Generation of stem cell-derived β-cells from patients with type 1 diabetes

Millman, Jeffrey R.; Xie, Chuncheng; Dervort, Alana Van; Gürtler, Mads; Pagliuca, Felicia W.; Melton, Douglas A.

doi:10.1038/ncomms11463

Cited by 316 publications

(312 citation statements)

References 33 publications

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“…After 72 hr of culture in mTESR1, the following steps were followed to differentiate the HUES8 clusters into SC-β cell clusters [8]. Media preparation for the differentiation protocol is as follows.…”

Section: Methodsmentioning

confidence: 99%

Economic 3D-printing approach for transplantation of human stem cell-derivedβ-like cells

Song

Millman

2016

Biofabrication

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Transplantation of human pluripotent stem cells (hPSC) differentiated into insulin-producing β cells is a regenerative medicine approach being investigated for diabetes cell replacement therapy. This report presents a multifaceted transplantation strategy that combines differentiation into stem cell-derived β (SC-β) cells with 3D printing. By modulating the parameters of a low-cost 3D printer, we created a macroporous device composed of polylactic acid (PLA) that houses SC-β cell clusters within a degradable fibrin gel. Using finite element modeling of cellular oxygen diffusion-consumption and an in vitro culture system that allows for culture of devices at physiological oxygen levels, we identified cluster sizes that avoid severe hypoxia within 3D-printed devices and developed a microwell-based technique for resizing clusters within this range. Upon transplantation into mice, SC-β cell-embedded 3D-printed devices function for 12 weeks, are retrievable, and maintain structural integrity. Here, we demonstrate a novel 3D-printing approach that advances the use of differentiated hPSC for regenerative medicine applications and serves as a platform for future transplantation strategies.

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Section: Methodsmentioning

confidence: 99%

Economic 3D-printing approach for transplantation of human stem cell-derivedβ-like cells

Song

Millman

2016

Biofabrication

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“…If allogenic iPSCs are used, these, too, will require encapsulation and/or immunomodulation, as is the case for hESCs. Alternatively, autologous iPSCs could be used, which would be given to the same individual from which they were derived, which would obviate rejection but not necessarily recurrent autoimmunity [31]. A similar approach, known as transdifferentiation, has been used in which liver cells are obtained by biopsy and differentiated in vitro into beta cells and re-implanted in the individual from whom the cells were obtained [32].…”

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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“…However, since there are protocols developed using iPSCs, it could, at least theoretically, be possible to perform autologous transplantations. In a recent publication, it was in fact shown that iPSCs from patients with T1D can be differentiated into insulin-producing cells with functional capacity equal to that of cells derived from nondiabetic individuals (66). From a patient's point of view, it would be a great benefit to receive autologous cells, since this would diminish the need for immune suppression or development of tolerance induction protocols with use of non-encapsulated transplantation.…”

Section: Autologous Vs Allogeneic Stem Cellsmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Towards the clinical translation of stem cell therapy for type 1 diabetes

Espes¹,

Lau²,

Carlsson

2017

European Journal of Endocrinology

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Insulin-producing cells derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) have for long been a promising, but elusive treatment far from clinical translation into type 1 diabetes therapy. However, the field is now on the verge of moving such insulin-producing cells into clinical trials. Although stem cell therapies provide great opportunities, there are also potential risks such as teratoma formation associated with the treatment. Many considerations are needed on how to proceed with clinical translation, including whether to use hESCs or iPSCs, and whether encapsulation of tissue will be needed. This review aims to give an overview of the current knowledge of stem cell therapy outcomes in animal models of type 1 diabetes and a proposed road map towards the clinical setting with special focus on the potential risks and hurdles which needs to be considered. From a clinical point of view, transplantation of insulin-producing cells derived from stem cells must be performed without immune suppression in order to be an attractive treatment option. Although costly and highly labour intensive, patient-derived iPSCs would be the only solution, if not clinically successful encapsulation or tolerance induction protocols are introduced.

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Generation of stem cell-derived β-cells from patients with type 1 diabetes

Cited by 316 publications

References 33 publications

Economic 3D-printing approach for transplantation of human stem cell-derivedβ-like cells

Economic 3D-printing approach for transplantation of human stem cell-derivedβ-like cells

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

MECHANISMS IN ENDOCRINOLOGY: Towards the clinical translation of stem cell therapy for type 1 diabetes

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