A new three dimensional biomimetic hydrogel to deliver factors secreted by human mesenchymal stem cells in spinal cord injury
A new three dimensional biomimetic hydrogel to deliver factors secreted by human mesenchymal stem cells in spinal cord injury
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DOI：
10.1016/j.biomaterials.2015.10.024
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发表时间：
2016-01-01
期刊：
影响因子：
14
通讯作者：
Veglianese, Pietro
中科院分区：
文献类型：
--
作者：
Caron, Ilaria;Rossi, Filippo;Veglianese, Pietro
使用人间充质干细胞 (hMSC) 进行干细胞治疗是治疗脊髓损伤 (SCI) 的一种有前途的策略。然而，全身和实质 hMSC 给药都显示出显着的缺点，因为原位干细胞的数量和活力有限。能够封装和维持 hMSC 的生物材料代表了克服这些限制的可行方法，有可能改善干细胞治疗。在这项研究中，我们评估了一种新的基于琼脂糖/卡波姆的水凝胶，它结合了不同的策略来优化 hMSC 的活力、密度和旁分泌因子的传递。具体来说，我们评估了冻干支架上的新加载程序（吸收效应），该程序可减少将 hMSC 封装到水凝胶中时的机械应力。此外，我们将精氨酸-甘氨酸-天冬氨酸 (RGD) 三肽和 3D 细胞外基质沉积相结合，以提高水凝胶中附着和维持健康 hMSC 的能力。此外，通过使用有效引导体内旁分泌因子递送的保鲜膜，改善了从水凝胶向损伤部位的流体扩散。最后，我们证明，本文提出的 hMSC 和仿生水凝胶的改进组合能够显着免疫调节 SCI 小鼠模型中的促炎环境，增加 M2 巨噬细胞群并促进原位促再生环境。 (C) 2015 Elsevier Ltd. 保留所有权利。
Stem cell therapy with human mesenchymal stem cells (hMSCs) represents a promising strategy in spinal cord injury (SCI). However, both systemic and parenchymal hMSCs administrations show significant drawbacks as a limited number and viability of stem cells in situ. Biomaterials able to encapsulate and sustain hMSCs represent a viable approach to overcome these limitations potentially improving the stem cell therapy. In this study, we evaluate a new agarose/carbomer based hydrogel which combines different strategies to optimize hMSCs viability, density and delivery of paracrine factors. Specifically, we evaluate a new loading procedure on a lyophilized scaffold (soaked up effect) that reduces mechanical stress in encapsulating hMSCs into the hydrogel. In addition, we combine arginine-glycine-aspartic acid (RGD) tripeptide and 3D extracellular matrix deposition to increase the capacity to attach and maintain healthy hMSCs within the hydrogel over time. Furthermore, the fluidic diffusion from the hydrogel toward the injury site is improved by using a cling film that oriented efficaciously the delivery of paracrine factors in vivo. Finally, we demonstrate that an improved combination as here proposed of hMSCs and biomimetic hydrogel is able to immunomodulate significantly the pro-inflammatory environment in a SCI mouse model, increasing M2 macrophagic population and promoting a pro-regenerative environment in situ. (C) 2015 Elsevier Ltd. All rights reserved.