骨髓抽吸浓缩物联合原位形成可吸收凝胶增强兔椎间盘再生。
Bone Marrow Aspirate Concentrate Combined with in Situ Forming Bioresorbable Gel Enhances Intervertebral Disc Regeneration in Rabbits.
机构信息
Departments of Orthopedic Surgery (D.U., K.Y., T.T., K.U., N.I., and H.S.) and Advanced Medicine for Spine and Spinal Cord Disorders (H.S.), Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Global Station for Soft Matter, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Japan.
出版信息
J Bone Joint Surg Am. 2021 Apr 21;103(8):e31. doi: 10.2106/JBJS.20.00606.
BACKGROUND
The current surgical procedure of choice for intervertebral disc (IVD) herniation is discectomy, which induces postoperative IVD degeneration. Thus, cell-based therapies, as a 1-step simple procedure, are desired because of the poor capacity of IVDs for self-repair. The aim of this study was to investigate the repair efficacy of ultra-purified alginate (UPAL) gels containing bone marrow aspirate concentrate (BMAC) for the treatment of discectomy-associated IVD degeneration in rabbits.
METHODS
The mechanical properties of 3 types of gels-UPAL, UPAL containing bone marrow-derived mesenchymal stem cells (BMSCs), and UPAL containing BMAC-were evaluated. Forty rabbits were assigned to 5 groups: intact control, discectomy (to make the cavity), UPAL (implantation of the UPAL gel after discectomy), BMSCs-UPAL (implantation of a combination of autogenic BMSCs and UPAL gel after discectomy), and BMAC-UPAL (implantation of a combination of BMAC and UPAL gel after discectomy). The gels were implanted at 4 weeks after induction of IVD degeneration. At 4 and 12 weeks, magnetic resonance imaging (MRI) as well as histological and immunohistochemical analyses were performed to analyze IVD degeneration qualitatively and the viability of the implanted cells.
RESULTS
There was no significant difference among the 3 types of gels in terms of the results of unconfined compression tests. The implanted cells survived for 12 weeks. The histological grades of the BMSCs-UPAL (mean and standard deviation, 2.50 ± 0.53; p < 0.001) and BMAC-UPAL (2.75 ± 0.64, p = 0.001) showed them to be more effective in preventing degeneration than UPAL gel alone (3.63 ± 0.52). The effectiveness of BMAC-UPAL was not significantly different from that of BMSCs-UPAL, except with respect to type-II collagen synthesis.
CONCLUSIONS
BMAC-UPAL significantly enhanced the repair of IVD defects created by discectomy. This approach could be an effective therapeutic strategy owing to its simplicity and cost-effectiveness compared with cell therapy using culture-expanded BMSCs.
CLINICAL RELEVANCE
Local administration of the BMAC combined with UPAL gel could be an effective therapeutic strategy to enhance IVD repair after discectomy.
背景
目前治疗椎间盘（IVD）疝的首选手术方法是椎间盘切除术，该手术会导致术后 IVD 退化。因此，由于 IVD 自我修复能力差，人们希望采用细胞疗法作为一种简单的一步法。本研究旨在探讨超纯藻酸盐（UPAL）凝胶中含有骨髓抽吸浓缩物（BMAC）治疗兔椎间盘切除术相关 IVD 退变的修复效果。
方法
评估了 3 种凝胶-UPAL、含骨髓来源间充质干细胞（BMSCs）的 UPAL 和含 BMAC 的 UPAL-的机械性能。将 40 只兔子分为 5 组：完整对照组、椎间盘切除术（制造腔）、UPAL（椎间盘切除术后植入 UPAL 凝胶）、BMSCs-UPAL（椎间盘切除术后植入自体 BMSCs 和 UPAL 凝胶的组合）和 BMAC-UPAL（椎间盘切除术后植入 BMAC 和 UPAL 凝胶的组合）。在 IVD 退变诱导后 4 周植入凝胶。在 4 周和 12 周时，进行磁共振成像（MRI）以及组织学和免疫组织化学分析，以定性分析 IVD 退变和植入细胞的活力。
结果
在无约束压缩试验的结果方面，3 种凝胶之间没有差异。植入细胞存活了 12 周。BMSCs-UPAL（平均值±标准差，2.50±0.53;p<0.001）和 BMAC-UPAL（2.75±0.64;p=0.001）的组织学等级在预防退变方面比 UPAL 凝胶单独使用（3.63±0.52）更有效。BMAC-UPAL 的效果与 BMSCs-UPAL 相似，除了 II 型胶原合成。
结论
BMAC-UPAL 显著增强了椎间盘切除术造成的 IVD 缺陷的修复。与使用培养扩增的 BMSCs 的细胞治疗相比，这种方法由于其简单性和成本效益而可能成为一种有效的治疗策略。
临床意义
局部应用 BMAC 与 UPAL 凝胶相结合可能是增强椎间盘切除术后 IVD 修复的有效治疗策略。
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