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.
To cite this abstract in AMA style:Grazia T, Plenter R, Lin C, Gill R, Zamora M. Cardiac Allograft Prolongation by Autologous CD117+ Progenitor Cells Requires CD11b Expression from within the CD117+ Cellular Inoculum [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/cardiac-allograft-prolongation-by-autologous-cd117-progenitor-cells-requires-cd11b-expression-from-within-the-cd117-cellular-inoculum/. Accessed December 1, 2023.
« Back to 2013 American Transplant Congress