■近年来,外泌体已被证明可用于治疗许多疾病。然而,由于外泌体缺乏统一的质量控制标准,外泌体的安全性仍然是一个有待解决的问题,特别是现在越来越多的外泌体被用于临床试验,其非临床安全性评价尤为重要。然而,目前没有外泌体的安全性评价标准。因此,这项研究将参考治疗性生物制品的评价标准,采用非人灵长类动物从一般药理学和免疫毒性方面评价人脐带间充质干细胞外泌体的非临床安全性,旨在建立外泌体的安全性评价体系,为今后外泌体的临床应用提供参考。
■将来源于人脐带间充质干细胞的3.85×1012外泌体静脉注射到食蟹猴体内。一般临床情况的变化,血液学,免疫球蛋白,Th1/Th2细胞因子,T淋巴细胞和B淋巴细胞,注射前和注射后14天内观察免疫器官。
■结果表明,外泌体对一般临床状况没有明显的病理影响,血,凝血功能,器官系数,免疫球蛋白,Th1/Th2细胞因子,淋巴细胞,主要器官,和主要免疫器官(脾脏,胸腺,食蟹猴的骨髓)。然而,外泌体组粒细胞-巨噬细胞集落数量明显高于对照组。
■总而言之,一般药理和免疫毒性结果显示,注射3.85×1012个外泌体对食蟹猴可能无明显不良反应。这个剂量的外泌体对于治疗是相对安全的,为外泌体的非临床安全性评价提供了基础研究,为外泌体的未来临床应用提供了可靠的研究依据。
UNASSIGNED: In recent years, exosomes have been proved to be used to treat many diseases. However, due to the lack of uniform quality control standards for exosomes, the safety of exosomes is still a problem to be solved, especially now more and more exosomes are used in clinical trials, and its non-clinical safety evaluation is particularly important. However, there is no safety evaluation standard for exosomes at present. Therefore, this study will refer to the evaluation criteria of therapeutic biological products, adopt non-human primates to evaluate the non-clinical safety of human umbilical cord mesenchymal stem cell exosomes from the general pharmacology and immunotoxicity, aiming at establishing a safety evaluation system of exosomes and providing reference for the clinical application of exosomes in the future.
UNASSIGNED: 3.85 × 1012 exosomes derived from human umbilical cord mesenchymal stem cells were injected into cynomolgus monkeys intravenously. The changes of general clinical conditions, hematology, immunoglobulin, Th1/Th2 cytokines, T lymphocytes and B lymphocytes, and immune organs were observed before and within 14 days after injection.
UNASSIGNED: The results showed that exosomes did not have obvious pathological effects on the general clinical conditions, blood, coagulation function, organ coefficient, immunoglobulin, Th1/Th2 cytokines, lymphocytes, major organs, and major immune organs (spleen, thymus, bone marrow) of cynomolgus monkeys. However, the number of granulocyte-macrophage colonies in exosomes group was significantly higher than that in control group.
UNASSIGNED: To sum up, the general pharmacological results and immunotoxicity results showed that the injection of 3.85 × 1012 exosomes may have no obvious adverse reactions to cynomolgus monkeys. This dose of exosomes is relatively safe for treatment, which provides basis research for non-clinical safety evaluation of exosomes and provides reliable research basis for future clinical application of exosomes.