CarMeN Laboratory, Institut National de la Santé et de la Recherche Médicale U1060, INRA U1397, Université Lyon 1, INSA Lyon, F-69600 Oullins, France.
VOXCAN, 1 avenue Bourgelat, 69280 Marcy l'Etoile, France.
Nanotheranostics. 2020 Apr 22;4(3):129-141. doi: 10.7150/ntno.45354. eCollection 2020.
: Various types of cell therapies are currently under investigation for the treatment of ischemic stroke patients. To bridge the gap between cell administration and therapeutic outcome, there is a need for non-invasive monitoring of these innovative therapeutic approaches. Spectral photon counting computed tomography (SPCCT) is a new imaging modality that may be suitable for cell tracking. SPCCT is the next generation of clinical CT that allows the selective visualization and quantification of multiple contrast agents. The aims of this study are: (i) to demonstrate the feasibility of using SPCCT to longitudinally monitor and quantify therapeutic cells, i.e. bone marrow-derived M2-polarized macrophages transplanted in rats with brain damage; and (ii) to evaluate the potential of this approach to discriminate M2-polarized macrophages from their encapsulating scaffold. : Twenty one rats received an intralesional transplantation of bone marrow-derived M2-polarized macrophages. In the first set of experiments, cells were labeled with gold nanoparticles and tracked for up to two weeks post-injection in a monocolor study via gold K-edge imaging. In the second set of experiments, the same protocol was repeated for a bicolor study, in which the labeled cells are embedded in iodine nanoparticle-labeled scaffold. The amount of gold in the brain was longitudinally quantified using gold K-edge images reconstructed from SPCCT acquisition. Animals were sacrificed at different time points post-injection, and ICP-OES was used to validate the accuracy of gold quantification from SPCCT imaging. : The feasibility of therapeutic cell tracking was successfully demonstrated in brain-damaged rats with SPCCT imaging. The imaging modality enabled cell monitoring for up to 2 weeks post-injection, in a specific and quantitative manner. Differentiation of labeled cells and their embedding scaffold was also feasible with SPCCT imaging, with a detection limit as low as 5,000 cells in a voxel of 250 × 250 × 250 µm in dimension . : Multicolor SPCCT is an innovative translational imaging tool that allows monitoring and quantification of therapeutic cells and their encapsulating scaffold transplanted in the damaged rat brain.
各种类型的细胞疗法目前正在被研究用于治疗缺血性脑卒中患者。为了缩小细胞治疗与治疗效果之间的差距，需要对这些创新的治疗方法进行非侵入性监测。光谱光子计数计算机断层扫描（SPCCT）是一种新的成像方式，可能适用于细胞示踪。SPCCT 是临床 CT 的下一代技术，可选择性地可视化和量化多种对比剂。本研究的目的是：（i）证明使用 SPCCT 对治疗细胞进行纵向监测和定量的可行性，即骨髓来源的 M2 极化巨噬细胞移植到脑损伤大鼠体内；（ii）评估该方法区分 M2 极化巨噬细胞与其包封支架的潜力。21 只大鼠接受了骨髓来源的 M2 极化巨噬细胞的瘤内移植。在第一组实验中，通过金 K 边成像进行单颜色研究，将细胞用金纳米颗粒标记，并在注射后长达两周内进行追踪。在第二组实验中，重复了相同的方案进行双色研究，其中标记的细胞嵌入碘纳米颗粒标记的支架中。使用从 SPCCT 采集重建的金 K 边图像，对脑内的金量进行纵向定量。在注射后的不同时间点处死动物，并使用 ICP-OES 验证 SPCCT 成像中金定量的准确性。SPCCT 成像成功地证明了治疗性细胞跟踪在脑损伤大鼠中的可行性。该成像方式能够以特异性和定量的方式在注射后长达 2 周内对细胞进行监测。使用 SPCCT 成像也可以区分标记细胞及其包埋支架，检测限低至 250×250×250µm 体素中 5000 个细胞。多色 SPCCT 是一种创新的转化成像工具，允许监测和定量移植到受损大鼠脑内的治疗细胞及其包埋支架。
