Overcoming the Challenges Now Limiting Islet Transplantation

  title={Overcoming the Challenges Now Limiting Islet Transplantation},
  author={Antonello Pileggi and Lorenzo Cobianchi and Luca A Inverardi and Camillo Ricordi},
  journal={Annals of the New York Academy of Sciences},
Abstract:  Steady improvements in islet cell processing technology and immunosuppressive protocols have made pancreatic islet transplantation a clinical reality for the treatment of patients with Type 1 diabetes mellitus (T1DM). Recent trials are showing that improved glycemic metabolic control, prevention of severe hypoglycemia, and better quality of life can be reproducibly achieved after transplantation of allogeneic islets in patients with unstable T1DM. Despite these encouraging results… 
Transplantation: current developments and future directions; the future of clinical islet transplantation as a cure for diabetes.
The steady progress and promising results of recent clinical trials justifies a great optimism toward the widespread application of beta-cell replacement as a treatment of choice for patients with diabetes.
Point: Steady Progress and Current Challenges in Clinical Islet Transplantation
The field of β-cell replacement therapies has evolved substantially over the last decades. The lesson learned from recent islet transplantation trials in patients with unstable type 1 diabetes is
Extrahepatic transplant sites for islet xenotransplantation
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Chapter 6: Patient selection for pilot clinical trials of islet xenotransplantation
The rationale for undertaking islet xenotransplantation in highly select patients with type 1diabetes and addresses some of the unique challenges is outlined.
Commentary: Insulin-Producing Organoids Engineered From Islet and Amniotic Epithelial Cells to Treat Diabetes
This publication presents the application of 3DCAgg and the use of hAECS in the construction of functional insulin-secreting organoids engineered from islet and amniotic epithelial cells to treat diabetes.
Toward Maximizing the Success Rates of Human Islet Isolation: Influence of Donor and Isolation Factors
The data suggest that a sequential, integrated approach is highly desirable to improve the success rate of islet cell processing and that improved donor management, organ recovery techniques, implementation of more stringent donor criteria, and improved islet Cell processing techniques may contribute to enhance organ utilization for transplantation.
Mesenchymal stem cells as feeder cells for pancreatic islet transplants.
New results suggest that stem/precursor cells, and mesenchymal stem cells in particular, co-transplanted with islets can promote tissue engraftment and beta-cell survival via bystander mechanisms, mainly exerted by creating a milieu of cytoprotective and immunomodulatory molecules.


Islet transplantation: steady progress and current challenges
The benefits of islet transplantation in managing patients with diabetes are tangible and very encouraging data are emerging from the numerous clinical trials and from translational research ongoing worldwide that justify cautious optimism for the near future.
Clinical islet transplantation: advances and immunological challenges
The history of and recent progress in the field, as well as the present immunological challenges and possible strategies for tolerance induction that are crucial to make clinical islet transplantation more widely available are outlined.
Update on Regulatory Issues in Pancreatic Islet Transplantation
The manufacturing challenges, discussed by the FDA advisory committee, that remain to be resolved before allogeneic islets can be approved for treatment of type 1 diabetes are highlighted.
Twenty years of clinical islet transplantation at the Diabetes Research Institute--University of Miami.
It has been a long journey and despite the intermediate success, more work is needed in order to achieve the ultimate goal of a safe and long-lasting treatment for patients with T1DM.
The Portal Immunosuppressive Storm: Relevance to Islet Transplantation?
A "portal storm" of immunosuppressant levels as well as area under the curve were dramatically elevated in portal blood relative to systemic levels for all drugs tested, suggesting that intrahepatic islet transplantation may not be optimal when these agents are absorbed via the portal vein.
Reduced fear of hypoglycemia in successful islet transplantation.
Before making this treatment available to a larger number of people with type 1 diabetes, measures of quality of care and of clinical effectiveness must be incorporated to fully evaluate the benefit of this treatment.
Islet Transplantation in Type 1 Diabetes Mellitus Using Cultured Islets and Steroid‐Free Immunosuppression: Miami Experience
  • T. Froud, C. Ricordi, R. Alejandro
  • Medicine, Biology
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2005
It is demonstrated that transplantation of cultured human islet allografts results in reproducible insulin independence in all subjects under this immunosuppressive regimen, comparable to that of freshly transplanted islets (Edmonton protocol).
Achievement of insulin independence in three consecutive type-1 diabetic patients via pancreatic islet transplantation using islets isolated at a remote islet isolation center
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Requirements for success in clinical islet transplantation.
The future success and large scale applicability of islet transplantation will rely on the synergistic research progress in critical areas that contribute to the sequential and integrated approach required for success in clinical islet transplation.
Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes.
The tested transplant protocol restored insulin independence and protected against hypoglycemia after single-donor, marginal-dose islet transplantation in 8 of 8 recipients, and may be related to improved islet engraftment secondary to peritransplant administration of antithymocyte globulin and etanercept.