Allogeneic mesenchymal stromal cells for cartilage regeneration: A review of in vitro evaluation, clinical experience, and translational opportunities,STEM CELLS Translational Medicine

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Allogeneic mesenchymal stromal cells for cartilage regeneration: A review of in vitro evaluation, clinical experience, and translational opportunities
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2021-08-13 , DOI: 10.1002/sctm.20-0552
Ellison D Aldrich _{1,

2} , Xiaolin Cui ₁ , Caroline A Murphy ₁ , Khoon S Lim ₁ , Gary J Hooper ₁ , C Wayne McIlwraith ₃ , Tim B F Woodfield ₁

Affiliation

The paracrine signaling, immunogenic properties and possible applications of mesenchymal stromal cells (MSCs) for cartilage tissue engineering and regenerative medicine therapies have been investigated through numerous in vitro, animal model and clinical studies. The emerging knowledge largely supports the concept of MSCs as signaling and modulatory cells, exerting their influence through trophic and immune mediation rather than as a cell replacement therapy. The virtues of allogeneic cells as a ready-to-use product with well-defined characteristics of cell surface marker expression, proliferative ability, and differentiation capacity are well established. With clinical applications in mind, a greater focus on allogeneic cell sources is evident, and this review summarizes the latest published and upcoming clinical trials focused on cartilage regeneration adopting allogeneic and autologous cell sources. Moreover, we review the current understanding of immune modulatory mechanisms and the role of trophic factors in articular chondrocyte-MSC interactions that offer feasible targets for evaluating MSC activity in vivo within the intra-articular environment. Furthermore, bringing labeling and tracking techniques to the clinical setting, while inherently challenging, will be extremely informative as clinicians and researchers seek to bolster the case for the safety and efficacy of allogeneic MSCs. We therefore review multiple promising approaches for cell tracking and labeling, including both chimerism studies and imaging-based techniques, that have been widely explored in vitro and in animal models. Understanding the distribution and persistence of transplanted MSCs is necessary to fully realize their potential in cartilage regeneration techniques and tissue engineering applications.

中文翻译：

用于软骨再生的异体间充质基质细胞：体外评估、临床经验和转化机会的综述

通过大量体外、动物模型和临床研究，研究了间充质基质细胞 (MSCs) 在软骨组织工程和再生医学治疗中的旁分泌信号传导、免疫原性特性和可能的应用。新兴知识在很大程度上支持将 MSCs 作为信号传导和调节细胞的概念，通过营养和免疫介导而不是作为细胞替代疗法发挥其影响。同种异体细胞作为一种即用型产品，具有明确的细胞表面标记表达、增殖能力和分化能力特征，其优点已得到充分证实。考虑到临床应用，对同种异体细胞来源的更多关注是显而易见的，这篇综述总结了最新发表和即将进行的临床试验，这些临床试验侧重于采用同种异体和自体细胞来源的软骨再生。此外，我们回顾了目前对免疫调节机制的理解以及营养因子在关节软骨细胞-MSC 相互作用中的作用，这些因素为评估关节内环境中体内 MSC 活性提供了可行的目标。此外，将标记和跟踪技术引入临床环境虽然本身具有挑战性，但随着临床医生和研究人员寻求支持同种异体 MSC 的安全性和有效性的案例，将提供非常丰富的信息。因此，我们回顾了多种有前途的细胞跟踪和标记方法，包括嵌合研究和基于成像的技术，已在体外和动物模型中广泛探索。了解移植的 MSCs 的分布和持久性对于充分发挥其在软骨再生技术和组织工程应用中的潜力是必要的。

更新日期：2021-08-13

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