Plasticity and Dedifferentiation within the Pancreas: Development, Homeostasis, and Disease

Puri, Sapna; Folias, Alexandra E.; Hebrok, Matthias

doi:10.1016/j.stem.2014.11.001

Cited by 145 publications

(146 citation statements)

References 120 publications

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“…The mechanisms underlying cell-specific dedifferentiation have been indicated to be critical in developmental biology, 43 regenerative medicine, 44 and tumorigenesis. 45 Myofibroblast differentiation was previously considered irreversible.…”

Section: Role Of Dedifferentiation In Removing Myofibroblastsmentioning

confidence: 99%

Mechanisms of Lung Fibrosis Resolution

Glasser

Hagood

Wong

et al. 2016

The American Journal of Pathology

112

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Section: Role Of Dedifferentiation In Removing Myofibroblastsmentioning

confidence: 99%

Mechanisms of Lung Fibrosis Resolution

Glasser

Hagood

Wong

et al. 2016

The American Journal of Pathology

112

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“…To the neuroscientist, the pancreas can seem like a highly plastic organ whose cells are able to undergo vast changes in the context of homeostatic control and regeneration (1)(2)(3)(4). Such plasticity in the adult brain is exhibited only by endogenous neural stem cell (NSC) populations.…”

mentioning

confidence: 99%

“…Plasticity in the pancreas is demonstrated by multiple examples of trans-and dedifferentiation among various cell types reported; these have been experimentally induced, whether by pharmacological or genetic manipulation or by the implementation of damage and regeneration models (1,(6)(7)(8)(9)(10)(11)(12). An impressive amount of work has been done identifying the molecular mechanisms that control this plasticity.…”

mentioning

confidence: 99%

“…An impressive amount of work has been done identifying the molecular mechanisms that control this plasticity. The patterns that emerge indicate that a variety of signaling molecules and transcription factors act during development to both suppress and induce fates as well as to maintain proper function of the adult cell types, including the Notch and hedgehog pathways and a number of transcription factors, including pancreatic and duodenal homeobox 1 (Pdx1), neurogenin 3 (Ngn3), and the hairy and enhancer of split-1 (Hes/Hey) family (1,.…”

mentioning

confidence: 99%

“…First, we discuss specific aspects of pancreatic development on which light can be shed by our emerging understanding of noncanonical signaling in NSCs. We do not aim to provide a comprehensive review of the developmental processes of the pancreas because this has been meticulously done elsewhere (1)(2)(3)(4).…”

mentioning

confidence: 99%

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Endocrine Pancreas Development and Regeneration: Noncanonical Ideas From Neural Stem Cell Biology

et al. 2016

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Loss of insulin-producing pancreatic islet β-cells is a hallmark of type 1 diabetes. Several experimental paradigms demonstrate that these cells can, in principle, be regenerated from multiple endogenous sources using signaling pathways that are also used during pancreas development. A thorough understanding of these pathways will provide improved opportunities for therapeutic intervention. It is now appreciated that signaling pathways should not be seen as “on” or “off” but that the degree of activity may result in wildly different cellular outcomes. In addition to the degree of operation of a signaling pathway, noncanonical branches also play important roles. Thus, a pathway, once considered as “off” or “low” may actually be highly operational but may be using noncanonical branches. Such branches are only now revealing themselves as new tools to assay them are being generated. A formidable source of noncanonical signal transduction concepts is neural stem cells because these cells appear to have acquired unusual signaling interpretations to allow them to maintain their unique dual properties (self-renewal and multipotency). We discuss how such findings from the neural field can provide a blueprint for the identification of new molecular mechanisms regulating pancreatic biology, with a focus on Notch, Hes/Hey, and hedgehog pathways.

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Co‐microencapsulation of human umbilical cord‐derived mesenchymal stem and pancreatic islet‐derived insulin producing cells in experimental type 1 diabetes

Montanucci

Pescara

Greco

et al. 2020

Diabetes Metabolism Res

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Introduction Post‐partum umbilical cord Wharton Jelly‐derived adult mesenchymal stem cells (hUCMS) hold anti‐inflammatory and immunosuppressive properties. Human pancreatic islet‐derived progenitor cells (hIDC) may de‐differentiate, and subsequently re‐differentiate into insulin producing cells. The two cell types share common molecules that facilitate their synergistic interaction and possibly crosstalk, likely useful for the cell therapy of type 1 diabetes (T1D). Materials and methods Upon microencapsulation in sodium alginate (AG), hUCMS and hIDC were able to form cell co‐aggregates that looked well integrated and viable. We then grafted microencapsulated hUCMS/hIDC co‐aggregates into non‐obese diabetic/severe combined immunodeficient (NOD/SCID) mice, and observed an acquired ability of cells to produce and store hormones. Finally, we transplanted these biohybrid constructs into NOD mice with recent onset, spontaneous overt diabetes, observing a decline of blood glucose levels. Results In vitro, we have shown that hUCMS inhibited proliferation of allogeneic polymorphonuclear blood cells from patients with T1D, while promoting expansion of FoxP3+ Tregs. Reversal of hyperglycemia in diabetic NODs seems to suggest that hUCMS and hIDC, upon co‐microencapsulation, anatomically and functionally synergized to accomplish two goals: maintain tracer insulin output by hIDC, while exploting the immunoregulatory properties of hUCMS. Conclusion We have gathered preliminary evidence that the two adult stem cell types within AG microcapsules, may synergistically promote tracer insulin production, while “freezing” the autoimmune disease process, and help reversal of the recent onset hyperglycemia in a spontaneous, autoimmune rodent model of diabetes, the NOD mouse, with no need for pharmacologic immunosuppression.

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Plasticity and Dedifferentiation within the Pancreas: Development, Homeostasis, and Disease

Cited by 145 publications

References 120 publications

Mechanisms of Lung Fibrosis Resolution

Mechanisms of Lung Fibrosis Resolution

Endocrine Pancreas Development and Regeneration: Noncanonical Ideas From Neural Stem Cell Biology

Co‐microencapsulation of human umbilical cord‐derived mesenchymal stem and pancreatic islet‐derived insulin producing cells in experimental type 1 diabetes

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