Ma Zhiteng, Kahan Riley, Xia Jianping, Wu Mengxi, Lu Brandon, David Emeraghi, He Ye, Chen Ying, Liu Jessica F, Liu Mingyuan, Xu Haojun, Stempora Linda, Abraham Nader, Zhong Ruoyu, Yang Kaichun, Jin Ke, Li Ke, Zhang Min, Wu Qian, Barbas Andrew, Kwun Jean, Lee Luke P, Huang Tony Jun, Chambers Eileen T
Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA.
Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Sci Adv. 2025 Sep 5;11(36):eady3262. doi: 10.1126/sciadv.ady3262.
Antibody-mediated rejection is a leading cause of allograft failure and mortality in pediatric solid organ transplant recipients. Current apheresis systems require large blood volumes and are primarily designed for adults, making them unsuitable for children and small animals. These systems often indiscriminately remove both harmful and protective antibodies, increasing the risk of complications such as life-threatening infections. To address this critical need, we developed acoustofluidic-based system for targeted antibody removal in transplantation (A-START). A-START is engineered to handle small blood volumes and has demonstrated efficacy in preclinical small animal trials. In a sensitized rodent skin transplantation model, A-START only demands 240 microliters of blood, selectively removing donor-specific alloantibodies (DSAs) while preserving protective antibodies, such as tetanus antibodies. A-START retains ~95% of beneficial antibodies and achieves a 60% improvement in DSA removal compared to conventional methods. These findings highlight the transformative potential of A-START as a promising, reliable, scalable solution for improving outcomes in pediatric transplantation and treating antibody-mediated diseases.
抗体介导的排斥反应是小儿实体器官移植受者同种异体移植失败和死亡的主要原因。目前的血液分离系统需要大量血液,且主要是为成年人设计的,因此不适用于儿童和小动物。这些系统常常不加区分地清除有害抗体和保护性抗体,增加了诸如危及生命的感染等并发症的风险。为满足这一关键需求,我们开发了基于声流体的移植靶向抗体清除系统(A-START)。A-START经过设计,可处理少量血液,并且已在临床前小动物试验中证明了其有效性。在致敏啮齿动物皮肤移植模型中,A-START仅需240微升血液,可选择性清除供体特异性同种异体抗体(DSA),同时保留保护性抗体,如破伤风抗体。与传统方法相比,A-START保留了约95%的有益抗体,并且在DSA清除方面提高了60%。这些发现凸显了A-START作为一种有前景、可靠且可扩展的解决方案,在改善小儿移植结局和治疗抗体介导疾病方面的变革潜力。