Prolonged Survival of Microencapsulated Neonatal Porcine Islet Xenografts in Immune-Competent Mice without Antirejection Therapy

Kobayashi, T; Arefanian, Hossein; Harb, George; Tredget, Eric B.; Rajotte, Ray V.; Korbutt, Gregory S.; Rayat, Gina R.

doi:10.3727/096368908787236602

Cited by 20 publications

(16 citation statements)

References 22 publications

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“…In addition, maturation of neonatal islets is one of the important factors for proper insulin secretory ability (Kobayashi et al, 2008). In this study, we did not assess the maturity of neonatal islets before transplantation, however; we plan to assess the maturity of neonatal islets before transplantation for the next clinical trial.…”

Section: Discussionmentioning

confidence: 99%

Clinical Benefit of Islet Xenotransplantation for the Treatment of Type 1 Diabetes

Matsumoto¹,

Abalovich²,

Wechsler³

et al. 2016

EBioMedicine

177

170

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BackgroundAllogeneic islet transplantation has become a viable option for the treatment of unstable type 1 diabetes. However, the donor shortage and the necessity of the immunosuppressive drugs are two major issues. To solve these issues, we performed islet xenotransplantation using encapsulated neonatal porcine islets without immunosuppressive drugs.MethodsTwo different doses (approximately 5000 IEQ/kg and 10,000 IEQ/kg) of encapsulated neonatal porcine islets were transplanted twice (total approximately 10,000 IEQ/kg and 20,000 IEQ/kg) into four type 1 diabetic patients in each group (total 8 patients).FindingsIn the higher dose group, all four patients improved HbA1c. This was maintained at a level of < 7% for > 600 days with significant reduction of the frequency of unaware hypoglycemic events.InterpretationThe clinical benefit of islet xenotransplantation with microencapsulation has been shown.

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Section: Discussionmentioning

confidence: 99%

Clinical Benefit of Islet Xenotransplantation for the Treatment of Type 1 Diabetes

Matsumoto¹,

Abalovich²,

Wechsler³

et al. 2016

EBioMedicine

177

170

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“…The proposed mechanism is by providing an extracellular support matrix to the NPI, and a possible barrier to the action of CD4 + T cells. While some groups have reported that microencapsulated porcine islets can survive after xenotransplantation without the use of immunosuppressive medications (Duvivier-Kali et al, 2004;Sun et al, 1996), there is further evidence that microencapsulation alone is likely not sufficient to prevent rejection (Kobayashi et al, 2005(Kobayashi et al, , 2008. When microencapsulated NPI are transplanted into immune competent mice without the use of immunosuppressive medications, a progressive amount of CD4 + T cells, macrophages, and B cells are seen on the surface of the capsule over time.…”

Section: Microencapsulation Of Npimentioning

confidence: 99%

“…The in vivo maturation of microencapsulated NPI in immunodeficient mice did improve the survival of the grafts in subsequent transplantation into immune competent mice. This seems to be due to the maturation of intact NPI and a decrease in their immunogenicity (Kobayashi et al, 2008). Microencapsulated islet graft survival can be prolonged when the combination of anti-LFA-1 and anti-CD154 mAbs are also administered in vivo.…”

Section: Microencapsulation Of Npimentioning

confidence: 99%

Porcine Islet Xenotransplantation for the Treatment of Type 1 Diabetes

Mihalicz¹,

Rajotte²,

Rayat³

2011

Type 1 Diabetes - Pathogenesis, Genetics and Immunotherapy

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“…Many open questions regarding experimental diabetes treatment modalities have been answered in studies using small animal diabetes models. Such studies, for example, have answered fundamental questions regarding the appropriate transplantation site for islets cells [13,14], the function of islets cell transplants in vivo [15,16], the recipient immune response to islets cell transplants [17], and regarding postoperative glucose homeostasis in the field of diabetes metabolism research [18]. As valuable as such studies are, however, questions regarding the feasibility of such concepts under preclinical conditions can only be answered in large animal models of diabetes.…”

Section: Introductionmentioning

confidence: 99%

Goettingen Minipigs (GMP): Comparison of Two Different Models for Inducing Diabetes

Strauss

Moskalenko

Tiurbe

et al. 2012

Diabetol Metab Syndr

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PurposePreclinical experiments on large animals are indispensable for evaluating the effectiveness of diabetes therapies. Miniature swine are well suited for such studies due to their physiological and pathophysiological responses.MethodsWe compare two methods for inducing diabetes in Goettingen minipigs (GMP), in five with the beta cell toxin streptozotocin (STZ) and in five other GMP by total pancreatectomy (PE). Glucose homeostasis was assessed with the intravenous glucose-tolerance test (IVGTT) and continual monitoring of interstitial glucose levels. At conclusion of the observation period, the pancreata were examined histologically. Three non-diabetic GMP served as control group.ResultsThe IVGTT revealed markedly diabetic profiles in both GMP groups. STZ-GMP were found to harbor residual C-peptides and scattered insulin-positive cells in the pancreas. PE-GMP survived the total pancreatectomy only with intensive postoperative care.ConclusionsAlthough both methods reliably induced diabetes in GMP, the PE-GMP clearly had more health problems and required a greater expenditure of time and resources. The PE-GMP model, however, was better at eliminating endogenous insulin and C-peptide than the STZ-GMP model.

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Prolonged Survival of Microencapsulated Neonatal Porcine Islet Xenografts in Immune-Competent Mice without Antirejection Therapy

Cited by 20 publications

References 22 publications

Clinical Benefit of Islet Xenotransplantation for the Treatment of Type 1 Diabetes

Clinical Benefit of Islet Xenotransplantation for the Treatment of Type 1 Diabetes

Porcine Islet Xenotransplantation for the Treatment of Type 1 Diabetes

Goettingen Minipigs (GMP): Comparison of Two Different Models for Inducing Diabetes

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