Islet Cell Transplantion: Update on Current Clinical Trials

Schuetz, Christian; Markmann, James F.

doi:10.1007/s40472-016-0103-z

Cited by 26 publications

(22 citation statements)

References 121 publications

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“…Analysis from the Collaborative Islet Transplant Registry shows that factors that predict recipient insulin independence include recipient age >35 years, islet equivalents infused >500,000, islet stimulation index >1.5, and induction therapy with T-cell depletion and TNFα inhibitor followed by maintenance therapy with mTOR and calcineurin inhibitors. 4 Despite lower rates of long-term insulin independence, there are other very important benefits from islet transplantation. In a study by Hering et al, 87.5% of the patients at 1 year met primary end points of HbA1c <7.0% (on or off insulin therapy) and freedom from SHEs; 71% of the patients met these end points at 2 years.…”

Section: Clinical Outcomesmentioning

confidence: 99%

“…Furthermore, to reduce the high donor to recipient requirements for islet cell transplantation and to make the therapy more broadly available, research is being conducted to find alternative sources of pancreatic β islet cells, including from allogeneic human embryonic stem cells or xenogeneic porcine islets cells. 4…”

Section: Future Directionsmentioning

confidence: 99%

“…In fact, severe hypoglycemic events account for 4 to 14.5% of T1DMrelated mortality. 4 The purpose of pancreas transplantation is to re-establish physiologic normoglycemia. 5 Transplantation provides tight glycemic control to reduce episodes of hypoglycemia.…”

mentioning

confidence: 99%

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Role of the Interventional Radiologist in Pancreatic Whole Organ and Islet Cell Transplantation

et al. 2019

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Pancreas transplantation is an exciting therapy which has been used for several decades in the treatment of diabetes mellitus. It can be performed as either a whole organ or islet cell transplant. The role of interventional radiologists in the management of whole organ transplants is evolving and includes treatment of postoperative complications and graft biopsy to evaluate for rejection. An in-depth understanding of the transplant anatomy and variations is a fundamental tool in performing these interventions successfully. Islet cell transplantation entails delivery of purified donor pancreatic islet cells into the recipient portal vein. Because of their expertise in image-guided access to the portal system, interventional radiologists play a crucial role in this procedure. The purpose of this article is to review the indications, anatomy, complications, and outcomes of both whole organ and islet cell pancreas transplants, followed by a discussion of the role of interventional radiologists in each procedure.

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Section: Clinical Outcomesmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

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Role of the Interventional Radiologist in Pancreatic Whole Organ and Islet Cell Transplantation

et al. 2019

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“…In the most severe cases, asymptomatic hypoglycemia can result in coma or death. Transplantation of insulin-secreting cells is indicated in individuals with labile T1D to replenish the insulin source and restore glucose homeostasis (Dean et al, 2017;Schuetz and Markmann, 2016;Shapiro et al, 2017). The islet transplantation field has grown tremendously in the past decades .…”

Section: Introductionmentioning

confidence: 99%

Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes

et al. 2020

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The scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Transplantation of encapsulated stem cell-derived islets (SC islets) might extend the applicability of islet transplantation to a larger cohort of patients. Transplantation of conformal-coated islets into a confined well-vascularized site allows long-term diabetes reversal in fully MHC-mismatched diabetic mice without immunosuppression. Here, we demonstrated that human SC islets reaggregated from cryopreserved cells display glucose-stimulated insulin secretion in vitro. Importantly, we showed that conformally coated SC islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. Overall, these results provide support for further evaluation of safety and efficacy of conformal-coated SC islets in larger species.

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“…Total pancreatectomy and islet autotransplantation (TP-IAT) is a safe and effective approach in the management of intractable pain associated with chronic pancreatitis (CP) 1 . Although quality-of-life parameters are measurably improved in IAT patients, the insulin independence rate after TP-IAT is still low [2][3][4] . Major hurdles besetting this procedure in CP individuals include the limited number of functional islets available for transplantation from a severely diseased and fibrotic pancreas, and islet cell death caused by stresses encountered after pancreatectomy, during islet isolation, and post-transplantation.…”

Section: Introductionmentioning

confidence: 99%

Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation

et al. 2019

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Stresses encountered during human islet isolation lead to unavoidable b-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, b-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less b-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.

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Islet Cell Transplantion: Update on Current Clinical Trials

Cited by 26 publications

References 121 publications

Role of the Interventional Radiologist in Pancreatic Whole Organ and Islet Cell Transplantation

Role of the Interventional Radiologist in Pancreatic Whole Organ and Islet Cell Transplantation

Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes

Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation

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