Abstract 15550: Impact of PET Imaging to Visualize Activated Macrophages in Immune Rejection of Allogenic iPS Derived Cardiac Myocytes in Mice

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Introduction: Transplantation of allogeneic cells inevitably induce activated macrophage-related host immune response, which would limit therapeutic effects. Importantly, monitoring magnitude of the immune response is poorly established in the allogeneic cell transplantation therapy for the heart. Hypothesis: In this study, we hypothesized that [18F]-DPA-714-PET imaging may visualize activated macrophages accumulated to the host heart after transplantation of allogeneic induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM). Methods: iPSC-CM cell-sheets of C57BL/6 mice origin were generated by the thermoresponsive dish and transplanted over the surface of the left ventricle (LV) of C57BL/6 mice as a syngeneic cell-transplant model (Group sTx), or Balb/c mice as an allogeneic one (Group aTx). The mice were examined by [18F]-DPA-714-PET to assess maximum standardized uptake value (SUVmax) ratio (A/S ratio) calculated by SUVmax in the anterior and septal wall of the LV. In addition, expression of factors associated with immune rejection was assessed by RT-PCR and the significance of immune rejection was evaluated by Immunochemical staining of CD3 or CD68 positive cell. Results: A/S ratio was comparable in all groups at 1 day (aTx: 1.19±0.05, sTx: 1.16±0.03, sham: 1.20±0.03, p=0.34), though higher in the aTx group than the other groups at 7 day (aTx: 1.38±0.03, p<0.01, sTx: 1.18±0.04, sham: 1.25±0.09) after the cell transplantation. In addition, the expression of IL-2 and MCP-1 of the heart tissue were higher in the aTx group than the other groups at 7 day (aTx: 31.4±3.8, p<0.01, sTx: 1.5±1.2, sham: 2.3±0.9 and aTx: 30.8±12.7, p<0.01, sTx: 4.0±3.4, sham: 5.5±2.0). Furthermore, in the immunochemical histology, the percentages of CD3 and CD68 positive cells were also higher in the aTx group than the other groups at 7day. Conclusions: Accumulation of activated macrophages were identified in the LV surface more intensely after the allogeneic iPSC-CM transplantation than the syngeneic or sham one by the [18F]-DPA-714-PET imaging, warranting that PET imaging may be applicable in clinical setting of the allogeneic cell transplantation therapy to monitor magnitude of host immune response.