Tolerance Induction and Reversal of Diabetes in Mice Transplanted with Human Embryonic Stem Cell-Derived Pancreatic Endoderm

Szot, Gregory L.; Yadav, Mahesh; Lang, Jiena; Kroon, Evert; Kerr, Justin M.; Kadoya, Kuniko; Brandon, Eugene P.; Baetge, E. Edward; Bour-Jordan, Hélène; Bluestone, Jeffrey A.

doi:10.1016/j.stem.2014.12.001

Cited by 82 publications

(67 citation statements)

References 59 publications

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“…Preclinical studies showed that when hES cell-derived PDX1 + progenitors are transplanted into mice, some of these cells undergo growth and differentiation in vivo into functional β-cells that can reverse diabetes 69,72 . These advances have led to phase I and phase II clinical trials of pancreatic progenitors.…”

Section: Strategies To Produce New Endocrine Islet Cellsmentioning

confidence: 99%

Pancreas regeneration

Zhou¹,

Melton²

2018

Nature

306

200

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The pancreas is made from two distinct components: the exocrine pancreas, a reservoir of digestive enzymes, and the endocrine islets, the source of the vital metabolic hormone insulin. Human islets possess limited regenerative ability; loss of islet β-cells in diseases such as type 1 diabetes requires therapeutic intervention. The leading strategy for restoration of β-cell mass is through the generation and transplantation of new β-cells derived from human pluripotent stem cells. Other approaches include stimulating endogenous β-cell proliferation, reprogramming non-β-cells to β-like cells, and harvesting islets from genetically engineered animals. Together these approaches form a rich pipeline of therapeutic development for pancreatic regeneration.

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Section: Strategies To Produce New Endocrine Islet Cellsmentioning

confidence: 99%

Pancreas regeneration

Zhou¹,

Melton²

2018

Nature

306

200

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“…The ability of co-stimulation blockade to protect iPSC-derived beta cells from both xenogeneic and allogeneic rejection has been reported (41). Human iPSC-derived beta cells are rapidly rejected when transplanted into immunocompetent mice.…”

Section: Pluripotent Stem Cells and Stem Cell-derived Cell Populationsmentioning

confidence: 99%

Humanized Mouse Models for Transplant Immunology

Kenney

Shultz

Greiner

et al. 2016

American Journal of Transplantation

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Our understanding of the molecular pathways that control immune responses, particularly immunomodulatory molecules that control the extent and duration of an immune response, have led to new approaches in the field of transplantation immunology to induce allograft survival. These molecular pathways are being defined precisely in murine models and translated into clinical practice; however, many of the newly available drugs are human‐specific reagents. Furthermore, many species‐specific differences exist between mouse and human immune systems. Recent advances in the development of humanized mice, namely, immunodeficient mice engrafted with functional human immune systems, have led to the availability of a small animal model for the study of human immune responses. Humanized mice represent an important preclinical model system for evaluation of new drugs and identification of the mechanisms underlying human allograft rejection without putting patients at risk. This review highlights recent advances in the development of humanized mice and their use as preclinical models for the study of human allograft responses.

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“…Coupled with such regenerative strategies, advances in genetic modification of stem cells and iPSCs may soon allow us to engineer thymus or correct defects in order to modulate and enforce tolerance. Although not ready for prime time, these therapeutic strategies have tremendous potential, considering that human embryonic stem cells have recently been used to generate both thymic epithelial progenitors (196,197) and islet-like structures (198,199) that recapitulate the function of their adult differentiated counterparts upon transplantation in mice or humanized models.…”

Section: Stability Of Tregsmentioning

confidence: 99%