Cell delivery systems: Toward the next generation of cell therapies for type 1 diabetes

Dang, Hoang Phuc; Chen, Hui; Dargaville, Tim R.; Tuch, Bernard E.

doi:10.1111/jcmm.17499

Cited by 14 publications

(14 citation statements)

References 41 publications

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“…HIP p-islets not only showed prolonged survival in noninvasive monitoring over allogeneic WT p-islets but also induced no measurable immune response in the recipients. This HIP engineering strategy thus provides immune protection without the need for encapsulation strategies, which have not yet shown therapeutic efficiency ( 43 ). Alginate microencapsulated islets implanted intraperitoneally in non-immunosuppressed patients with T1DM demonstrated c-peptide secretion for 1 to 2.5 years, but the amount of insulin released was too small to alter blood glucose in a meaningful way ( 44 , 45 ).…”

Section: Discussionmentioning

confidence: 99%

Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice

Gattis

Olroyd

et al. 2023

Sci. Transl. Med.

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Transplantation of allogeneic pancreatic donor islets has successfully been performed in selected patients with difficult-to-control insulin-dependent diabetes and impaired awareness of hypoglycemia (IAH). However, the required systemic immunosuppression associated with this procedure prevents this cell replacement therapy from more widespread adoption in larger patient populations. We report the editing of primary human islet cells to the hypoimmune HLA class I– and class II–negative and CD47-overexpressing phenotype and their reaggregation into human HIP pseudoislets (p-islets). Human HIP p-islets were shown to survive, engraft, and ameliorate diabetes in immunocompetent, allogeneic, diabetic humanized mice. HIP p-islet cells were further shown to avoid autoimmune killing in autologous, diabetic humanized autoimmune mice. The survival and endocrine function of HIP p-islet cells were not impaired by contamination of unedited or partially edited cells within the p-islets. HIP p-islet cells were eliminated quickly and reliably in this model using a CD47-targeting antibody, thus providing a safety strategy in case HIP cells exert toxicity in a future clinical setting. Transplantation of human HIP p-islets for which no immunosuppression is required has the potential to lead to wider adoption of this therapy and help more diabetes patients with IAH and history of severe hypoglycemic events to achieve insulin independence.

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Section: Discussionmentioning

confidence: 99%

Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice

Gattis

Olroyd

et al. 2023

Sci. Transl. Med.

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“…Additionally, duct cells secrete angiogenic cytokines that would facilitate vascularization of the implanted site [38]. Similarly, others have demonstrated the benefits of promoting vascularization in poorly vascularized sites [39, 40], and of promoting pancreatic niche by delivering clusters in a synthetic or natural scaffold [41, 42]. Tissue remodeling may therefore be key in the establishment of a functional niche in which beta cell maturation occurs.…”

Section: Discussionmentioning

confidence: 99%

Novel MAFA+, ISL1+, NKX6-1-stem cell derived pancreatic cell clusters secrete insulin and control blood glucose in rodent models of diabetes

Ratiu,

Southard,

Rust

2023

Preprint

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This article describes a stem cell line derived by reprogramming of native human islet cells that consistently generates pure populations of endocrine pancreatic clusters following a simple differentiation protocol. Surprisingly, the population of stem cell derived pancreatic endocrine clusters that was most consistently capable of regulating blood glucose in rodent models of diabetes lacked robust expression of the key beta cell maturation-associated factor NKX6-1 but did manifest high expression of other key drivers of endocrine cell specification and maturation, ISL1 and MAFA. These data support the hypothesis that multiple pancreatic profiles can be identified in stem cell derived cultures and that these have disparate in vivo potency. The population with low NKX6-1 and high in vivo potency was further characterized by transcriptome profiling as an endocrine-committed population progressively maturing in vitro to a state proximal to the native islet.

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“…During the trial, fibrosis surrounded the PEC-Encap device and caused the stem cells to die [22]. Portions of the implant's membrane were vascularized, but not enough to be considered a success as perfusion is required for nutrient and waste exchange between the device and the body [24]. As a result, the trial was canceled prematurely and ViaCyte went back to the drawing board.…”

Section: Stem Cell Encapsulated Devicesmentioning

confidence: 99%

“…A few years later, ViaCyte partnered with W.L. Gore and Associates to test a newly modified PEC-Encap device encapsulated by a polytetrafluoroethylene membrane [24]. This design should prevent immune rejection as well as promote angiogenesis, or the formation of blood vessels.…”

Section: Stem Cell Encapsulated Devicesmentioning

confidence: 99%

“…Again, perfusion of the implant is essential for the exchange of nutrients and other materials. Patients received 12 implants in the absence of immunosuppressants to test the efficacy of insulin-producing stem cells and the polytetrafluoroethylene membrane [24]. Although the trial was expected to end in late 2022, its status remains "active" [25].…”

Section: Stem Cell Encapsulated Devicesmentioning

confidence: 99%

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Stem Cell Therapy For Type 1 Diabetes

Schweitzer,

Gallicchio

2023

JSCR

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Type 1 diabetes is an increasingly widespread autoimmune disorder that destroys the insulin-producing cells of the pancreas. Without insulin, the cells cannot insert glucose transporters into their membrane and blood sugar subsequently rises. The effects of type 1 diabetes can develop into various life-threatening conditions including heart attacks and strokes. Insulin therapy is required for type 1 diabetics, but its short-lived effects are less than ideal and often decrease quality of life. Stem cells offer a long-term solution with their ability to differentiate into insulin-producing beta cells and modulate the immune system. They can be injected directly into the body or implanted in encapsulated devices. Regardless of the technique, stem cells can restore insulin production in the body and offer a potential cure for type 1 diabetes. Stem cell therapy has a list of benefits, but the advanced technology will inevitably come with a high price tag, contributing to the increasingly inaccessible treatment options for type 1 diabetes. Should future success convince the FDA to approve its clinical use and convince insurance to cover the procedure, the long-term solution of stem cell therapy might replace insulin injections forever.

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Cell delivery systems: Toward the next generation of cell therapies for type 1 diabetes

Cited by 14 publications

References 41 publications

Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice

Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice

Novel MAFA+, ISL1+, NKX6-1-stem cell derived pancreatic cell clusters secrete insulin and control blood glucose in rodent models of diabetes

Stem Cell Therapy For Type 1 Diabetes

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