Automated Large-Scale Production of Paclitaxel Loaded Mesenchymal Stromal Cells for Cell Therapy Applications
Automated Large-Scale Production of Paclitaxel Loaded Mesenchymal Stromal Cells for Cell Therapy Applications
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DOI：
10.3390/pharmaceutics12050411
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发表时间：
2020-05-01
期刊：
影响因子：
5.4
通讯作者：
Pessina, Augusto
中科院分区：
文献类型：
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作者：
Lisini, Daniela;Nava, Sara;Pessina, Augusto
作为先进治疗药品（ATMP）制备的间充质基质细胞（MSC）已广泛用于治疗不同的疾病。最新进展涉及使用间充质干细胞作为分子载体（包括化疗药物）的可能性。利用其固有的归巢特性，间充质干细胞可以改善药物在疾病区域的定位。然而，对于细胞治疗应用，需要大量装载药物的间充质干细胞。我们在这里研究使用封闭的生物反应器系统生产大量符合良好生产规范（GMP）的装载化疗药物紫杉醇（MSC-PTX）的间充质干细胞的可能性。从 13 个脂肪组织吸脂物中获得细胞。所有样品都在数量/活力、形态、生长动力学和免疫表型方面进行了表征。还评估了 MSC 内化 PTX 的能力以及 MSC-PTX 的体外抗增殖活性。结果表明，我们的方法可以在一周内大规模扩增细胞； MSCs-PTX尽管与MSCs的形态不同，但在活力、粘附能力和表型方面表现出MSCs的典型特征。此外，MSCs表现出内化PTX并最终杀死癌细胞、抑制体外肿瘤系增殖的能力。总之，我们的结果首次证明可以在短时间内获得大量负载 PTX 的 MSC，用于治疗肿瘤疾病患者的临床试验。
Mesenchymal stromal cells (MSCs) prepared as advanced therapies medicinal products (ATMPs) have been widely used for the treatment of different diseases. The latest developments concern the possibility to use MSCs as carrier of molecules, including chemotherapeutic drugs. Taking advantage of their intrinsic homing feature, MSCs may improve drugs localization in the disease area. However, for cell therapy applications, a significant number of MSCs loaded with the drug is required. We here investigate the possibility to produce a large amount of Good Manufacturing Practice (GMP)-compliant MSCs loaded with the chemotherapeutic drug Paclitaxel (MSCs-PTX), using a closed bioreactor system. Cells were obtained starting from 13 adipose tissue lipoaspirates. All samples were characterized in terms of number/viability, morphology, growth kinetics, and immunophenotype. The ability of MSCs to internalize PTX as well as the antiproliferative activity of the MSCs-PTX in vitro was also assessed. The results demonstrate that our approach allows a large scale expansion of cells within a week; the MSCs-PTX, despite a different morphology from MSCs, displayed the typical features of MSCs in terms of viability, adhesion capacity, and phenotype. In addition, MSCs showed the ability to internalize PTX and finally to kill cancer cells, inhibiting the proliferation of tumor lines in vitro. In summary our results demonstrate for the first time that it is possible to obtain, in a short time, large amounts of MSCs loaded with PTX to be used in clinical trials for the treatment of patients with oncological diseases.