Islet formation in mice and men: lessons for the generation of functional insulin-producing β-cells from human pluripotent stem cells

Nair, Gopika; Hebrok, Matthias

doi:10.1016/j.gde.2015.03.004

Cited by 96 publications

(70 citation statements)

References 69 publications

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“…The spatio-temporal distribution of various structural forms of endocrine pancreas in general coincides with what has been described in the literature [8,40,41,44,48,51,57]. However, the data obtained in our study allowed us to clarify the main stages of the morphogenesis of the endocrine part of the pancreas during prenatal human development.…”

Section: Prenatal Development Of the Human Pancreassupporting

confidence: 88%

Ontogeny of the Human Pancreas

Proshchina¹,

Krivova²,

Гуревич³

et al. 2019

Comparative Endocrinology of Animals

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Pancreatic disorders are the most common pathologies in humans worldwide. Detailed information on pancreatic cytoarchitecture, vascularisation, innervation, morphogenesis, and cell differentiation is required for the development of new approaches to the treatment of these diseases. Currently, the majority of studies on pancreas development are performed on experimental animals (mainly rodents). Studies on human pancreatic prenatal development are restricted in number by ethical constraints and some technical difficulties. However, interspecies differences in pancreatic structure and development are considerable. Therefore, data obtained in experiments on animals and cell cultures must be supplemented with information obtained directly from human pancreatic autopsies. In this chapter, we summarise our previous results and the literature data on human pancreatic ontogeny. Special attention has been paid to the endocrine pancreas, which undergoes morphogenetic restructuring during human development. Several forms of structural organisation of the endocrine pancreas (single endocrine cells, small clusters of endocrine cells, mantle, bipolar, and mosaic islets) gradually appear during development. It is important that this restructuring is accompanied by changes in the ratio of pancreatic endocrine cells. The mechanisms of these changes are still unclear. The difficulties in identifying progenitor cells and tracking cell differentiation are the main problems associated with this issue.

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Section: Prenatal Development Of the Human Pancreassupporting

confidence: 88%

Ontogeny of the Human Pancreas

Proshchina¹,

Krivova²,

Гуревич³

et al. 2019

Comparative Endocrinology of Animals

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“…The onset of NKX2‐2 expression downstream of endocrine commitment in humans is supported by a recent study using human pluripotent stem cells to interrogate endocrine specification . Other transcription factors also showed delayed expression and resolution into distinct compartments of the developing human pancreas compared to the mouse and has recently been reviewed elsewhere …”

Section: The Role Of Neurog3 In Human Endocrine Pancreas Developmentmentioning

confidence: 86%

Revisiting the immunocytochemical detection of Neurogenin 3 expression in mouse and man

Honoré

Rescan

Hald

et al. 2016

Diabetes Obesity Metabolism

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).During embryonic development, endocrine cells of the pancreas are specified from multipotent progenitors. The transcription factor Neurogenin 3 (NEUROG3) is critical for this development and it has been shown that all endocrine cells of the pancreas arise from endocrine progenitors expressing NEUROG3. A thorough understanding of the role of NEUROG3 during development, directed differentiation of pluripotent stem cells and in models of cellular reprogramming, will guide future efforts directed at finding novel sources of β-cells for cell replacement therapies. In this article, we review the expression and function of NEUROG3 in both mouse and human and present the further characterization of a monoclonal antibody directed against NEUROG3. This antibody has been previously been used for detection of both mouse and human NEUROG3. However, our results suggest that the epitope recognized by this antibody is specific to mouse NEUROG3. Thus, we have also generated a monoclonal antibody specifically recognizing human NEUROG3 and present the characterization of this antibody here.Together, these antibodies will provide useful tools for future studies of NEUROG3 expression, and the data presented in this article suggest that recently described expression patterns of NEUROG3 in human foetal and adult pancreas should be re-examined. 1 Lessons from developmental biology have greatly aided advances in both of these approaches, but it has become evident that we still lack a complete understanding of the mechanisms involved in the commitment to the endocrine lineage and the specification of the individual endocrine cell types of the pancreas.In this article, we review the expression of the basic helix-loophelix transcription factor Neurogenin 3 (NEUROG3) and discuss its role in the endocrine specification during pancreas development and reprogramming of adult non-endocrine cells to β-cells. We also present a more extensive characterization of a monoclonal antibody (F25A1B3) raised against mouse NEUROG3 that we have previously developed (Figure 1). 2 This antibody was raised against mouse NEU-ROG3 but has also been used in several studies of human NEUROG3.Our data suggest that the specificity of this antibody is primarily directed towards mouse NEUROG3 and hence we also present the

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“…Unfortunately, this has not yet proved to be the case in human beings. Another approach for production of cells is to differentiate human induced pluripotent stem cells (iPSCs) into insulin-secreting beta cells [29,30]. If allogenic iPSCs are used, these, too, will require encapsulation and/or immunomodulation, as is the case for hESCs.…”

Section: Stem Cellsmentioning

confidence: 99%

Hope vs hype: where are we in type 1 diabetes?

Skyler

2017

Diabetologia

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Much progress has been made in type 1 diabetes research. Biological replacement of islet function has been achieved with pancreas transplantation and with islet transplantation. In the future, human embryonic stem cells and/or induced pluripotent stem cells may offer a potentially unlimited source of cells for islet replacement. Another potential strategy is to induce robust beta cell replication so that regeneration of islets can be achieved. Immune interventions are being studied with the hope of arresting the type 1 diabetes disease process to either prevent the disease or help preserve beta cell function. Mechanical replacement of islet cell function involves the use of glucose sensor-controlled insulin infusion systems. As all of these avenues are pursued, headlines often overstate the case, thus hyping any given advance, which provides enormous hope for patients and families seeking a cure for type 1 diabetes. Often, however, it is an animal study or a pilot trial that is being described. The reality is that translation to successful trials in human beings may not be readily achievable. This article discusses both the hype and the hopes in type 1 diabetes research.

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Islet formation in mice and men: lessons for the generation of functional insulin-producing β-cells from human pluripotent stem cells

Cited by 96 publications

References 69 publications

Ontogeny of the Human Pancreas

Ontogeny of the Human Pancreas

Revisiting the immunocytochemical detection of Neurogenin 3 expression in mouse and man

Hope vs hype: where are we in type 1 diabetes?

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