Educell Ltd., Prevale 9, 1236, Trzin, Slovenia.
Department of Orthopedic Surgery, University Medical Centre Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia.
Tissue Eng Regen Med. 2020 Jun;17(3):375-386. doi: 10.1007/s13770-020-00253-9. Epub 2020 Apr 23.
Osteochondral injury is a very common orthopaedic pathology, mainly affecting young, active population, with limited current treatment options. Herein we are presenting cellular and early clinical data of a patient series treated for chronic osteochondral lesions in the knee with a filter-based intra-operative bone marrow aspirate (BMA) separation device.
Fifteen patients with chronic knee osteochondral lesions (60% females, 19-59 years) were included in this prospective case series. Filtered BMA (f-BMA), containing mesenchymal stem/stromal cells (MSCs), was combined with a biomimetic collagen-hydroxyapatite scaffold (CHAS) and implanted into the site of the lesion. Harvested BMA and post-separation f-BMA were analysed for blood cell counts, flow cytometry, and fibroblast colony forming units (CFU-Fs). Patients were followed for serious adverse events and graft failures. Clinical evaluation was assessed using the knee injury and osteoarthritis outcome score (KOOS). In 8 patients a magnetic resonance imaging (MRI)/arthroscopy were performed.
Cell suspension contained 0.027% CD271 CD45 7-AAD cells, 0.15% CD73 CD90 CD105 cells and 0.0012% CFU-Fs of all nucleated cells with 86% viability. Filtration process resulted in 12.8 (4.0-40.8) fold enrichment in terms of CFU-F content in comparison to initial BMA. No serious adverse events related directly to the osteochondral treatment were reported. After an average follow-up of 20 months (14-25) all KOOS subscales (Symptoms/Pain/Daily activities/Sport and recreation/Quality of life) increased significantly from pre-operative 55/56/67/30/30 to post-operative 73/76/79/51/52 (p values < 0.05), respectively. MRI or arthroscopic evaluation revealed nearly normal to normal overall International Cartilage Repair Society assessment in 7/8 patients.
The filter-based BMA separation procedure significantly increased the frequency of mesenchymal stem/stromal cells (MSCs), however their concentration was not increased. The clinical evaluation revealed high safety profile of the treatment and resulted in improved clinical status of the patients.
骨软骨损伤是一种非常常见的骨科病理，主要影响年轻、活跃的人群，目前的治疗选择有限。在此，我们介绍了一系列使用基于过滤器的术中骨髓抽吸（BMA）分离装置治疗膝关节慢性骨软骨损伤的患者的细胞和早期临床数据。
本前瞻性病例系列研究纳入了 15 名患有慢性膝关节骨软骨损伤的患者（女性占 60%，年龄 19-59 岁）。将含有间充质干细胞（MSCs）的过滤 BMA（f-BMA）与仿生胶原-羟基磷灰石支架（CHAS）相结合，并植入病变部位。采集 BMA 和分离后的 f-BMA 进行血细胞计数、流式细胞术和成纤维细胞集落形成单位（CFU-F）分析。患者随访严重不良事件和移植物失败情况。临床评估采用膝关节损伤和骨关节炎结果评分（KOOS）。8 例患者行磁共振成像（MRI）/关节镜检查。
细胞悬液中包含 0.027%的 CD271+CD45-7-AAD 细胞、0.15%的 CD73+CD90+CD105 细胞和 0.0012%的所有有核细胞中的 CFU-F，细胞活力为 86%。与初始 BMA 相比，过滤过程使 CFU-F 含量富集了 12.8（4.0-40.8）倍。未报告与骨软骨治疗直接相关的严重不良事件。平均随访 20 个月（14-25 个月）后，所有 KOOS 亚量表（症状/疼痛/日常活动/运动和娱乐/生活质量）均从术前的 55/56/67/30/30 显著增加到术后的 73/76/79/51/52（p 值均<0.05）。8 例患者中有 7 例 MRI 或关节镜评估显示整体国际软骨修复学会评估接近正常或正常。
基于过滤器的 BMA 分离程序显著增加了间充质干细胞（MSCs）的频率，但浓度没有增加。临床评估显示该治疗方法具有较高的安全性，并改善了患者的临床状况。
