Cardiology Department, HGU Gregorio Marañón. GMP-ATMPs Production Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM). Complutense University, CIBER Cardiovascular (CIBERCV), ISCIII, Madrid, Spain.
Platform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, Spain.
Front Immunol. 2022 Jun 9;13:918565. doi: 10.3389/fimmu.2022.918565. eCollection 2022.
MSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning for enhanced cytokine production, improved cell homing and strengthening of immunomodulatory properties, have been developed but the manufacture and handling of these cells for their use as advanced therapy medicinal products (ATMPs) remains insufficiently studied, and available data are mainly related to non-industrial processes. In the present article, we will review this topic, analyzing current information on the specific regulations, the selection of living donors as well as MSCs from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls for ensuring cell efficiency and safety during all stages of the manual and automatic (bioreactors) manufacturing process, including cryopreservation, the use of cell banks, handling medicines, transport systems of ATMPs, among other related aspects, according to European and US legislation. Our aim is to provide a guide for a better, homogeneous manufacturing of therapeutic cellular products with special reference to MSCs.
间充质干细胞产品及其衍生的细胞外囊泡目前正在作为细胞疗法中的高级生物制剂进行探索，人们对其在未来几年的临床应用寄予厚望。近年来，为提高间充质基质细胞（MSCs）的治疗潜力而设计了各种策略，包括预培养以增强细胞因子产生、改善细胞归巢和增强免疫调节特性，但这些细胞的制造和处理用于先进治疗药物产品（ATMP）的研究还不够充分，并且可用数据主要与非工业过程有关。在本文中，我们将回顾这个主题，分析关于特定法规、作为活供体的选择以及来自不同来源（骨髓、脂肪组织、脐带等）的 MSCs 的当前信息，在手动和自动（生物反应器）制造过程的所有阶段，包括冷冻保存，细胞库的使用、药物处理、ATMP 的运输系统等，都要确保细胞效率和安全性的过程质量控制，这是根据欧洲和美国的法规进行的。我们的目的是根据欧洲和美国的法规，为更好的、同质的治疗细胞产品制造提供指导，特别参考间充质干细胞。
