Intervertebral disc degeneration is a cascade of cellular, structural, and biomechanical changes that is strongly implicated as a cause of low-back pain. Current treatment strategies have poor long-term efficacy as they seek only to alleviate symptoms without preserving or restoring native tissue structure and function. The objective of this study was to evaluate the efficacy of a combined triple interpenetrating network hydrogel (comprising dextran, chitosan, and teleostean) and mesenchymal stem cell (MSC) therapy targeting moderate-severity disc degeneration in a clinically relevant goat model. Degeneration was induced in lumbar discs of 10 large frame goats by injection of chondroitinase ABC. After 12 weeks, degenerate discs were treated by injection of either hydrogel alone or hydrogel seeded with allogeneic, bone marrow-derived MSCs. Untreated healthy and degenerate discs served as controls, and animals were euthanized 2 weeks after treatment. Discs exhibited a significant loss of disc height 12 weeks after degeneration was induced. Two weeks after treatment, discs that received the combined hydrogel and MSC injection exhibited a significant, 10% improvement in disc height index, as well as improvements in histological condition. Discs that were treated with hydrogel alone exhibited reduced tumor necrosis factor-α expression in the nucleus pulposus (NP). Microcomputed tomography imaging revealed that the hydrogel remained localized to the central NP region of all treated discs after 2 weeks of unrestricted activity. These encouraging findings motivate further, longer term studies of therapeutic efficacy of hydrogel and MSC injections in this large animal model.

中文翻译：

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水凝胶和间充质干细胞联合治疗山羊中度椎间盘退变。

椎间盘退变是一系列细胞、结构和生物力学变化，与腰痛的原因密切相关。目前的治疗策略长期疗效不佳，因为它们仅寻求缓解症状而不保留或恢复天然组织结构和功能。本研究的目的是评估三重互穿网络水凝胶（包含葡聚糖、壳聚糖和硬骨鱼）和间充质干细胞 (MSC) 联合疗法在临床相关山羊模型中针对中度严重椎间盘退变的疗效。通过注射软骨素酶 ABC 在 10 只大型山羊的腰椎间盘中诱导退化。12 周后，通过注射单独的水凝胶或接种同种异体骨髓来源的 MSCs 的水凝胶来治疗退化的椎间盘。未经处理的健康和退化的椎间盘作为对照，处理后 2 周对动物实施安乐死。在诱导变性后 12 周，椎间盘表现出椎间盘高度的显着下降。治疗两周后，接受水凝胶和 MSC 联合注射的椎间盘表现出椎间盘高度指数显着改善 10%，以及组织学状况的改善。单独用水凝胶处理的椎间盘在髓核 (NP) 中表现出降低的肿瘤坏死因子-α 表达。显微计算机断层扫描成像显示，在 2 周无限制活动后，水凝胶仍定位于所有治疗椎间盘的中央 NP 区域。这些令人鼓舞的发现激发了对这种大型动物模型中水凝胶和 MSC 注射治疗效果的进一步长期研究。