Immunogenicity of human embryonic stem cell-derived beta cells

Area of Science:

• Stem cell biology
• Immunology
• Endocrinology

Background:

• Type 1 diabetes treatment faces donor shortages for islet transplantation.
• Human embryonic stem cells (hESCs) offer a potential unlimited source of beta cells.
• Investigating immune properties of hESC-derived cells is crucial for transplantation.

Purpose of the Study:

• To assess the immunogenicity of hESC-derived pancreatic progenitor and endocrine cells.
• To determine if immune privileged properties are maintained in differentiated hESC products.
• To inform strategies for immune intervention in hESC-based therapies.

Main Methods:

• In vivo differentiation of hESC-derived cells in mouse subcutis.
• Analysis of innate and adaptive immune responses to these cells.
• Evaluation of HLA expression and immune cell interactions.

Main Results:

• hESC-derived pancreatic endodermal cells showed low HLA, offering initial immune protection.
• IFNγ exposure upregulated HLA, increasing vulnerability to T cells and antibodies.
• In vivo-differentiated endocrine cells were targets for cellular cytotoxicity and antibody-dependent responses.

Conclusions:

• hESC-derived pancreatic progenitors are hypoimmunogenic.
• Differentiated endocrine cells are mature targets for adaptive immunity.
• Immune intervention, potentially via macro-encapsulation, is necessary for hESC-based cell transplantation.