Treating diabetes with islet transplantation: Lessons from the past decade in Lille

Vantyghem, Marie-Christine; Defrance, F.; Quintin, D.; Leroy, Clara; Raverdi, Violeta; Prévost, Gaëtan; Caïazzo, Robert; Kerr–Conte, Julie; Glowacki, François; Hazzan, Marc; Noël, Christian; Pattou, François

doi:10.1016/j.diabet.2013.10.003

Cited by 43 publications

(29 citation statements)

References 61 publications

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“…Currently, however, islet-transplantation requires chronic application of immunosuppressive therapy that restricts the use of this technique (Ryan et al, 2005; Figliuzzi et al, 2014). Up to now, only patients with unstable metabolic control, repeated severe episodes of hypoglycemia and hypoglycemic unawareness, or those with rapidly progressive diabetes-associated complications are eligible for islet-transplantation in most centers (Vantyghem et al, 2014). This will change with new technical approaches that minimize or completely prevent rejection of islets.…”

Section: Introductionmentioning

confidence: 99%

Immunological and Technical Considerations in Application of Alginate-Based Microencapsulation Systems

Juárez¹,

Spasojević²,

Faas³

et al. 2014

Front. Bioeng. Biotechnol.

150

128

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Islets encapsulated in immunoprotective microcapsules are being proposed as an alternative for insulin therapy for treatment of type 1 diabetes. Many materials for producing microcapsules have been proposed but only alginate does currently qualify as ready for clinical application. However, many different alginate-based capsule systems do exist. A pitfall in the field is that these systems are applied without a targeted strategy with varying degrees of success as a consequence. In the current review, the different properties of alginate-based systems are reviewed in view of future application in humans. The use of allogeneic and xenogeneic islet sources are discussed with acknowledging the different degrees of immune protection the encapsulation system should supply. Also issues such as oxygen supply and the role of danger associated molecular patterns (DAMPS) in immune activation are being reviewed. A common property of the encapsulation systems is that alginates for medical application should have an extreme high degree of purity and lack pathogen-associated molecular patterns (PAMPs) to avoid activation of the recipient’s immune system. Up to now, non-inflammatory alginates are only produced on a lab-scale and are not yet commercially available. This is a major pitfall on the route to human application. Also the lack of predictive pre-clinical models is a burden. The principle differences between relevant innate and adaptive immune responses in humans and other species are reviewed. Especially, the extreme differences between the immune system of non-human primates and humans are cumbersome as non-human primates may not be predictive of the immune responses in humans, as opposed to the popular belief of regulatory agencies. Current insight is that although the technology is versatile major research efforts are required for identifying the mechanical, immunological, and physico-chemical requirements that alginate-based capsules should meet for successful human application.

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Section: Introductionmentioning

confidence: 99%

Immunological and Technical Considerations in Application of Alginate-Based Microencapsulation Systems

Juárez¹,

Spasojević²,

Faas³

et al. 2014

Front. Bioeng. Biotechnol.

150

128

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“…A different approach to the treatment of T1DM is the transplantation of isolated, purified β-islet cells of the pancreas [19] to reinstitute the production of insulin in response to increases of glucose in the blood. The first clinical trial on islet transplantation in patients without kidney transplantation was performed in Pittsburgh in 1990 [20].…”

Section: Personalized Treatment Of T1dmmentioning

confidence: 99%

“…Ten years later, a successful trial was completed in Edmonton, Canada, in 2000, now seen as a landmark study [21]. The specific criteria for selecting patients for allogeneic islet transplantation are: recipients must be aged between 18 and 65 years, have T1DM for more than 5 years, have a negative fasting C-peptide (<0.3 ng/ml), exhibit hypoglycemia unawareness with glycemic lability, and have elevated HbA1c levels (above 8%) [9, 22]. The Edmonton clinical trial achieved total insulin independence in all transplanted patients for over one year, although this independence remained for 5 years in only 10% of patients [23].…”

Section: Personalized Treatment Of T1dmmentioning

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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“…Since that seminal report, technical improvements have increased the 3-year insulin-independence rate from 27% in 2002 to 44% in 2010 (2). More recently, a 5-year insulin-independence rate of 50% has been documented (3,4). However, the overall number of islet transplant recipients has remained small with just over 1000 patients worldwide (5).…”

Section: Introductionmentioning

confidence: 99%

Long-Term Immunosuppression After Solitary Islet Transplantation Is Associated With Preserved C-Peptide Secretion for More Than a Decade

Blau

Abegg

Flegel

et al. 2015

American Journal of Transplantation

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We report on two patients with type 1 diabetes (T1D) after solitary islet transplantation in 2001. They received steroid-sparing immunosuppression (daclizumab, sirolimus, and tacrolimus according to the Edmonton protocol). Both patients became insulin independent for 2 years: Patient A, a 42-year-old female with a 12-year history of T1D, received two islet infusions; patient B, a 53-year-old female with a 40-year T1D history, received one islet infusion. Pretransplant, both had undetectable C-peptide concentrations and frequent and severe hypoglycemia. Pretransplant, hemoglobin A1c (HbA1c) was 7.8% and 8.8% and insulin requirements were 0.47 and 0.33 units/kg/day, respectively. Posttransplant, C-peptide levels remained detectable while immunosuppression was continued, but decreased over time. Insulin was re-started 2 years posttransplant in both patients. Since patient A’s glycemia and insulin requirements trended toward pretransplant levels, immunosuppression was discontinued after 13 years. This resulted in a sudden cessation of C-peptide secretion. Patient B continues on immunosuppression, has better HbA1c, and half the insulin requirement compared to pretransplant. Both patients no longer experience severe hypoglycemia. Herein, we document blood glucose concentrations over time (>30 000 measurements per patient) and β cell function based on C-peptide secretion. Despite renewed insulin dependence, both patients express satisfaction with having undergone the procedure.

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Treating diabetes with islet transplantation: Lessons from the past decade in Lille

Cited by 43 publications

References 61 publications

Immunological and Technical Considerations in Application of Alginate-Based Microencapsulation Systems

Immunological and Technical Considerations in Application of Alginate-Based Microencapsulation Systems

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

Long-Term Immunosuppression After Solitary Islet Transplantation Is Associated With Preserved C-Peptide Secretion for More Than a Decade

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