LBN, University of Montpellier, 34000 Montpellier, France.
Human Health Department, IRSN, French Institute for Radiological Protection and Nuclear Safety, SERAMED, LRMed, 92262 Fontenay-aux-Roses, France.
Int J Mol Sci. 2023 Aug 9;24(16):12594. doi: 10.3390/ijms241612594.
Mesenchymal stem cell secretome or conditioned medium (MSC-CM) is a combination of biomolecules and growth factors in cell culture growth medium, secreted by mesenchymal stem cells (MSCs), and the starting point of several derived products. MSC-CM and its derivatives could be applied after injuries and could mediate most of the beneficial regenerative effects of MSCs without the possible side effects of using MSCs themselves. However, before the clinical application of these promising biopharmaceuticals, several issues such as manufacturing protocols and quality control must be addressed. This review aims to underline the influence of the procedure for conditioned medium production on the quality of the secretome and its derivatives and highlights the questions considering cell sources and donors, cell expansion, cell passage number and confluency, conditioning period, cell culture medium, microenvironment cues, and secretome-derived product purification. A high degree of variability in MSC secretomes is revealed based on these parameters, confirming the need to standardize and optimize protocols. Understanding how bioprocessing and manufacturing conditions interact to determine the quantity, quality, and profile of MSC-CM is essential to the development of good manufacturing practice (GMP)-compliant procedures suitable for replacing mesenchymal stem cells in regenerative medicine.
间充质干细胞分泌组或条件培养基 (MSC-CM) 是细胞培养生长培养基中由间充质干细胞 (MSC) 分泌的生物分子和生长因子的组合，也是几种衍生产品的起点。MSC-CM 及其衍生物可在损伤后应用，并可介导 MSC 大多数有益的再生作用，而没有使用 MSC 本身可能带来的副作用。然而，在这些有前途的生物制药临床应用之前，必须解决几个问题，如制造方案和质量控制。本综述旨在强调产生条件培养基的过程对分泌组及其衍生物质量的影响，并强调考虑细胞来源和供体、细胞扩增、细胞传代数和汇合度、培养期、细胞培养基、微环境线索以及分泌组衍生产品纯化等问题。基于这些参数，揭示了 MSC 分泌组中存在高度的可变性，证实了标准化和优化方案的必要性。了解生物加工和制造条件如何相互作用以确定 MSC-CM 的数量、质量和特征对于开发符合良好生产规范 (GMP) 的程序至关重要，这些程序适用于在再生医学中替代间充质干细胞。
