72: Recipient Based Strategies for Improved Transplant Efficiency: CD26 Inhibitor Treated and CD26 -/- Recipient Mice Exhibit Increased Short-Term Homing and Long-Term Engraftment of Hematopoietic Stem and Progenitor Cells

Abstract

Introduction: Through the use of CD26 inhibitors and CD26 deficient mice (CD26-/-), we have previously generated data suggesting that suppression of CD26/DPPIV activity on the transplant donor cell population could potentially be utilized clinically as a method of increasing transplant efficiency. However, the clinical importance of the transplant recipient should not to be overlooked. We therefore investigated whether inhibition or loss of CD26 activity in the recipient would have an effect on hematopoietic stem cell transplantation utilizing an in vivo congenic mouse model of transplantation. Methods: The short-term homing and long-term engraftment of BoyJ donor cells (expressing CD45.1+) into lethally irradiated control C57BL/6, CD26 inhibitor (Diprotin A) treated C57BL/6, or CD26-/- mice (expressing CD45.2+) was monitored by flow cytometric analysis of the bone marrow and peripheral blood at 24 hours and 6 months post-transplant. Results: Twenty-four hours post-transplant of 20 × 106 BoyJ mononuclear cells, we observed 8.85 ± 0.58%, 10.69 ± 1.01%, and 12.45 ± 1.33% donor derived Sca-1+lin- cells in the bone marrow of recipient mice for control, Diprotin A treated, and CD26-/- recipient mice respectively. As compared to control mice, this represents a 20.8% increase (p = 0.01) with CD26 inhibitor treatment and a 40.7% increase (p ≤ 0.05) resulting from the use of a CD26-/- recipient in short-term homing (N = 5 mice per group). Six months post-transplant of 1 × 105 BoyJ mononuclear cells, we observed 39.90 ± 4.38%, 70.22 ± 3.72%, and 92.51 ± 1.04% donor contribution to hematopoiesis in the peripheral blood of control, Diprotin A treated, and CD26-/- recipient mice respectively. This represents a 76.0% increase (p ≤ 0.01) with CD26 inhibitor treatment and a 131.9% increase (p ≤ 0.01) as a result of the CD26-/- recipient in long-term engraftment as compared to control recipient mice (N = 14 mice per group). Conclusions: These results provide pre-clinical evidence of the importance of CD26 expression within the transplant recipient with regard to regulating hematopoietic stem cell homing and engraftment. Our results also support the potential use of CD26 inhibitors to treat transplant patients during hematopoietic stem cell transplantation as a method of improving transplant efficiency.