Engineering immune-evasive islet replacement: cell-intrinsic and peri-graft strategies

Area of Science:

• Biomedical Engineering
• Immunology
• Regenerative Medicine

Background:

• Type 1 diabetes treatment relies on insulin therapy, but islet transplantation offers a physiological alternative.
• Current islet transplantation faces donor scarcity, immune rejection, and limited graft survival.
• Stem cell-derived islets present a scalable option but require overcoming maturation and immune challenges.

Purpose of the Study:

• To review advancements in engineering immune-evasive islets for type 1 diabetes.
• To explore strategies for modulating the peri-graft microenvironment.
• To highlight convergent design principles for clinically deployable islet replacement therapies.

Main Methods:

• Genome editing, including CRISPR-Cas9, to engineer immune-evasive properties.
• Biomaterial and biofabrication advancements to regulate the peri-graft milieu.
• Integration of cell-intrinsic and extrinsic modulation strategies.

Main Results:

• Genome editing precisely modifies immune pathways, reducing immune recognition and inflammation.
• Biomaterials control the local microenvironment, influencing immune exposure and mass transport.
• Neither genetic modulation nor microenvironmental control alone ensures durable graft function.

Conclusions:

• Convergent design integrating immune evasion, peri-graft milieu regulation, and manufacturability is key.
• This integrated approach advances the development of clinically viable islet replacement therapies.
• Future strategies must combine multiple approaches for long-term therapeutic success.