Pancreas Transplantation: Solid Organ and Islet

Mittal, Shruti; Johnson, Paul; Friend, Peter J.

doi:10.1101/cshperspect.a015610

Cited by 30 publications

(21 citation statements)

References 74 publications

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“…Unfortunately, given the low-volume nature of pancreas transplantation, the evidence for advantages or disadvantages of specific immunosuppressive regimens is quite limited. Currently, most centers use induction therapy with antithymocyte globulin, alemtuzumab, or basiliximab [ 12 , 13 ]. Most SPK patients receive a depleting antibody agent, such as alemtuzumab or antithymocyte globulin [ 6 , 14 ] (Fig.…”

Section: Advances In Immunosuppressionmentioning

confidence: 99%

Simultaneous pancreas and kidney transplantation

Redfield¹,

Scalea²,

Odorico³

2015

Current Opinion in Organ Transplantation

104

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Purpose of reviewImportant trends are being observed in pancreas transplantation in the USA. We will describe recent trends in simultaneous pancreas kidney (SPK) transplantation related to immunosuppression, treatment of rejection, and transplantation for patients of advanced age and C-peptide positive diabetes.Recent findingsRates of pancreas transplantation have declined, despite improved pancreatic graft outcomes. Regarding immunosuppression, trends in SPK transplantation include T-cell depletion induction therapy, waning mammalian target of rapamycin inhibitor use and steroid use in greater than 50% of pancreas transplant recipients with few patients undergoing late steroid weaning. Rejection of the pancreas may be discordant with the kidney after SPK and there is a greater appreciation of antibody-mediated rejection of the pancreas allograft. De-novo donor-specific antibody without graft dysfunction remains an active area of study, and the treatment for this condition is unclear. SPKs are being performed with greater frequency in type 2 diabetes mellitus patients and in patients of advanced age, with exemplary results.SummaryThe current state of the art in SPK transplantation is yielding superb and improving results.

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Section: Advances In Immunosuppressionmentioning

confidence: 99%

Simultaneous pancreas and kidney transplantation

Redfield¹,

Scalea²,

Odorico³

2015

Current Opinion in Organ Transplantation

104

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“…We suggest that these pancreata be utilised to study the composition of the human pancreatic ECM, and potentially be used for bioengineering and regenerative medicine purposes. Donor selection is very stringent for pancreas transplant, and as a result many are declined based on medical history, fibrosis, fat deposition and other conservative practises 33 even though the pancreas is healthy and functional. These pancreata could be decellularized, processed to construct biomaterials, such as hydrogels, and used for tissue engineering applications rather than be discarded.…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix scaffold and hydrogel derived from decellularized and delipidized human pancreas

Sackett

Tremmel

et al. 2018

Sci Rep

224

164

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Extracellular matrix (ECM) plays an important developmental role by regulating cell behaviour through structural and biochemical stimulation. Tissue-specific ECM, attained through decellularization, has been proposed in several strategies for tissue and organ replacement. Decellularization of animal pancreata has been reported, but the same methods applied to human pancreas are less effective due to higher lipid content. Moreover, ECM-derived hydrogels can be obtained from many decellularized tissues, but methods have not been reported to obtain human pancreas-derived hydrogel. Using novel decellularization methods with human pancreas we produced an acellular, 3D biological scaffold (hP-ECM) and hydrogel (hP-HG) amenable to tissue culture, transplantation and proteomic applications. The inclusion of a homogenization step in the decellularization protocol significantly improved lipid removal and gelation capability of the resulting ECM, which was capable of gelation at 37 °C in vitro and in vivo, and is cytocompatible with a variety of cell types and islet-like tissues in vitro. Overall, this study demonstrates the characterisation of a novel protocol for the decellularization and delipidization of human pancreatic tissue for the production of acellular ECM and ECM hydrogel suitable for cell culture and transplantation applications. We also report a list of 120 proteins present within the human pancreatic matrisome.

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“…However, other options now exist that can provide a finely regulated and on-demand insulin production from within, such as transplantation of the whole pancreas [6, 8], transplantation of isolated, naked pancreatic islets [9, 10], and transplantation of immuno-isolated or microencapsulated pancreatic islets [11, 12]. …”

Section: Personalized Treatment Of T1dmmentioning

confidence: 99%

“…Ideally, all patients that are inadequately regulated by insulin injections should be transplanted with a tightly regulating insulin-producing graft. However, in those patients the side effects of immunosuppression do not outweigh the risk of complications of insulin therapy and for that reason it is now only performed in those patients where end-stage renal failure occurred [6]. A combination of a kidney and an islet cell graft is usually given.…”

Section: Introductionmentioning

confidence: 99%

Recent progress in the use and tracking of transplanted islets as a personalized treatment for type 1 diabetes

Paredes-Juarez

Vos

Bulte

2017

Expert Review of Precision Medicine and Drug Development

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Introduction Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the pancreas produces insufficient amounts of insulin. T1DM patients require exogenous sources of insulin to maintain euglycemia. Transplantation of naked or microencapsulated pancreatic islets represents an alternative paradigm to obtain an autonomous regulation of blood glucose levels in a controlled and personalized fashion. However, once transplanted, the fate of these personalized cellular therapeutics is largely unknown, justifying the development of non-invasive tracking techniques. Areas covered In vivo imaging of naked pancreatic islet transplantation, monitoring of microencapsulated islet transplantation, visualizing pancreatic inflammation, imaging of molecular-genetic therapeutics, imaging of beta cell function. Expert commentary There are still several hurdles to overcome before (microencapsulated) islet cell transplantation will become a mainstay therapy. Non-invasive imaging methods that can track graft volume, graft rejection, graft function (insulin secretion) microcapsule engraftment, microcapsule rupture, and pancreatic inflammation are currently being developed to design the best experimental transplantation paradigms.

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Pancreas Transplantation: Solid Organ and Islet

Cited by 30 publications

References 74 publications

Simultaneous pancreas and kidney transplantation

Simultaneous pancreas and kidney transplantation

Extracellular matrix scaffold and hydrogel derived from decellularized and delipidized human pancreas

Recent progress in the use and tracking of transplanted islets as a personalized treatment for type 1 diabetes

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