BACKGROUND Because the regenerative ability of intervertebral discs (IVDs) is restricted, defects caused by discectomy may induce insufficient tissue repair leading to further IVD degeneration. An acellular bioresorbable biomaterial based on ultra-purified alginate (UPAL) gel was developed to fill the IVD cavity and prevent IVD degeneration. However, an acellular matrix-based strategy may have limitations, particularly in the elderly population, who exhibit low self-repair capability. Therefore, further translational studies involving product combinations, such as UPAL gel plus bone marrow-derived mesenchymal stem cells (BMSCs), are required to evaluate the regenerative effects of BMSCs embedded in UPAL gel on degenerated IVDs. METHODS Rabbit BMSCs and nucleus pulposus cells (NPCs) were co-cultured in a three-dimensional (3D) system in UPAL gel. In addition, rabbit or human BMSCs combined with UPAL gel were implanted into IVDs following partial discectomy in rabbits with degenerated IVDs. FINDINGS Gene expression of NPC markers, growth factors, and extracellular matrix was significantly increased in the NPC and BMSC 3D co-culture compared to that in each 3D mono-culture. In vivo, whereas UPAL gel alone suppressed IVD degeneration as compared to discectomy, the combination of BMSCs and UPAL gel exerted a more potent effect to induce IVD regeneration. Similar IVD regeneration was observed using human BMSCs. INTERPRETATION These findings demonstrate the therapeutic potential of BMSCs combined with UPAL gel as a regenerative strategy following discectomy for degenerated IVDs. FUNDING Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.

中文翻译：

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骨髓间充质干细胞联合超纯化海藻酸盐凝胶作为变性椎间盘切除术后的再生治疗策略。

背景技术由于椎间盘（IVD）的再生能力受到限制，因此由椎间盘切除术引起的缺陷可能引起组织修复不足，从而导致进一步的IVD变性。开发了一种基于超纯藻酸盐（UPAL）凝胶的无细胞生物可吸收生物材料，可填充IVD腔并防止IVD变性。但是，基于脱细胞基质的策略可能会有局限性，特别是在自我修复能力较低的老年人群中。因此，需要进一步的翻译研究，包括产品组合，例如UPAL凝胶加上骨髓源性间充质干细胞（BMSC），以评估UPAL凝胶中嵌入的BMSC对变性IVD的再生作用。方法将兔骨髓间充质干细胞和髓核细胞（NPC）在UPAL凝胶的三维（3D）系统中共培养。另外，在患有退化的IVD的兔子中进行部分椎间盘切除后，将结合UPAL凝胶的兔或人BMSCs植入IVD中。发现与每个3D单培养相比，NPC和BMSC 3D共培养中NPC标记，生长因子和细胞外基质的基因表达显着增加。在体内，虽然与椎间盘切除术相比，单独的UPAL凝胶抑制了IVD变性，但BMSCs和UPAL凝胶的组合发挥了更强的诱导IVD再生的作用。使用人骨髓间充质干细胞观察到类似的IVD再生。解释这些发现表明，椎间盘切除术后退变的IVDs与UPAL凝胶联合使用的BMSC具有治疗潜力。资助日本教育，文化，体育，科学和技术部，