Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: a preliminary study on biglycan-deficient murine model of chronic disc degeneration.
Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: a preliminary study on biglycan-deficient murine model of chronic disc degeneration.
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DOI：
10.1186/s13075-014-0457-5
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发表时间：
2014-10-08
影响因子：
4.9
通讯作者：
Parati E
中科院分区：
文献类型：
--
作者：
Marfia G;Campanella R;Navone SE;Zucca I;Scotti A;Figini M;Di Vito C;Alessandri G;Riboni L;Parati E
双糖蛋白聚糖是椎间盘细胞外基质（IVD）的重要蛋白聚糖，其随年龄的减少与IVD退变有关。双糖蛋白聚糖缺陷（Bgn-/0）小鼠缺乏这种蛋白质，并随着衰老而发生自发的IVD变性，因此代表了一种有价值的体内模型，可用于人类进行性IVD变性疗法的初步研究。本研究的目的是评估Bgn−/0小鼠模型中脂肪源性基质细胞（ADSC）植入物的可能有益作用。为了评估ADSC植入的有效性，在16个月大时，当小鼠表现出严重和完全的IVD变性时，在7特斯拉磁共振成像（7 TMRI）和组织学上都很明显，向Bgn−/0小鼠椎间盘内（L1-L2）注射8 × 104 ADSC。通过7 TMRI分析评估安慰剂和ADSC治疗的Bgn-/0小鼠，直至移植后12周。然后处死小鼠，并通过组织学和免疫组织化学分析植入的椎间盘中是否存在人细胞以及IVD区域中双糖蛋白聚糖和聚集蛋白聚糖的表达。在体内治疗后，7 TMRI显示接受ADSC的小鼠椎间盘内的信号强度明显增加，而安慰剂治疗没有显示任何变化。超微结构分析表明，人ADSC的生存发生在注射的椎间盘植入后长达12周。这些细胞获得双糖蛋白聚糖的阳性表达，并且该蛋白聚糖特异性地定位于人细胞中。此外，ADSC处理导致聚集蛋白聚糖组织水平的显著增加。总的来说，这项工作表明，ADSC植入Bgn−/0小鼠退变的椎间盘改善了椎间盘损伤，促进了双糖蛋白聚糖的新表达和聚集蛋白聚糖水平的增加。这表明ADSC植入物在治疗慢性退行性椎间盘疾病中具有潜在的益处，并促进了该领域的进一步研究。
Biglycan is an important proteoglycan of the extracellular matrix of intervertebral disc (IVD), and its decrease with aging has been correlated with IVD degeneration. Biglycan deficient (Bgn−/0) mice lack this protein and undergo spontaneous IVD degeneration with aging, thus representing a valuable in vivo model for preliminary studies on therapies for human progressive IVD degeneration. The purpose of the present study was to assess the possible beneficial effects of adipose-derived stromal cells (ADSCs) implants in the Bgn−/0 mouse model. To evaluate ADSC implant efficacy, Bgn−/0 mice were intradiscally (L1-L2) injected with 8x104 ADSCs at 16 months old, when mice exhibit severe and complete IVD degeneration, evident on both 7Tesla Magnetic Resonance Imaging (7TMRI) and histology. Placebo and ADSCs treated Bgn−/0 mice were assessed by 7TMRI analysis up to 12 weeks post-transplantation. Mice were then sacrificed and implanted discs were analyzed by histology and immunohistochemistry for the presence of human cells and for the expression of biglycan and aggrecan in the IVD area. After in vivo treatment, 7TMRI revealed evident increase in signal intensity within the discs of mice that received ADSCs, while placebo treatment did not show any variation. Ultrastructural analyses demonstrated that human ADSC survival occurred in the injected discs up to 12 weeks after implant. These cells acquired a positive expression for biglycan, and this proteoglycan was specifically localized in human cells. Moreover, ADSC treatment resulted in a significant increase of aggrecan tissue levels. Overall, this work demonstrates that ADSC implant into degenerated disc of Bgn−/0 mice ameliorates disc damage, promotes new expression of biglycan and increased levels of aggrecan. This suggests a potential benefit of ADSC implant in the treatment of chronic degenerative disc disease and prompts further studies in this field.
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通讯作者：
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