Modulating the red cell membrane to produce universal/stealth donor red cells suitable for transfusion

Area of Science:

• Blood banking and transfusion medicine
• Biotechnology and biomaterials
• Immunology

Background:

• Universal group O donor red blood cells (RBCs) are crucial for transfusions.
• Current methods for producing group O RBCs from other blood groups have limitations.

Purpose of the Study:

• To review and compare two main approaches for generating universal group O donor RBCs: enzyme-converted (ECO) RBCs and polyethylene glycol (PEG)-modified RBCs.
• To assess the challenges and potential of these methods for clinical application.

Main Methods:

• Enzyme-based conversion: Cleavage of terminal immunodominant sugars from RBC membranes using specific enzymes to create ECO RBCs.
• Chemical modification: Bonding polyethylene glycol (PEG) to RBCs to create 'stealth' PEG-RBCs that mask antigens.

Main Results:

• ECO RBCs from group B donors have been successfully transfused; however, group A RBC conversion presents difficulties, and polyclonal antibodies remain a cross-matching challenge.
• Initial 'stealth' PEG-RBCs showed in vitro serological issues and potential reduced in vivo survival. While improved, recent findings indicate PEG immunogenicity and antibody-mediated reduced survival of PEG-RBCs and pegylated proteins.

Conclusions:

• Enzyme-converted group O RBCs show promise but require further refinement to overcome cross-matching challenges with polyclonal antibodies.
• Polyethylene glycol-modified RBCs face significant hurdles due to immunogenicity and potential for reduced in vivo survival, questioning their future as 'stealth' RBCs.