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软骨修复、骨关节炎及细胞外囊泡应用的效力测定考量因素。

Potency Assay Considerations for Cartilage Repair, Osteoarthritis and Use of Extracellular Vesicles.

机构信息

Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.

出版信息

Adv Exp Med Biol. 2023;1420:59-80. doi: 10.1007/978-3-031-30040-0_5.

DOI:10.1007/978-3-031-30040-0_5
PMID:37258784
Abstract

Articular cartilage covers the ends of bones in synovial joints acting as a shock absorber that helps movement of bones. Damage of the articular cartilage needs treatment as it does not repair itself and the damage can progress to osteoarthritis. In osteoarthritis all the joint tissues are involved with characteristic progressive cartilage degradation and inflammation. Autologous chondrocyte implantation is a well-proven cell-based treatment for cartilage defects, but a main downside it that it requires two surgeries. Multipotent, aka mesenchymal stromal cell (MSC)-based cartilage repair has gained attention as it can be used as a one-step treatment. It is proposed that a combination of immunomodulatory and regenerative capacities make MSC attractive for the treatment of osteoarthritis. Furthermore, since part of the paracrine effects of MSCs are attributed to extracellular vesicles (EVs), small membrane enclosed particles secreted by cells, EVs are currently being widely investigated for their potential therapeutic effects. Although MSCs have entered clinical cartilage treatments and EVs are used in in vivo efficacy studies, not much attention has been given to determine their potency and to the development of potency assays. This chapter provides considerations and suggestions for the development of potency assays for the use of MSCs and MSC-EVs for the treatment of cartilage defects and osteoarthritis.

摘要

关节软骨覆盖在滑膜关节的骨端,起到减震器的作用,帮助骨骼运动。关节软骨损伤需要治疗,因为它不会自行修复,而且损伤会进展为骨关节炎。在骨关节炎中,所有的关节组织都受到影响,其特征是进行性软骨降解和炎症。自体软骨细胞移植是一种经过充分验证的基于细胞的软骨缺损治疗方法,但主要缺点是需要进行两次手术。多能性,又名间充质基质细胞(MSC)为基础的软骨修复已经引起了人们的关注,因为它可以作为一种一步治疗方法。有人提出,免疫调节和再生能力的结合使 MSC 成为治疗骨关节炎的有吸引力的选择。此外,由于 MSC 的旁分泌作用部分归因于细胞外囊泡(EVs),即细胞分泌的小膜封闭颗粒,因此 EVs 目前正在广泛研究其潜在的治疗效果。尽管 MSC 已进入临床软骨治疗,EVs 也用于体内疗效研究,但对于确定其效力和开发效力检测方法,并没有给予太多关注。本章提供了关于开发用于治疗软骨缺损和骨关节炎的 MSC 和 MSC-EV 的效力检测方法的考虑和建议。

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本文引用的文献

1
Five-Year Outcome of 1-Stage Cell-Based Cartilage Repair Using Recycled Autologous Chondrons and Allogenic Mesenchymal Stromal Cells: A First-in-Human Clinical Trial.1 期细胞基软骨修复采用自体软骨细胞和同种异体间充质基质细胞的 5 年结果:首例人体临床试验。
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Biological strategies for osteoarthritis: from early diagnosis to treatment.
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Evaluation of biomimetic hyaluronic-based hydrogels with enhanced endogenous cell recruitment and cartilage matrix formation.评价具有增强内源性细胞募集和软骨基质形成能力的仿生透明质酸水凝胶。
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Role of Inflammation and the Immune System in the Progression of Osteoarthritis.炎症和免疫系统在骨关节炎进展中的作用。
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Comparative Effectiveness of Cartilage Repair With Respect to the Minimal Clinically Important Difference.软骨修复的最小临床重要差异的比较效果。
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9
Manufacturing and characterization of extracellular vesicles from umbilical cord-derived mesenchymal stromal cells for clinical testing.脐带间充质干细胞来源的细胞外囊泡的制备及鉴定用于临床检测。
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10
Bone Marrow Mesenchymal Stromal Cell Treatment in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation.骨髓间充质基质细胞治疗骨关节炎患者可整体改善疼痛和症状,并减轻滑膜炎症。
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