a mechanism different from in vivo development. Previous studies demonstrated that induced clustering of adult pancreatic ductal epithelial cells enhanced b-cell dif- ferentiation and islet formation.…”

Section: Discussionmentioning

confidence: 99%

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Entrapped Collagen Type 1 Promotes Differentiation of Embryonic Pancreatic Precursor Cells into Glucose-Responsive β-Cells When Cultured in Three-Dimensional PEG Hydrogels

Mason

Arnold

Mahoney

2009

Tissue Engineering Part A

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Development of an alternative source of functional, transplantable beta-cells to replace or supplement cadaveric tissue is critical to the future success of islet cell transplantation therapy. Embryonic pancreatic precursor cells are desirable as a renewable source of beta-cells as they are both proliferative and inherently capable of pancreatic cell differentiation. We have previously shown that precursor cells undergo selective beta-cell differentiation when dissociated and photoencapsulated in a polyethylene glycol (PEG) hydrogel network; however, these cells remained immature and were not glucose responsive. Collagen type 1 supports mature cell viability and function in many cell types and we hypothesized that incorporating it within our gels may support differentiating beta-cells and facilitate beta-cell maturation. For these studies, collagen-1 was entrapped with dissociated pancreatic precursor cells in a PEG hydrogel matrix (PEGCol) with the following key findings: (1) mature, glucose-responsive, islet-like structures differentiated from spontaneously forming precursor cell clusters in PEGCol, but not unmodified PEG, hydrogels; (2) a balance existed between providing sufficient collagen-1 signaling to support precursor cell development and providing an overabundance of adhesive sites allowing contaminating mesenchymal cells to thrive' and (3) mechanical stability provided by the PEG hydrogel platform is important for successful precursor cell culture, as PEGCol hydrogels encourage glucose responsiveness and high-insulin gene expression, while pure collagen gel cultures, with the same collagen concentration, have negligible insulin gene expression. These results indicate that PEGCol hydrogels are a useful culture platform to promote differentiation of a glucose-responsive beta-cell population from dissociated precursor cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Entrapped Collagen Type 1 Promotes Differentiation of Embryonic Pancreatic Precursor Cells into Glucose-Responsive β-Cells When Cultured in Three-Dimensional PEG Hydrogels

Mason

Arnold

Mahoney

2009

Tissue Engineering Part A

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“…A specific hierarchy in the appearance of these hormones has been demonstrated. The glucagon-producing α-cells appear very early during development [at embryonic day 9.5(E9.5)] [2,3]. On the following day (E10.5), insulin-producing cells can be detected.…”

Section: Introductionmentioning

confidence: 99%

“…On the following day (E10.5), insulin-producing cells can be detected. Cells producing somatostatin and PP appear only at E15.5 and at birth, respectively [2,3]. Indeed, the development of pancreas appears to be a very complicated event.…”

Section: Introductionmentioning

confidence: 99%

Neurogenin3 triggers beta-cell differentiation of retinoic acid-derived endoderm cells

Vetere

Marsich

Piazza

et al. 2003

Biochemical Journal

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Neurogenin3 is a member of the basic helix-loop-helix ('bHLH') family of transcription factors. It plays a crucial role in the commitment of embryonic endoderm into the pancreatic differentiation programme. This factor is considered to act upstream of a cascade of other transcription factors, leading to the fully differentiated endocrine phenotype. Direct observation of the sequential activation of these factors starting from Neurogenin3 had never been demonstrated. By using retinoic acid-derived-endoderm F9 cells as a model, the present study indicates that the ectopic expression of Neurogenin3 is able to start the differentiation pathway of endocrine pancreas. Neurogenin3 triggers the expression of several pancreatic transcription factors following a well defined temporal activation sequence. By reverse transcriptase PCR, immunohistochemistry and RIA, it is shown that stable transfected cells are able to form embryod bodies that produce insulin in response to glucose stimulation. This is the first report of a differentiation event induced by the ectopic expression of a transcription factor in embryonic pluripotent stem cells.

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“…During development, there are some contrasting findings regarding the presence of PP family peptides in the endocrine pancreas of early mouse embryos. It seems that precursor cells coexpress insulin and glucagon (for a review see Larsson, 1998). In these cells PP‐IR (Herrera et al ,1991; Wolfe‐Coote et al, 1998), NPY‐IR (Teitelman et al, 1993), and PYY‐IR (Upchurch et al, 1994; Jackerott et al, 1996) were reported.…”

mentioning

confidence: 99%

NPY immunoreactivity in endocrine cells of duck pancreas: An ontogenetic study

2000

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In the literature, neuropeptide Y (NPY) has been described in the brain and peripheral nerves. More recently, it has also been detected in endocrine cells of hamster, embryonic mouse, and rat pancreas. However, the presence of NPY in avian embryos and the possible colocalization of this peptide with the other pancreatic hormones have not been reported previously. In this study, NPY presence was studied by immunocytochemical methods in the endocrine pancreas of domestic duck during pre- and postnatal development. NPY immunoreactivity (IR) was detected in embryos and adult animals. Around hatching the intensity of IR in endocrine cells decreased. Double immunohistochemical staining revealed that: 1) NPY-IR is extensively colocalized in small and mixed islets with insulin-IR both in embryos and in adults; and 2) in early embryos NPY-IR occasionally colocalized with glucagon and somatostatin. In early embryos, the colocalization of NPY-IR with several pancreatic hormones could be related to the presence of multi-hormonal progenitor cells. The close relation between insulin and NPY, both in embryos and adults, led us to hypothesize a key role for NPY on insulin cells of duck pancreas.

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On the development of the Islets of Langerhans

Cited by 29 publications

References 54 publications

Entrapped Collagen Type 1 Promotes Differentiation of Embryonic Pancreatic Precursor Cells into Glucose-Responsive β-Cells When Cultured in Three-Dimensional PEG Hydrogels

Entrapped Collagen Type 1 Promotes Differentiation of Embryonic Pancreatic Precursor Cells into Glucose-Responsive β-Cells When Cultured in Three-Dimensional PEG Hydrogels

Neurogenin3 triggers beta-cell differentiation of retinoic acid-derived endoderm cells

NPY immunoreactivity in endocrine cells of duck pancreas: An ontogenetic study

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