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骨髓间充质干细胞移植与 NTG-101 分子治疗退行性椎间盘疾病的对比研究。

A comparative study of mesenchymal stem cell transplantation and NTG-101 molecular therapy to treat degenerative disc disease.

机构信息

Notogen Inc., Toronto, Ontario, Canada.

Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

出版信息

Sci Rep. 2021 Jul 20;11(1):14804. doi: 10.1038/s41598-021-94173-w.

DOI:10.1038/s41598-021-94173-w
PMID:34285277
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8292352/
Abstract

Cellular replacement therapy using mesenchymal stem cells (MSCs) and/or the delivery of growth factors are at the forefront of minimally invasive biological treatment options for Degenerative Disc Disease (DDD). In this study, we compared the therapeutic potential of a novel drug candidate, NTG-101 to MSCs, including rat cartilage derived stem cells (rCDSCs), bone marrow stem cells (rBMSCs) and human Umbilical Cord Derived Mesenchymal Stem Cells (hUCMSCs) for the treatment of DDD. We induced DDD using a validated image-guided needle puncture injury in rat-tail IVDs. Ten weeks post-injury, animals were randomized and injected with MSCs, NTG-101 or vehicle. At the end of the study, histological analysis of the IVD-Nucleus Pulposus (NPs) injected with NTG-101 or rCDSCs showed a healthy or mild degenerative phenotype in comparison to vehicle controls. Immunohistochemical analysis revealed strong expression of aggrecan, collagen 2, brachyury and Oct4 in IVD-NPs injected with NTG-101. Our results also demonstrated suppression of inflammation induced p38 and NFκB resulting in inhibition of catabolic genes, but activation of Smad-2/3, Erk-1/2 and Akt-dependent signaling inducing anabolic genes in IVD-NP on treatment with NTG-101. In conclusion, a single injection of NTG-101 into the degenerative disc demonstrated superior benefits compared to stem cell transplantation.

摘要

细胞替代疗法使用间充质干细胞（MSCs）和/或生长因子，是治疗退行性椎间盘疾病（DDD）的微创生物治疗方法的前沿。在这项研究中，我们比较了一种新型候选药物 NTG-101 与 MSCs 的治疗潜力，包括大鼠软骨来源的干细胞（rCDSCs）、骨髓干细胞（rBMSCs）和人脐带间充质干细胞（hUCMSCs）治疗 DDD。我们通过在大鼠尾椎间盘内使用经过验证的图像引导针穿刺损伤来诱导 DDD。损伤后 10 周，动物随机分组并注射 MSCs、NTG-101 或载体。在研究结束时，对注射了 NTG-101 或 rCDSCs 的椎间盘-髓核（NP）进行组织学分析，与载体对照组相比，显示出健康或轻度退行性表型。免疫组织化学分析显示，NTG-101 注射的 NP 中聚集蛋白聚糖、胶原 2、Brachyury 和 Oct4 表达强烈。我们的结果还表明，抑制 p38 和 NFκB 诱导的炎症导致代谢基因的抑制，但激活 Smad-2/3、Erk-1/2 和 Akt 依赖性信号诱导 NP 中合成代谢基因的激活。总之，与干细胞移植相比，将 NTG-101 单次注射到退行性椎间盘具有更好的益处。

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