Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA; Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA; School of Postgraduate Studies, Royal College of Surgeons in Ireland, Dublin, Ireland.
Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Biomaterials. 2022 Jul;286:121544. doi: 10.1016/j.biomaterials.2022.121544. Epub 2022 May 6.
Osteoarthritis (OA) is a progressive degenerative joint disease which results in chronic degeneration of articular cartilage and sclerosis of bone. While tendons and ligaments may heal to a limited extent, articular cartilage has poor intrinsic regenerative potential, and critical-sized bone defects and pathological fractures cannot regenerate spontaneously. OA represents a significant burden of disease globally, affecting 240 million people in the world. The objective of tissue engineering is to recapitulate the natural healing cascade and developmental process by transplanting stromal and progenitor cells which can act directly or indirectly. As the ultimate goal of regenerative medicine is to avoid in vitro expansion of cells and its associated complications, the adipose-derived stromal cell (ASC) is an attractive progenitor cell for tissue engineering for treatment of OA. While clinical studies are still in their infancy, ASCs together with novel scaffold materials represent promising treatment options for patients suffering from OA. How ASCs exert their regenerative potential is a topic of debate, whereby it may be a result of direct differentiation of ASCs into the desired regenerating tissue, and/or through paracrine activity. With the advancement of material science, it is increasingly possible to enhance engraftment of ASCs through the use of biomaterials or to direct progenitor cell fate by activating biophysical signals through designed material microstructures. There are currently over 180 completed or ongoing registered early stage clinical trials involving ASCs, with 17 completed studies reviewed herein detailing the use of ASCs in OA. In order for ASC therapy to become an "off-the-shelf" option for treating OA, several strategies are currently being explored such as ASC cryopreservation and use of allogeneic ASCs. Newer approaches, such as exosome therapy, allow for the use of acellular ASC-derived therapies and are also currently the focus of ongoing investigations.
骨关节炎（OA）是一种进行性退行性关节疾病，导致关节软骨慢性退变和骨硬化。虽然肌腱和韧带可以在一定程度上愈合，但关节软骨内在再生潜力差，临界尺寸的骨缺损和病理性骨折不能自发再生。OA 在全球范围内是一种严重的疾病负担，影响全球 2.4 亿人。组织工程的目标是通过移植能够直接或间接发挥作用的基质和祖细胞来重现自然愈合级联和发育过程。由于再生医学的最终目标是避免细胞的体外扩增及其相关并发症，脂肪来源的基质细胞（ASC）是治疗 OA 的组织工程中一种有吸引力的祖细胞。虽然临床研究仍处于起步阶段，但 ASC 与新型支架材料一起为 OA 患者提供了有前途的治疗选择。ASC 如何发挥其再生潜力是一个有争议的话题，它可能是 ASC 直接分化为所需再生组织的结果，和/或通过旁分泌活性。随着材料科学的进步，通过使用生物材料增强 ASC 的植入或通过设计材料微观结构激活生物物理信号来指导祖细胞命运，越来越有可能实现。目前有超过 180 项已完成或正在进行的早期临床试验涉及 ASC，本文综述了 17 项已完成的研究，详细介绍了 ASC 在 OA 中的应用。为了使 ASC 治疗成为治疗 OA 的“现成”选择，目前正在探索几种策略，如 ASC 冷冻保存和使用同种异体 ASC。较新的方法，如外泌体治疗，允许使用无细胞 ASC 衍生疗法，也是目前正在进行的研究的重点。
