Cell Replacement Therapy: The Rationale for Encapsulated Porcine Islet Transplantation

Skinner, S.J.M.; Tan, Paul; Garkavenko, Olga; Muzina, Marija; Escobar, Livia; Elliott, Robert B.

doi:10.5772/24824

Cited by 3 publications

(9 citation statements)

References 45 publications

(44 reference statements)

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“…The initial pilots showed no signs of inflammation or fibrosis, and no porcine endogenous retroviral infection, with a reduction in daily insulin dose and HbA 1c levels in the transplanted patients. Furthermore, microcapsules that were retrieved 9.5 years after transplantation contained viable cells that produced insulin in response to glucose stimulation (5,24,40). In 2009 the company initiated a Phase I/IIa dose-finding study (NCT00940173) with 14 patients, for which they reported improved hypoglycemic awareness and elimination of hypoglycemic convulsions in one patient in 2011 (5).…”

Section: Xenotransplantationmentioning

confidence: 98%

“…To prevent rejection of xenografts, encapsulation devices have been used to protect against the immune response generated by porcine cell surface antigens. Encapsulation can also provide protection from xenosis, which has been a concern in the use of animal cells in humans (5,7,24,34).…”

Section: Xenotransplantationmentioning

confidence: 99%

“…Encapsulation aims to create an artificial immune-privileged site, protecting the grafts from the host immune system. A successful device should contain membranes with selective permeability, to exclude large host immune cells and immunoglobulins, while permitting small molecules such as oxygen, carbon dioxide and essential nutrients to reach the cells, and insulin to be secreted in response to high blood glucose levels (5,24,25). Graft site is also an important consideration when designing an encapsulation device, as engrafted islets/cells must be able to respond rapidly to elevated circulating glucose levels.…”

Section: Whole Pancreas and Islet Transplantationmentioning

confidence: 99%

“…However, current trials, run by Living Cell Technologies, are testing the safety and efficacy of encapsulated pig islets transplanted into human T1DM patients without immunosuppression (5,24,40,41). The islets are sourced from a pathogen-free, isolated herd of Auckland Islands pigs and encapsulated in alginate microcapsules (42,43).…”

Section: Xenotransplantationmentioning

confidence: 99%

“…Although insulin treatment has substantially improved life expectancy, there is still substantial morbidity and mortality associated with the disease (5). While helping to control blood glucose levels, administration of exogenous insulin does not provide as precise regulation as functional islets, resulting in fluctuations between hypo-and hyper-glycemic states.…”

mentioning

confidence: 99%

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Recent Advances in Cell Replacement Therapies for the Treatment of Type 1 Diabetes

Cogger

Nostro

2015

Endocrinology

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Exogenous insulin administration is currently the only treatment available to all type 1 diabetes patients, but it is not a cure. By helping to regulate circulating blood glucose levels, it has significantly improved life expectancy, but there are still long-term complications associated with the disease that may be preventable with a treatment strategy that can provide better glycemic control. Isolated islet (or whole pancreas) transplantation, xenotransplantation, and the transplant of human pluripotent stem cell-derived β-cells provide the potential to restore endogenous insulin production and reestablish normoglycemia. Here, we discuss the latest advances in these fields, including the use of encapsulation technology, as well as some of the hurdles that still need to be overcome for these alternative therapies to become mainstream and/or progress to clinical development.

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Section: Xenotransplantationmentioning

confidence: 98%

Section: Xenotransplantationmentioning

confidence: 99%

Section: Whole Pancreas and Islet Transplantationmentioning

confidence: 99%

Section: Xenotransplantationmentioning

confidence: 99%

mentioning

confidence: 99%

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Recent Advances in Cell Replacement Therapies for the Treatment of Type 1 Diabetes

Cogger

Nostro

2015

Endocrinology

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Stem Cells in the Treatment of InsulinDependent Diabetes Mellitus

et al. 2016

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Diabetes affects over 350 million people worldwide, with the figure projected to rise to nearly 500 million over the next 20 years, according to the World Health Organization. Insulin-dependent diabetes mellitus (type 1 diabetes) is an endocrine disorder caused by an autoimmune reaction that destroys insulin-producing -cells in the pancreas, which leads to insulin deficiency. Administration of exogenous insulin remains at the moment the treatment mainstay. This approach helps to regulate blood glucose levels and significantly increases the life expectancy of patients. However, type 1 diabetes is accompanied by long-term complications associated with the systemic nature of the disease and metabolic abnormalities having a profound impact on health. Of greater impact would be a therapeutic approach which would overcome these limitations by better control of blood glucose levels and prevention of acute and chronic complications. The current efforts in the field of regenerative medicine are aimed at finding such an approach. In this review, we discuss the time-honored technique of donor islets of Langerhans transplantation. We also focus on the use of pluripotent stem and committed cells and cellular reprogramming. The molecular mechanisms of pancreatic differentiation are highlighted. Much attention is devoted to the methods of grafts delivery and to the materials used during its creation.

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Clinical Islet Xenotransplantation: Development of Isolation Protocol, Anti-Rejection Strategies, and Clinical Outcomes

Matsumoto,

Matsumoto

2024

Cells

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Allogeneic islet transplantation has become a standard therapy for unstable type 1 diabetes. However, considering the large number of type 1 diabetic patients, the shortage of donors is a serious issue. To address this issue, clinical islet xenotransplantation is conducted. The first clinical islet xenotransplantation was performed by a Swedish team using fetal pancreatic tissue. Thereafter, clinical trials of islet xenotransplantation were conducted in New Zealand, Russia, Mexico, Argentina, and China using neonatal pig islets. In clinical trials, fetal or neonatal pancreata are used because of the established reliable islet isolation methods. These trials demonstrate the method’s safety and efficacy. Currently, the limited number of source animal facilities is a problem in terms of promoting islet xenotransplantation. This limitation is due to the high cost of source animal facilities and the uncertain future of xenotransplantation. In the United States, the first xenogeneic heart transplantation has been performed, which could promote xenotransplantation. In Japan, to enhance xenotransplantation, the ‘Medical Porcine Development Association’ has been established. We hope that xenogeneic transplantation will become a clinical reality, serving to address the shortage of donors.

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Cell Replacement Therapy: The Rationale for Encapsulated Porcine Islet Transplantation

Cited by 3 publications

References 45 publications

Recent Advances in Cell Replacement Therapies for the Treatment of Type 1 Diabetes

Recent Advances in Cell Replacement Therapies for the Treatment of Type 1 Diabetes

Stem Cells in the Treatment of InsulinDependent Diabetes Mellitus

Clinical Islet Xenotransplantation: Development of Isolation Protocol, Anti-Rejection Strategies, and Clinical Outcomes

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