Extending the “lives” of islet transplants

Extending the “lives” of islet transplants

Mari Yamamoto

Islet transplantation is a focus of many T1D researchers looking to find treatments and even a functional cure. Recently, many of these researchers have directed their studies towards overcoming hurdles like immune rejection and fibrosis that get in the way of using this strategy long-term. 

Injected therapies

Tolerogenic dendritic cells (tolDCs) have shown potential in modulating autoimmune diseases as an antigen-specific therapy. A phase 1 clinical trial tested doses of tolDCs pulsed with proinsulin peptide C19-A3, because tolDCs presenting the peptide can produce Tregs that are proinsulin-specific. The goal of the trial was to test the applicability of the therapy, which was proven to be safe without affecting overall diabetic control. 

Another approach involves the use of novel “Neo-Islets” made of pancreatic islet cells and adipose-derived stem cells. This study was an ongoing part of continued research using this technology in non-obese diabetic (NOD) mice and applying it to insulin-dependent diabetic dogs. Through intraperitoneal administration, Neo-Islets were shown to improve glycemic control without rejection, reducing insulin needs. No immune responses were observed, and the need for antirejection drugs or encapsulation devices was eliminated. This technology is very promising, as it has proven effective in long-term, larger-scale models ( dogs), without adverse immune effects. 

Encapsulation

  • A study with human-induced pluripotent stem cells (hiPSCs) showed that alginate encapsulation with single cells during hiPSC differentiation promoted proteins in an islet-like proteome direction.
    • The effects of the encapsulation were shown to be relayed through integrins, likely translating the pressure of cell confinement into signals. 
  • Researchers at MIT created an implanted device coated in a synthetic material called tetrahydropyran phenyl triazole (THPT) to encapsulate xenogeneic cells.
    • The device was tested using both human cell lines and rat islets in diabetic mice, the latter of which restored euglycemia for over 75 days. 
    • The crucial part of the design was the synthetic coating, which protected against fibrosis and was the key to the cells’ long-term survival.

Pre-vascularization

Research has proven that the subcutaneous space is effective for islet transplantation, but an obstacle remains in the way; in order to reach euglycemia, an abundance of islets is required. Pre-vascularization of the space is being explored as a way to reduce that requirement. One approach uses methacrylic acid-coated tubes to modify the space with pre-vascularization. This technique, tested in mice models and the larger rat models, showed success through a return to normal glucose levels after a marginal dose of pancreatic islets. 

Looking ahead: Though many of these approaches to improving islet transplantation are still in the testing stages, their successes in mice and even in larger animal models show hope for a longer-term treatment for T1D without the need for immunosuppression. 

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