Sagaradze G D, Grigorieva O A, Efimenko A Yu, Chaplenko A A, Suslina S N, Sysoeva V Yu, Kalinina N I, Akopyan Zh A, Tkachuk V A
Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russia; OOO "Gene and Cell Therapy", Moscow, Russia.
OOO "Gene and Cell Therapy", Moscow, Russia.
Biomed Khim. 2015 Nov-Dec;61(6):750-9. doi: 10.18097/PBMC20156106750.
Regenerative medicine approaches, such as replacement of damaged tissue by ex vivo manufactured constructions or stimulation of endogenous reparative and regenerative processes to treat different diseases, are actively developing. One of the major tools for regenerative medicine are stem and progenitor cells, including multipotent mesenchymal stem/stromal cells (MSC). Because the paracrine action of bioactive factors secreted by MSC is considered as a main mechanism underlying MSC regenerative effects, application of MSC extracellular secreted products could be a promising approach to stimulate tissue regeneration; it also has some advantages compared to the injection of the cells themselves. However, because of the complexity of composition and multiplicity of mechanisms of action distinguished the medicinal products based on bioactive factors secreted by human MSC from the most of pharmaceuticals, it is important to develop the approaches to their standardization and quality control. In the current study, based on the literature data and guidelines as well as on our own experimental results, we provided rationalization for nomenclature and methods of quality control for the complex of extracellular products secreted by human adipose-derived MSC on key indicators, such as "Identification", "Specific activity" and "Biological safety". Developed approaches were tested on the samples of conditioned media contained products secreted by MSC isolated from subcutaneous adipose tissue of 30 donors. This strategy for the standardization of innovative medicinal products and biomaterials based on the bioactive extracellular factors secreted by human MSC could be applicable for a wide range of bioactive complex products, produced using the different types of stem and progenitor cells.
再生医学方法，如通过体外制造的构建体替代受损组织或刺激内源性修复和再生过程来治疗不同疾病，正在积极发展。再生医学的主要工具之一是干细胞和祖细胞，包括多能间充质干/基质细胞（MSC）。由于MSC分泌的生物活性因子的旁分泌作用被认为是MSC再生作用的主要机制，应用MSC细胞外分泌产物可能是刺激组织再生的一种有前途的方法；与注射细胞本身相比，它也有一些优势。然而，由于基于人MSC分泌的生物活性因子的药品在成分复杂性和作用机制多样性方面与大多数药物不同，因此开发其标准化和质量控制方法很重要。在本研究中，基于文献数据、指南以及我们自己的实验结果，我们针对人脂肪来源的MSC分泌的细胞外产物复合物在关键指标（如“鉴定”、“比活性”和“生物安全性”）方面的命名和质量控制方法提供了合理化建议。所开发的方法在来自30名供体皮下脂肪组织分离的MSC分泌产物的条件培养基样本上进行了测试。这种基于人MSC分泌的生物活性细胞外因子对创新药品和生物材料进行标准化的策略可能适用于使用不同类型干细胞和祖细胞生产的广泛生物活性复合产品。
