Lui Pauline Po Yee, Leung Yung Tim
Center for Neuromusculoskeletal Restorative Medicine, Hong Kong SAR, China.
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
Pharmaceutics. 2022 Aug 12;14(8):1684. doi: 10.3390/pharmaceutics14081684.
Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) have shown potential for the treatment of tendon and ligament injuries. This approach can eliminate the need to transplant live cells to the human body, thereby reducing issues related to the maintenance of cell viability and stability and potential erroneous differentiation of transplanted cells to bone or tumor. Despite these advantages, there are practical issues that need to be considered for successful clinical application of MSC-EV-based products in the treatment of tendon and ligament injuries. This review aims to discuss the general and tissue-specific considerations for manufacturing MSC-EVs for clinical translation. Specifically, we will discuss Good Manufacturing Practice (GMP)-compliant manufacturing and quality control (parent cell source, culture conditions, concentration method, quantity, identity, purity and impurities, sterility, potency, reproducibility, storage and formulation), as well as safety and efficacy issues. Special considerations for applying MSC-EVs, such as their compatibility with arthroscopy for the treatment of tendon and ligament injuries, are also highlighted.
源自间充质基质细胞（MSC）的细胞外囊泡（EV）已显示出治疗肌腱和韧带损伤的潜力。这种方法可以消除向人体移植活细胞的需求，从而减少与维持细胞活力和稳定性以及移植细胞向骨或肿瘤错误分化相关的问题。尽管有这些优点，但在基于MSC-EV的产品成功临床应用于治疗肌腱和韧带损伤方面，仍有一些实际问题需要考虑。本综述旨在讨论用于临床转化的MSC-EV制造的一般和组织特异性考量。具体而言，我们将讨论符合良好生产规范（GMP）的制造和质量控制（亲本细胞来源、培养条件、浓缩方法、数量、身份、纯度和杂质、无菌性、效力、可重复性、储存和制剂），以及安全性和有效性问题。还强调了应用MSC-EV的特殊考量，例如它们与关节镜检查治疗肌腱和韧带损伤的兼容性。
