Allogeneic peripheral blood precursor cell transplants in rabbits

Area of Science:

• Hematology
• Immunology
• Transplantation Science

Background:

• Peripheral blood precursor cells (PBPC) are increasingly used for transplantation.
• Engraftment across major histocompatibility barriers remains a significant challenge in transplantation.
• Mobilization strategies are crucial for obtaining sufficient PBPC for effective transplantation.

Purpose of the Study:

• To evaluate the efficacy of mobilized peripheral blood precursor cells (PBPC) for transplantation across a major histocompatibility barrier.
• To compare different PBPC infusion methods and their impact on engraftment and survival.
• To investigate the correlation between cell dose (nucleated cells, CFU-GM) and transplantation outcomes.

Main Methods:

• Adult outbred red Burgundy rabbits (donors) and New Zealand white rabbits (recipients) were used.
• Conditioning involved total body irradiation (TBI) and cyclosporine.
• Human recombinant G-CSF mobilized PBPC, which were administered via three different infusion strategies: immediate, cryopreserved/repeated, or multiple fresh infusions.

Main Results:

• Thirteen animals engrafted, with two achieving long-term chimerism.
• Repetitive PBPC infusions resulted in the best median survival (39 days, range 12 to >180 days).
• Survival did not correlate with nucleated cell dose but showed a trend with higher CFU-GM doses (r=0.47, p=0.19).

Conclusions:

• Allogeneic PBPC transplantation (PBPCT) can successfully engraft across major histocompatibility barriers.
• Higher doses of CFU-GM may be advantageous for improving survival in allogeneic PBPCT.
• Additional strategies are necessary to mitigate acute graft-versus-host disease (GvHD).