The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the recruitment of MSCs in degenerating intervertebral discs
The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the recruitment of MSCs in degenerating intervertebral discs
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DOI：
10.1016/j.biomaterials.2014.06.017
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发表时间：
2014-09-01
期刊：
影响因子：
14
通讯作者：
Grad, Sibylle
中科院分区：
文献类型：
--
作者：
Pereira, Catarina Leite;Goncalves, Raquel M.;Grad, Sibylle
在活跃人群中，腰椎间盘退变是导致下腰痛和残疾的主要原因。间充质干细胞(MSCs)在水凝胶载体中的移植可以诱导退行性IVD的再生效应。此外，还发现退变的间盘在MSC募集过程中释放出有效的化学诱导剂。基于这些发现，我们推测，一种能够增加IVD中迁移的MSCs数量并为其存活和分化提供合适基质的可注射水凝胶将是理想的。本研究的目的是评价热可逆透明质酸-聚(N-异丙基丙烯酰胺)(HAP)水凝胶作为趋化递送系统在退行性IVD中招募人MSCs的潜力。结果表明，含有基质细胞衍生因子-1(SDF-1)的HAP水凝胶与单独使用HAP或SDF-1溶液处理的椎间盘相比，显著增加了MSCs在去核椎间盘中的迁移数量。释放SDF-1的HAP水凝胶增加了IVD组织中募集的细胞数量及其迁移距离。此外，这种现象依赖于MSC供者的年龄。总之，HAP SDF-1对IVD中干细胞的招募是有效的，从而为基于内源性细胞迁移的再生疗法的发展开辟了新的可能性。(C)2014爱思唯尔有限公司。保留所有权利。
Intervertebral disc (IVD) degeneration is the leading cause of low back pain and disability in the active population. Transplantation of mesenchymal stem cells (MSCs) in a hydrogel carrier can induce regenerative effects in degenerated IVDs. Moreover, it was found that degenerative discs release chemo-attractants effective in MSC recruitment. Based on these findings, we hypothesized that an injectable hydrogel that can enhance the number of migrated MSCs in the IVD and provide a suitable matrix for their survival and differentiation would be ideal. The purpose of this study was to evaluate the potential of a thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel as chemoattractant delivery system to recruit human MSCs in degenerative IVDs. The results demonstrate that HAP hydrogels containing stromal cell derived factor-1 (SDF-1) significantly increased the number of MSCs migrating into nucleotomized discs compared with discs treated with only HAP or SDF-1 in solution. HAP hydrogels releasing SDF-1 enhanced both the number of recruited cells and their migration distance in the IVD tissue. Furthermore, this phenomenon was dependent on MSC donor age. In conclusion, HAP SDF-1 is effective for the recruitment of stem cells in the IVD, thus opening new possibilities for the development of regenerative therapies based on endogenous cell migration. (C) 2014 Elsevier Ltd. All rights reserved.