Islet cell transplantation

Vaithilingam, Vijayaganapathy; Sundaram, Gayathri; Tuch, Bernard E.

doi:10.1097/mot.0b013e328317a48b

Cited by 31 publications

(29 citation statements)

References 32 publications

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“…Notably, thrombin is a direct mediator of inflammation, acting as a chemoattractant for neutrodiabetes mellitus, clinical outcomes remain suboptimal (63,72). In a recent report only 12% of islet recipients phils and monocytes and stimulating endothelial cells to express monocyte chemoattractant protein-1 (MCP-1) remain insulin free 1000 days after transplantation, despite implementation of the Edmonton Protocol (76).…”

Section: Introductionmentioning

confidence: 99%

Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet Transplantation

et al. 2010

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Early destruction of donor islet grafts due to an instant blood-mediated inflammatory reaction (IBMIR) remains a major obstacle in islet transplantation. Thrombomodulin plays an important role in limiting coagulation and inflammatory events through a variety of effects. In this study, we investigated the ability of thrombomodulin (TM), when reconstituted as a liposomal formulation, to enhance early syngeneic islet engraftment by minimizing or abrogating the IBMIR. Administration of TM significantly improved early engraftment of syngeneic islets after intraportal transplantation in diabetic mice. In the absence of treatment, conversion to euglycemia was observed among 46.6% (7/15) of recipients. In contrast, administration of TM led to euglycemia in 93.3% (14/15) of recipients (p = 0.0142). Recipients that received TM exhibited a lower incidence of primary nonfunction and better glucose control over a 30-day period after transplantation. Fibrin deposition (p < 0.05), neutrophil infiltration (p < 0.05), expression of TNF-α and IL-β mRNA (p < 0.05), as well as NF-κB activity (p < 0.05) were significantly reduced in the liver of islet recipients having been treated with liposomal TM. These data demonstrate that TM significantly improves early syngeneic islet engraftment through effects that target both coagulation and inflammatory pathways.

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Section: Introductionmentioning

confidence: 99%

Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet Transplantation

et al. 2010

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“…16 The engraftment and function of transplanted islets can be impaired by the isolation process that severs critical vascular connections and disrupts interactions between islet cells and their ECM. [18][19][20][21][22][23][24][25][26][27] These interactions regulate many aspects of islet physiology, including survival, proliferation, and insulin secretion. 15,23,28 Reconstruction of islet cell-ECM relationships following isolation mitigates the loss of differentiated islet structure and function, reduces apoptosis and necrosis of b-cells, 29 and increases insulin secretion.…”

mentioning

confidence: 99%

Collagen IV-Modified Scaffolds Improve Islet Survival and Function and Reduce Time to Euglycemia

Yap

Salvay

Silliman

et al. 2013

Tissue Engineering Part A

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Islet transplantation on extracellular matrix (ECM) protein-modified biodegradable microporous poly(lactide-coglycolide) scaffolds is a potential curative treatment for type 1 diabetes mellitus (T1DM). Collagen IV-modified scaffolds, relative to control scaffolds, significantly decreased the time required to restore euglycemia from 17 to 3 days. We investigated the processes by which collagen IV-modified scaffolds enhanced islet function and mediated early restoration of euglycemia post-transplantation. We characterized the effect of collagen IVmodified scaffolds on islet survival, metabolism, and insulin secretion in vitro and early-and intermediate-term islet mass and vascular density post-transplantation and correlated these with early restoration of euglycemia in a syngeneic mouse model. Control scaffolds maintained native islet morphologies and architectures as well as collagen IV-modified scaffolds in vivo. The islet size and vascular density increased, while b-cell proliferation decreased from day 16 to 113 post-transplantation. Collagen IV-modified scaffolds promoted islet cell viability and decreased early-stage apoptosis in islet cells in vitro-phenomena that coincided with enhanced islet metabolic function and glucose-stimulated insulin secretion. These findings suggest that collagen IV-modified scaffolds promote the early restoration of euglycemia post-transplantation by enhancing islet metabolism and glucose-stimulated insulin secretion. These studies of ECM proteins, in particular collagen IV, and islet function provide key insights for the engineering of a microenvironment that would serve as a platform for enhancing islet transplantation as a viable clinical therapy for T1DM.

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“…Transplantation of encapsulated islets to reverse hyperglycemia in diabetic animals has been reported by many researchers (Mikos et al 1994, Efrat 2002, Orive et al 2003, Kizilel et al 2005, Zimmermann et al 2005, Vaithilingam et al 2008, Abalovich et al 2009). However, this approach has been severely limited by the lack of islet donors.…”

Section: Discussionmentioning

confidence: 99%

“…Like transplantation of encapsulated islets (van Schilfgaarde & de Vos 1999, Vaithilingam et al 2008, Abalovich et al 2009), the relapse of hyperglycemia observed 2 . 5 months after transplantation of encapsulated MEPI-1 cells in diabetic mice might involve three major scenarios.…”

Section: Discussionmentioning

confidence: 99%

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Correction of Hyperglycemia in Type 1 Diabetic Models by Transplantation of Encapsulated Insulin-producing Cells Derived from Mouse Embryo Progenitor

Shao¹,

Gao²,

Xie³

et al. 2011

Journal of Endocrinology

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Shortage of cadaveric pancreata and requirement of immune suppression are two major obstacles in transplantation therapy of type 1 diabetes. Here, we investigate whether i.p. transplantation of alginate-encapsulated insulin-producing cells from the embryo-derived mouse embryo progenitorderived insulin-producing-1 (MEPI-1) line could lower hyperglycemia in immune-competent, allogeneic diabetic mice. Within days after transplantation, hyperglycemia was reversed followed by about 2 . 5 months of normo-to moderate hypoglycemia before relapsing. Mice transplanted with unencapsulated MEPI cells relapsed within 2 weeks. Removal of the transplanted capsules by washing of the peritoneal cavity caused an immediate relapse of hyperglycemia that could be reversed with a second transplantation. The removed capsules had fibrotic overgrowth but remained permeable to 70 kDa dextrans and displayed glucose-stimulated insulin secretion.Following transplantation, the number of cells in capsules increased initially, before decreasing to below the starting cell number at 75 days. Histological examination showed that beyond day 40 post-transplantation, encapsulated cell clusters exhibited proliferating cells with a necrotic core. Blood glucose, insulin levels, and oral glucose tolerance test in the transplanted animals correlated directly with the number of viable cells remaining in the capsules. Our study demonstrated that encapsulation could effectively protect MEPI cells from the host immune system without compromising their ability to correct hyperglycemia in immune-competent diabetic mice for 2 . 5 months, thereby providing proof that immunoisolation of expansible but immune-incompatible stem cell-derived surrogate b-cells by encapsulation is a viable diabetes therapy.

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Islet cell transplantation

Abstract: The above strategies are likely to enhance the outcomes of clinical islet transplants.

Cited by 31 publications

References 32 publications

Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet Transplantation

Liposomal Formulations of Thrombomodulin Increase Engraftment after Intraportal Islet Transplantation

Collagen IV-Modified Scaffolds Improve Islet Survival and Function and Reduce Time to Euglycemia

Correction of Hyperglycemia in Type 1 Diabetic Models by Transplantation of Encapsulated Insulin-producing Cells Derived from Mouse Embryo Progenitor

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