Cartilage Regeneration in Osteoarthritic Patients by a Composite of Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronate Hydrogel: Results from a Clinical Trial for Safety and Proof-of-Concept with 7 Years of Extended Follow-Up.
Cartilage Regeneration in Osteoarthritic Patients by a Composite of Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronate Hydrogel: Results from a Clinical Trial for Safety and Proof-of-Concept with 7 Years of Extended Follow-Up.
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DOI：
10.5966/sctm.2016-0157
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发表时间：
2017-02
影响因子：
6
通讯作者：
Park YG
中科院分区：
文献类型：
--
作者：
Park YB;Ha CW;Lee CH;Yoon YC;Park YG
骨关节炎患者关节软骨缺损的再生方法很少。我们的目的是评估由同种异体人脐带血来源的间充质干细胞（hUCB-MSCs）组成的新型药品对关节软骨再生的安全性和有效性。本临床试验入组了Kellgren-Lawrence 3级骨关节炎和国际腕关节修复学会（ICRS）4级软骨缺损患者。将基于干细胞的药品（培养扩增的同种异体hUCB-MSC和透明质酸水凝胶[Cartisem]的复合物）应用于病变部位。根据世界卫生组织的通用毒性标准评估安全性。主要疗效结局是在12周时通过关节镜评估ICRS软骨修复。次要疗效结局是行走疼痛的视觉模拟量表（VAS）评分。在7年的延长随访期间，我们评价了安全性、VAS评分、国际膝关节文献委员会（IKDC）主观评分、磁共振成像（MRI）结果和组织学评价。7名受试者入组。在12周关节镜评价时观察到成熟的修复组织。24周时VAS和IKDC评分均改善。7年随访期间，改善的临床结局稳定。1年时的组织学结果显示透明样软骨。3年时MRI显示再生软骨持续存在。仅观察到5起轻度至中度治疗后出现的不良事件。7年内无骨生成或肿瘤发生病例。这种新型干细胞药物的应用似乎对骨关节炎膝关节的耐久关节软骨再生安全有效。干细胞转化医学2017;6：613-621
Few methods are available to regenerate articular cartilage defects in patients with osteoarthritis. We aimed to assess the safety and efficacy of articular cartilage regeneration by a novel medicinal product composed of allogeneic human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSCs). Patients with Kellgren‐Lawrence grade 3 osteoarthritis and International Cartilage Repair Society (ICRS) grade 4 cartilage defects were enrolled in this clinical trial. The stem cell‐based medicinal product (a composite of culture‐expanded allogeneic hUCB‐MSCs and hyaluronic acid hydrogel [Cartistem]) was applied to the lesion site. Safety was assessed by the World Health Organization common toxicity criteria. The primary efficacy outcome was ICRS cartilage repair assessed by arthroscopy at 12 weeks. The secondary efficacy outcome was visual analog scale (VAS) score for pain on walking. During a 7‐year extended follow‐up, we evaluated safety, VAS score, International Knee Documentation Committee (IKDC) subjective score, magnetic resonance imaging (MRI) findings, and histological evaluations. Seven participants were enrolled. Maturing repair tissue was observed at the 12‐week arthroscopic evaluation. The VAS and IKDC scores were improved at 24 weeks. The improved clinical outcomes were stable over 7 years of follow‐up. The histological findings at 1 year showed hyaline‐like cartilage. MRI at 3 years showed persistence of the regenerated cartilage. Only five mild to moderate treatment‐emergent adverse events were observed. There were no cases of osteogenesis or tumorigenesis over 7 years. The application of this novel stem cell‐based medicinal product appears to be safe and effective for the regeneration of durable articular cartilage in osteoarthritic knees. Stem Cells Translational Medicine 2017;6:613–621