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Injectable Hydrogel Combined with Nucleus Pulposus-Derived Mesenchymal Stem Cells for the Treatment of Degenerative Intervertebral Disc in Rats

机译:可注射水凝胶结合核瓜骨衍生的间充质干细胞,用于治疗大鼠退化椎间盘

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摘要

Stem cell-based tissue engineering in treating intervertebral disc (IVD) degeneration is promising. An appropriate cell scaffold can maintain the viability and function of transplanted cells. Injectable hydrogel has the potential to be an appropriate cell scaffold as it can mimic the condition of the natural extracellular matrix (ECM) of nucleus pulposus (NP) and provide binding sites for cells. This study was aimed at investigating the effect of injectable hydrogel-loaded NP-derived mesenchymal stem cells (NPMSC) for the treatment of IVD degeneration (IDD) in rats. In this study, we selected injectable 3D-RGD peptide-modified polysaccharide hydrogel as a cell transplantation scaffold. In vitro, the biocompatibility, microstructure, and induced differentiation effect on NPMSC of the hydrogel were studied. In vivo, the regenerative effect of hydrogel-loaded NPMSC on degenerated NP in a rat model was evaluated. The results showed that NPMSC was biocompatible and able to induce differentiation in hydrogel in vivo. The disc height index (almost 87%) and MRI index (3313.83±227.79) of the hydrogel-loaded NPMSC group were significantly higher than those of other groups at 8 weeks after injection. Histological staining and immunofluorescence showed that the hydrogel-loaded NPMSC also partly restored the structure and ECM content of degenerated NP after 8 weeks. Moreover, the hydrogel could support long-term NPMSC survival and decrease cell apoptosis rate of the rat IVD. In conclusion, injectable hydrogel-loaded NPMSC transplantation can delay the level of IDD and promote the regeneration of the degenerative IVD in the rat model.
机译:干在治疗椎间盘细胞为基础的组织工程(IVD)退变是有希望的。合适的细胞支架可以保持活力和移植细胞的功能。可注射的水凝胶必须是适当的细胞的支架,因为它可以模仿髓核(NP)的天然细胞外基质(ECM)的条件,并提供用于结合位点的细胞的潜力。本研究旨在调查注射水凝胶装载NP-间充质干细胞(NPMSC)对大鼠IVD变性(IDD)的治疗效果。在这项研究中,我们选择了可注射的3D-RGD肽改性的多糖的水凝胶作为细胞移植支架。在体外,生物相容性,微结构,以及所述水凝胶的NPMSC诱导分化作用进行了研究。在体内,在简并NP在大鼠模型中的水凝胶加载NPMSC的再生效果进行了评价。结果表明,NPMSC是生物相容的并且能诱导分化在体内水凝胶。椎间盘高度指数(几乎87%)和水凝胶加载NPMSC组的MRI指数(3313.83±227.79)比其他组在8周注射后显著更高。组织学染色和免疫荧光结果表明,水凝胶加载NPMSC也部分地在8周后恢复退化NP的结构和ECM的内容。此外,水凝胶可以支持大鼠IVD的长期NPMSC生存和减少细胞凋亡率。最后,注射水凝胶加载NPMSC移植可延缓IDD的水平,促进在大鼠模型中的退化性IVD的再生。

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