Department of Biochemical Engineering, Advanced Centre for Biochemical Engineering, University College London, Gower Street, London, United Kingdom; Parent's Guide to Cord Blood Foundation, Brookeville, MD 20833, USA.
Department of Biochemical Engineering, Advanced Centre for Biochemical Engineering, University College London, Gower Street, London, United Kingdom.
Biotechnol Adv. 2020 Dec;45:107636. doi: 10.1016/j.biotechadv.2020.107636. Epub 2020 Sep 25.
Human mesenchymal stem/stromal cells (hMSCs) present a key therapeutic cellular intervention for use in cell and gene therapy (CGT) applications due to their immunomodulatory properties and multi-differentiation capability. Some of the indications where hMSCs have demonstrated pre-clinical or clinical efficacy to improve outcomes are cartilage repair, acute myocardial infarction, graft versus host disease, Crohn's disease and arthritis. The current engineering challenge is to produce hMSCs at an affordable price and at a commercially-relevant scale whilst minimising process variability and manual, human operations. By employing bioreactors and microcarriers (due to the adherent nature of hMSCs), it is expected that production costs would decrease due to improved process monitoring and control leading to better consistency and process efficiency, and enabling economies of scale. This approach will result in off the shelf (allogeneic) hMSC-based products becoming more accessible and affordable. Importantly, cell quality, including potency, must be maintained during the bioreactor manufacturing process. This review aims to examine the various factors to be considered when developing a hMSC manufacturing process using microcarriers and bioreactors and their potential impact on the final product. As concluding remarks, gaps in the current literature and potential future areas of research are also discussed.
人骨髓间充质干细胞（hMSCs）因其免疫调节特性和多向分化能力，成为细胞和基因治疗（CGT）应用中关键的治疗性细胞干预手段。hMSCs 在一些适应症中已经显示出临床前或临床疗效，可以改善疾病结局，这些适应症包括软骨修复、急性心肌梗死、移植物抗宿主病、克罗恩病和关节炎。目前的工程挑战是在降低工艺变异性和减少人工操作的同时，以可承受的价格和商业相关的规模生产 hMSCs。通过使用生物反应器和微载体（由于 hMSCs 的贴壁特性），预计由于改进了工艺监测和控制，生产成本将会降低，从而提高一致性和工艺效率，并实现规模经济。这种方法将使即用型（同种异体）基于 hMSC 的产品更加普及和实惠。重要的是，细胞质量，包括效力，必须在生物反应器制造过程中得到保持。本综述旨在探讨使用微载体和生物反应器开发 hMSC 制造工艺时需要考虑的各种因素，以及它们对最终产品的潜在影响。最后，还讨论了当前文献中的空白和潜在的未来研究领域。
