Chung Yi-Hsiu, Ho Yi-Pei, Farn Shiou-Shiow, Tsai Wei-Cheng, Li Zhi-Xiang, Lin Tzou-Yien, Weng Chi-Chang
Department of Medical Research and Development, Research Division, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan; Healthy Aging Research Center, Chang GungUniversity, Taoyuan, Taiwan.
Biomed J. 2024 Oct;47(5):100721. doi: 10.1016/j.bj.2024.100721. Epub 2024 Apr 16.
Extracellular vesicles derived from human umbilical cord-derived mesenchymal stem cells (UCMSC-EVs) have been postulated to have therapeutic potential for various diseases. However, the biodistribution and pharmacokinetics of these vesicles are still unclear. For a better understanding of the in vivo properties of UCMSC-EVs, in the present study, these vesicles were first radiolabeled with Technetium-99m (Tc-UCMSC-EVs) and evaluated using in vivo single photon emission computed tomography (SPECT) imaging and biodistribution experiments. SPECT images demonstrated that the liver and spleen tissues mainly took up the Tc-UCMSC-EVs. The biodistribution study observed slight uptake in the thyroid and stomach, indicating that Tc-UCMSC-EVs was stable at 24 h in vivo. The pharmacokinetic analyses of the blood half-life demonstrated the quick distribution phase (0.85 ± 0.28 min) and elimination phase (25.22 ± 20.76 min) in mice. This study provides a convenient and efficient method for Tc-UCMSC-EVs preparation without disturbing their properties. In conclusion, the biodistribution, quick elimination, and suitable stability in vivo of Tc-UCMSC-EVs were quantified by the noninvasive imaging and pharmacokinetic analyses, which provides useful information for indication selection, dosage protocol design, and toxicity assessment in future applications.
源自人脐带间充质干细胞的细胞外囊泡(UCMSC-EVs)被认为对多种疾病具有治疗潜力。然而,这些囊泡的生物分布和药代动力学仍不清楚。为了更好地了解UCMSC-EVs的体内特性,在本研究中,首先用锝-99m对这些囊泡进行放射性标记(Tc-UCMSC-EVs),并使用体内单光子发射计算机断层扫描(SPECT)成像和生物分布实验进行评估。SPECT图像显示,肝脏和脾脏组织主要摄取了Tc-UCMSC-EVs。生物分布研究观察到甲状腺和胃部有轻微摄取,表明Tc-UCMSC-EVs在体内24小时内是稳定的。血液半衰期的药代动力学分析表明,小鼠体内存在快速分布阶段(0.85±0.28分钟)和消除阶段(25.22±20.76分钟)。本研究提供了一种方便有效的Tc-UCMSC-EVs制备方法,且不会干扰其特性。总之,通过无创成像和药代动力学分析对Tc-UCMSC-EVs的生物分布、快速消除和体内合适的稳定性进行了量化,这为未来应用中的适应症选择、剂量方案设计和毒性评估提供了有用信息。