Diminished immune cell adhesion in hypoimmune ICAM-1 knockout human pluripotent stem cells

Area of Science:

• Regenerative Medicine
• Immunology
• Gene Editing

Background:

• Gene editing in human pluripotent stem cells offers potential for immune-evasive regenerative therapies.
• Current strategies primarily target adaptive immunity, neglecting innate immune cells crucial in early graft rejection.
• Intercellular Adhesion Molecule-1 (ICAM-1) is identified as a key target involved in both adaptive and innate immune responses.

Purpose of the Study:

• To investigate ICAM-1 as a novel hypoimmune target for gene-edited pluripotent stem cell therapies.
• To evaluate the impact of ICAM-1 knockout on immune cell binding and graft rejection.
• To assess the efficacy of combining ICAM-1 knockout with existing hypoimmune strategies.

Main Methods:

• CRISPR/Cas9 gene editing was used to knock out ICAM-1 in human pluripotent stem cells.
• Assays were performed to measure immune cell binding to ICAM-1 edited cells.
• In vitro assays assessed T cell proliferation and activation.
• In vivo studies utilized NeoThy humanized mice to evaluate graft retention and protection.

Main Results:

• ICAM-1 knockout significantly diminished the binding of multiple immune cell types to stem cell therapies.
• ICAM-1 knockout resulted in reduced T cell proliferation and activation in vitro.
• Grafts with ICAM-1 knockout showed improved in vivo retention and protection from immune attack.
• Combining ICAM-1 knockout with existing hypoimmune edits further prevented immune cell binding.

Conclusions:

• Targeting ICAM-1 is a promising strategy to create hypoimmune regenerative therapies.
• ICAM-1 knockout effectively reduces both innate and adaptive immune cell interactions.
• This approach holds potential for improving transplantation outcomes in cardiovascular diseases and beyond.