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• W4255574854 abstract "Introduction: Cardiac allograft vasculopathy (CAV) is the major limiting factor for the long-term survival of heart transplant recipients. Current immunosuppression regimens, including calcineurin inhibitor (CNI), for CAV remain suboptimal. Burixafor, a small molecule CXC motif chemokine receptor 4 (CXCR4) antagonist, has been demonstrated to mobilize immunomodulatory mesenchymal stem cells. We evaluated the efficacy of burixafor on top of mycophenolate mofetil (MMF)-based immunosuppressants as CNI-free treatment for controlling CAV in a swine model of heart transplantation. Methods: Minipigs received MMF and corticosteroid (control) combined with burixafor as a two-dose (burixafor2D) or two-dose plus booster injections (burixafor2D + B) schedule. The efficacy endpoints were the survival estimate for graft loss, freedom from first acute rejection, and the severity of intimal hyperplasia. Results: A total of 22 minipigs were included: 10 in the control, 7 in the burixafor2D, and 5 in the burixafor2D + B. Survival at postoperative day150 was 0% for control, 28.5% for burixafor2D, and 60% for burixafor2D + B (p = 0.0845 for control vs burixafor2D; p = 0.0088 control vs burixafor2D + B). Freedom from acute rejection was improved in the burixafor2D + B (median 136 days) compared with the burixafor2D (median 76 days) and the control (median 33.5 days) groups (p = 0.0209 for control vs burixafor2D + B). Incidence rate of acute rejection (0.033 for controls, 0.009 for burixafor2D; odds ratio = 0.03, p = 0.002) and severity of intimal hyperplasia (61.7 ± 15.3% for control; 46.8 ± 5.7% for burixafor2D, p = 0.0097) was significantly reduced by burixafor2D, consistent with less dense cell infiltrates in the graft vessels (7165 ± 2473 cells/mm2 for control; 4741 ± 1745 cells/mm2 for burixafor2D, p = 0.0017). Tests including measurements of blood urea nitrogen, creatinine, aspartate aminotransferase, and alanine aminotransferase, did not show a significant difference between burixafor2D + B and the controls. Conclusion: CNI-free immunosuppression based on CXCR4 antagonist plus MMF and corticosteroid is feasible in the pre-clinical large animal. Escalating doses of burixafor conferred a survival benefit and delayed onset of acute rejection." @default.
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• W4255574854 date "2017-05-01" @default.
• W4255574854 modified "2023-10-16" @default.
• W4255574854 title "CXCR4 Antagonist Reduces Incidence of Acute Rejection and Controls Cardiac Allograft Vasculopathy in Swine Heart Transplant Receiving Mycophenolate-Based Immunosuppressive Regimen" @default.
• W4255574854 doi "https://doi.org/10.1097/01.tp.0000520403.00087.c4" @default.
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