Transplantation tolerance through mixed chimerism: From allo to xeno

Area of Science:

• Immunology
• Transplantation Biology
• Regenerative Medicine

Background:

• Allogeneic transplantation tolerance is clinically achieved via mixed lymphohematopoietic chimerism.
• Chimerism has been successfully induced in various animal models and humans.
• Mechanisms of tolerance involve deletional and regulatory pathways, varying by model.

Purpose of the Study:

• To review progress in achieving transplantation tolerance, particularly across the xenogeneic pig-to-primate barrier.
• To discuss current strategies for inducing xenograft tolerance involving thymus-based cellular mixtures.
• To highlight the potential of combined approaches for clinical xenograft organ transplantation.

Main Methods:

• Review of established methods for inducing mixed lymphohematopoietic chimerism.
• Analysis of two primary approaches for xenograft tolerance: donor bone marrow administration and vascularized donor thymus transplantation.
• Investigation of cellular engraftment in the thymus for tolerance induction.

Main Results:

• Mixed lymphohematopoietic chimerism is the only current method for clinical allogeneic transplant tolerance.
• Significant progress has been made in xenograft tolerance, though complete success remains elusive.
• Thymus-based strategies show promise for establishing host-donor cell mixtures essential for tolerance.

Conclusions:

• Mixed lymphohematopoietic chimerism is crucial for allogeneic transplant tolerance.
• Thymus-centric approaches are key to advancing xenograft tolerance.
• Combining strategies may enable clinical xenograft organ transplantation.