Purpose: Published studies demonstrate significant cardiac allograft prolongation with autologous CD117⁺ progenitor cell (PC) therapy as well as differential engraftment of the allograft and related immune tissues with CD117⁺ PC. However, it is unclear what the signal for differential engraftment of CD117⁺ PC is as well as what CD117-derived cellular population(s) is (are) responsible for allograft prolongation. Consequently, we sought to answer these 2 questions.

Methods and Results: We found dramatic differential engraftment of CD117⁺ PC vs. CD117^– control cells in BALB/c ⇒B6 heart allograft recipients that received either 10⁷ GFP-tagged CD117⁺ PC or CD117^– control cells on day +1 with subsequent harvest for FACS analysis on day +4. Interestingly, syngeneic (B6⇒B6) heart transplant studies (isolated ischemia reperfusion injury/IRI) show no significant differential engraftment under otherwise identical experimental conditions. Differentiation studies utilizing 10⁷ GFP-tagged CD117⁺ PC given day +1 demonstrate that the vast majority CD117-derived cells are CD11b⁺ by day +4 post transplantation (94% of the allograft, 65% of the spleen, and 83% of the draining lymph node group). Based on this result, we performed CD11b depletion studies utilizing CD11b-DTR mice as CD117⁺ PC donors with subsequent treatment of the allograft recipient with diphtheria toxin. Results demonstrate abrogation of allograft prolongation with removal of CD11b⁺ cells from within the autologous CD117⁺ PC inoculum (Fig 1).

Conclusion: Results demonstrate that the primary signal for differential engraftment of CD117⁺ PC is acute allo-immunity and not IRI and that a majority of CD117⁺ PC-derived cells express CD11b by day +4 post transplantation. Importantly, CD11b expression from within the CD117⁺ PC inoculum is required for cardiac allograft prolongation – suggesting a potential critical role by an 'innate' hematopoietic cellular population.

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