Generating hESCs with reduced immunogenicity by disrupting TAP1 or TAPBP

Area of Science:

• Stem Cell Biology
• Immunology
• Gene Editing

Background:

• Human embryonic stem cells (hESCs) hold promise for cell therapy but face immunological rejection.
• Major histocompatibility complex (MHC) class I expression on cell surfaces is a primary driver of graft rejection.
• Transporter associated with antigen presentation 1 (TAP1) and TAP-associated glycoprotein (TAPBP) are key regulators of MHC class I expression.

Purpose of the Study:

• To generate human embryonic stem cell (hESC) lines deficient in TAP1 and TAPBP.
• To evaluate the impact of TAP1 and TAPBP deficiency on MHC class I expression and immunogenicity.
• To assess the pluripotency, karyotype, and differentiation capacity of the modified hESCs.

Main Methods:

• Utilized transcription activator-like effector nucleases (TALENs) technology for gene editing.
• Generated TAP1-deficient and TAPBP-deficient hESC lines.
• Analyzed MHC class I expression, immunogenicity, pluripotency, karyotype, and differentiation potential.

Main Results:

• TAP1- and TAPBP-deficient hESCs exhibited deficient MHC class I expression on their cell surfaces.
• These modified cells demonstrated reduced immunogenicity compared to wild-type hESCs.
• The hESCs maintained normal pluripotency, karyotypes, and differentiation abilities post-editing.

Conclusions:

• The generation of TAP1- and TAPBP-deficient hESCs is feasible and effective in reducing immunogenicity.
• These hypo-immunogenic hESCs retain essential characteristics for therapeutic applications.
• This research provides a foundation for developing universal cell resources for transplantation therapy.