The use of stem cells for pancreatic regeneration in diabetes mellitus

Bouwens, Luc; Houbracken, Isabelle; Mfopou, Josué Kunjom

doi:10.1038/nrendo.2013.145

Cited by 84 publications

(68 citation statements)

References 116 publications

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“…Despite the obvious appeal of a less invasive procedure, a pancreatic transplant typically has better long-term glycemic outcomes than islet transplants (Gruessner and Gruessner 2013). Sourcing sufficient human islets remains a constant challenge and stem cell technology possesses huge potential to address this need (Bouwens et al 2013). There still remain sizable issues to scaling the technology for commercial application while addressing a host of safety concerns pertaining to the potential for uncontrolled proliferation and insulin release that might evolve to be non-glucose regulated.…”

Section: Pancreatic Transplantationmentioning

confidence: 99%

Current and Emerging Treatment Options in Diabetes Care

et al. 2015

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Diabetes constitutes an increasing threat to human health, particularly in newly industrialized and densely populated countries. Type 1 and type 2 diabetes arise from different etiologies but lead to similar metabolic derangements constituted by an absolute or relative lack of insulin that results in elevated plasma glucose. In the last three decades, a set of new medicines built upon a deeper understanding of physiology and diabetic pathology have emerged to enhance the clinical management of the disease and related disorders. Recent insights into insulin-dependent and insulin-independent molecular events have accelerated the generation of a series of novel medicinal agents, which hold the promise for further advances in the management of diabetes. In this chapter, we provide a historical context for what has been accomplished to provide perspective for future research and novel emerging treatment options.

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Section: Pancreatic Transplantationmentioning

confidence: 99%

Current and Emerging Treatment Options in Diabetes Care

et al. 2015

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“…In parallel with studies using cell lines, the β-cell differentiation capacities of the pancreatic exocrine tissue was also investigated, with leaders in the field being Bouwen's and Baeyens's groups [Baeyens and Bouwens, 2008;Bouwens et al 2013] that accumulated in vitro studies both on murine and human tissues. Recent developments in their work showed the potential to induce NGN3 expression in human exocrine cells by lentiviral-induced overexpression of mitogenactivated protein kinase, and signal transducer and activator of transcription 3 [Lemper et al 2015].…”

Section: In Vitro Reprogramming Of Pancreatic Ductal Cells Into β Cellsmentioning

confidence: 99%

β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells

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et al. 2016

Therapeutic Advances in Endocrinology

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Thorough research on the capacity of human islet transplantation to cure type 1 diabetes led to the achievement of 3-to 5-year-long insulin independence in nearly half of transplanted patients. Yet, translation of this technique to clinical routine is limited by organ shortage and the need for long-term immunosuppression, restricting its use to adults with unstable disease. The production of new bona fide β cells in vitro was thus investigated and finally achieved with human pluripotent stem cells (PSCs). Besides ethical concerns about the use of human embryos, studies are now evaluating the possibility of circumventing the spontaneous tumor formation associated with transplantation of PSCs. These issues fueled the search for cell candidates for β-cell engineering with safe profiles for clinical translation. In vivo studies revealed the regeneration capacity of the exocrine pancreas after injury that depends at least partially on facultative progenitors in the ductal compartment. These stimulated subpopulations of pancreatic ductal cells (PDCs) underwent β-cell transdifferentiation through reactivation of embryonic signaling pathways. In vitro models for expansion and differentiation of purified PDCs toward insulin-producing cells were described using cocktails of growth factors, extracellular-matrix proteins and transcription factor overexpression. In this review, we will describe the latest findings in pancreatic β-cell mass regeneration due to adult ductal progenitor cells. We will further describe recent advances in human PDC transdifferentiation to insulin-producing cells with potential for clinical translational studies.

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“…So too has the reprogramming or transdifferentiation of surrogate b cells [28], although this subject is not the central theme of this review. We have recently reviewed PSCs [29], but the presence and origin of such cells has remained unverified and hotly debated.…”

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confidence: 99%