Pancreatic islet transplantation

Johnson, Paul; Jones, Katherine E.

doi:10.1053/j.sempedsurg.2012.05.012

Cited by 38 publications

(22 citation statements)

References 35 publications

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“…Only the endocrine component of the pancreas is transplanted in this case (~2-3% of the pancreas mass), considerably reducing the risks of the surgical procedure(17). Islets are usually injected in the portal vein and transported via the bloodstream into the liver where they take up residence(16).…”

Section: Introductionmentioning

confidence: 99%

“…Islets are usually injected in the portal vein and transported via the bloodstream into the liver where they take up residence(16). Over 1400 islet transplantation procedures have been performed worldwide since 1974(17). These transplantations lacked success before 2000: only 8% of recipients maintained insulin independence one year after transplantation from 1990 to 1998(19).…”

Section: Introductionmentioning

confidence: 99%

“…A normal human pancreas contains roughly 1 million islets(11); however islets purified from donor pancreases require several steps to be ready for transplantation, and all these steps can be detrimental to the harvested islets(17). Consequently, 2-4 donor pancreases are required to perform a successful islet transplantation procedure(17).…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, 2-4 donor pancreases are required to perform a successful islet transplantation procedure(17). The significant mismatch between the number of islets needed for transplantation and the islet availability highlights the urgent need to find additional islet sources.…”

Section: Introductionmentioning

confidence: 99%

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Membranes to achieve immunoprotection of transplanted islets

2014

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Transplantation of islet or beta cells is seen as the cure for type 1 diabetes since it allows physiological regulation of blood glucose levels without requiring any compliance from the patients. In order to circumvent the use of immunosuppressive drugs (and their side effects), semipermeable membranes have been developed to encapsulate and immunoprotect transplanted cells. This review presents the historical developments of immunoisolation and provides an update on the current research in this field. A particular emphasis is laid on the fabrication, characterization and performance of membranes developed for immunoisolation applications.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Membranes to achieve immunoprotection of transplanted islets

2014

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“…These drawbacks include the need for longterm immunosuppression therapy, as well as the heightened risk of mortality and morbidity associated with major transplant surgery. [19] Due to these risks, pancreas transplantation is often limited to a select group of individuals who have either already undergone successful kidney transplantation or are receiving simultaneous kidney-pancreas transplants and therefore already require immunosuppressant drugs.…”

Section: Transplantation Of Pancreatic Islets Of Langerhansmentioning

confidence: 99%

Microfluidic Device Design for Selective Enrichment of Biocolloids Based on their Deformability and Polarization

Varhue

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The development of methods to achieve the selective enrichment and separation of biocolloids based on particle size, shape, biomechanical properties, cell phenotype, and biomolecular conformation is of great interest towards application in tissue regeneration and bioanalytical systems. Microfluidic systems enable the selective translation of particles by hydrodynamic means based on size, shape and deformability. Furthermore, separation can be achieved through the integration of electrokinetic methods such as dielectrophoresis (DEP), which enables frequency selective translation of bioparticles based on dielectric parameters, including intracellular electrophysiology, surface topology, and bimolecular conformation. Herein we develop microfluidic device platforms for two clinically significant applications: (1) deformability-based separation of pancreatic islets of Langerhans from exocrine acinar tissue; and (2) simultaneous enrichment and detection of proteomic biomarkers in physiological media.Diabetes remains the seventh leading cause of death among Americans. A potential cure for the type-1 variant, which is currently managed through lifelong exogenous insulin administration, can be achieved through transplantation of pancreatic islet of Langerhans to restore normal endocrinal function. However, endocrine islet tissue forms a small proportion of the pancreas (~1%), and must be isolated from the contaminating exocrine acinar tissue that makes up the majority of the organ. Herein, we demonstrate that the density gradient based method that is currently used to separate islets from acinar tissue causes the islets to be sparsely distributed across a wide array of centrifuged sample bins of varying purity. The resulting transplant plug contains significantly high levels of contaminating exocrine acinar tissue (~40% of transplant volume), thereby exacerbating immune responses and requiring the life-long administration of immune suppressants after transplantation. In comparison to the significant size and density overlaps between the islet and acinar tissue populations, we demonstrate that their deformability overlaps are minimal. Utilizing this feature, we demonstrate a microfluidic separation strategy, wherein tangential flows enable selective deformation of acinar populations towards the waste stream and sequential switching of hydrodynamic resistance enables the collection of rigid islet cell aggregates. This system is shown to be capable of enriching islets from relatively dilute starting levels up to purity levels that meet transplant criteria, as well as towards enhancing islet purity from the starting samples obtained after density gradient based separation.The electrokinetic trapping of nanoscale biocolloids and biomolecules within nanoslit devices enables high degrees of enrichment and overcomes mass transport limitations within various sensing modalities. Such nanoslit device architectures are applied to enable the simultaneous trapping and detection of two important proteomic biomarkers: (i) Neurop...

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Fibrin gels engineered with pro‐angiogenic growth factors promote engraftment of pancreatic islets in extrahepatic sites in mice

Najjar

Manzoli

Abreu

et al. 2015

Biotech & Bioengineering

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With a view toward reduction of graft loss, we explored pancreatic islet transplantation within fibrin matrices rendered pro-angiogenic by incorporation of minimal doses of vascular endothelial growth factor-A165 and platelet-derived growth factor-BB presented complexed to a fibrin-bound integrin-binding fibronectin domain. Engineered matrices allowed for extended release of pro-angiogenic factors and for their synergistic signaling with extracellular matrix-binding domains in the post-transplant period. Aprotinin addition delayed matrix degradation and prolonged pro-angiogenic factor availability within the graft. Both subcutaneous (SC) and epididymal fat pad (EFP) sites were evaluated. We show that in the SC site, diabetes reversal in mice transplanted with 1,000 IEQ of syngeneic islets was not observed for islets transplanted alone, while engineered matrices resulted in a diabetes median reversal time (MDRT) of 38 days. In the EFP site, the MDRT with 250 IEQ of syngeneic islets within the engineered matrices was 24 days versus 86 days for islets transplanted alone. Improved function of engineered grafts was associated with enhanced and earlier (by day 7) angiogenesis. Our findings show that by engineering the transplant site to promote prompt re-vascularization, engraftment and long-term function of islet grafts can be improved in relevant extrahepatic sites.

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Pancreatic islet transplantation

Cited by 38 publications

References 35 publications

Membranes to achieve immunoprotection of transplanted islets

Membranes to achieve immunoprotection of transplanted islets

Microfluidic Device Design for Selective Enrichment of Biocolloids Based on their Deformability and Polarization

Fibrin gels engineered with pro‐angiogenic growth factors promote engraftment of pancreatic islets in extrahepatic sites in mice

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