Center for Engineering in Medicine and Surgical Services, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Shriners Hospitals for Children, Boston, Massachusetts, USA.
Center for Engineering in Medicine and Surgical Services, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Shriners Hospitals for Children, Boston, Massachusetts, USA; Harvard Stem Cell Institute, Cambridge, Massachusetts, USA; Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA.
Cytotherapy. 2017 Dec;19(12):1537-1545. doi: 10.1016/j.jcyt.2017.08.003. Epub 2017 Sep 13.
Cell transplants offer a new opportunity to deliver therapies with novel and complex mechanisms of action. Understanding the pharmacology of cell transplants is important to deliver this new therapy effectively. Currently, however, there are limited techniques to easily track cells after intravenous administration due to the dispersion of the graft throughout the entire body.
We herein developed an engineered cell system that secretes a luciferase enzyme to sensitively detect cell transplants independent of their locale by a simple blood test. We specifically studied a unique feature of cell transplant pharmacology-namely, immune clearance-using mesenchymal stromal cells (MSCs) as a proof-of-concept cell therapy. MSCs are a clinically relevant cell therapy that has been explored in several disease indications due to their innate properties of altering an immune response.
Using this engineered reporter, we observed specific sensitivity of cell therapy exposure to the preparation of cells, cytolysis of MSCs in an allogeneic setting and a NK cell-mediated destruction of MSCs in an autologous setting.
Our cellular tracking method has broader implications at large for assessing in vivo kinetics of various other cell therapies.
细胞移植为提供具有新颖和复杂作用机制的治疗方法提供了新的机会。了解细胞移植的药理学对于有效地提供这种新疗法非常重要。然而，由于移植物在整个身体中的分散，目前只有有限的技术可以在静脉给药后轻松跟踪细胞。
我们在此开发了一种工程细胞系统，该系统分泌一种荧光素酶酶，通过简单的血液测试，独立于其位置灵敏地检测细胞移植。我们特别研究了细胞移植药理学的一个独特特征，即免疫清除，使用间充质基质细胞 (MSC) 作为概念验证细胞治疗。MSC 是一种临床相关的细胞治疗方法，由于其改变免疫反应的固有特性，已在多种疾病适应症中进行了探索。
使用这种工程报告基因，我们观察到细胞治疗暴露于细胞制剂、同种异体环境中 MSC 的细胞溶解以及 NK 细胞介导的 MSC 自体破坏的特定敏感性。
我们的细胞跟踪方法对于评估各种其他细胞治疗的体内动力学具有更广泛的意义。
