Function of porcine adhesion molecules in a human marrow microenvironment

Area of Science:

• Immunology
• Hematopoiesis
• Xenotransplantation

Background:

• Inducing donor-specific tolerance via bone marrow transplantation is key for solid organ xenografting, potentially reducing immunosuppression needs.
• Successful pig-to-human xenografting requires pig marrow to mature and self-renew within the human marrow environment.
• Adhesion molecule incompatibility, specifically with CD44 and very late antigen (VLA)-4, presents a potential barrier.

Purpose of the Study:

• To investigate the compatibility of CD44 and VLA-4 across the pig-human species barrier.
• To assess the impact of these adhesion molecules on pig and human hematopoiesis in vitro.

Main Methods:

• Utilized in vitro long-term bone marrow cultures.
• Assessed the effects of blocking antibodies against CD44 and VLA-4.
• Measured cell numbers and colony-forming units to evaluate hematopoietic activity.

Main Results:

• Blocking CD44 similarly inhibited hematopoiesis in both pig and human marrow.
• Anti-CD44 monoclonal antibody affected both cellular proliferation and colony-forming activity.
• Blocking VLA-4 significantly inhibited human hematopoietic proliferation but had no effect on pig hematopoiesis, regardless of stromal layer.

Conclusions:

• CD44 and VLA-4 incompatibility is unlikely to impede porcine hematopoiesis in a human marrow environment.
• Differences in VLA-4 utilization between species suggest other interactions may be crucial for porcine hematopoiesis.
• Failure of these other interactions could explain poor porcine hematopoietic cell function in primate marrow microenvironments.