Combination of a peptide-modified gellan gum hydrogel with cell therapy in a lumbar spinal cord injury animal model
Combination of a peptide-modified gellan gum hydrogel with cell therapy in a lumbar spinal cord injury animal model
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DOI：
10.1016/j.biomaterials.2016.07.019
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发表时间：
2016-10-01
期刊：
影响因子：
14
通讯作者：
Salgado, Antonio J.
中科院分区：
文献类型：
--
作者：
Gomes, Eduardo D.;Mendes, Sofia S.;Salgado, Antonio J.
脊髓损伤（SCI）是一种高度失能的疾病，目前仍无法治愈。目前的临床方法主要是基于姑息治疗，所以有必要找到可能的治疗SCI。由于细胞如脂肪组织来源的基质/干细胞（ASC）或嗅鞘细胞（OEC）的治疗潜力，细胞移植被认为具有很大的期望。两者都是可获得的来源，并提出了积极的旁分泌和细胞间的相互作用，以前由我们的小组报告。此外，生物材料如水凝胶已被应用于SCI修复，并取得了可喜的成果。我们建议将GRGDS修饰的结冷胶水凝胶与ASC和OEC结合联合收割机以促进SCI再生。在体外，与对照相比，ASC和OEC可以在GG-GRGDS水凝胶内共培养，诱导更稳健的神经突生长。在半切SCI大鼠模型中的体内实验显示，与对照组（SCI）和单独的水凝胶组（GG-GRGDS）相比，给予封装在GG-GRGDS水凝胶中的ASC和OEC导致显著的运动改善。这伴随着炎性细胞和星形胶质细胞浸润减少，神经丝强度增加。这些结果表明通过将ASC和OEC包封在基于GG-GRGDS的水凝胶中诱导的明显增益。(C)2016爱思唯尔有限公司版权所有
Spinal Cord Injury (SCI) is a highly incapacitating condition for which there is still no cure. Current clinical approaches are mainly based on palliative care, so there is a need to find possible treatments to SCI. Cellular transplantation is regarded with great expectation due to the therapeutic potential of cells such as Adipose tissue-derived Stromal/Stem Cells (ASCs) or Olfactory Ensheathing Cells (OECs). Both are accessible sources and present positive paracrine and cell-to-cell interactions, previously reported by our group. Additionally, biomaterials such as hydrogels have been applied in SCI repair with promising results. We propose to combine a GRGDS-modified gellan gum hydrogel with ASCs and OECs in order to promote SCI regeneration. In vitro, ASCs and OECs could be co-cultured within GG-GRGDS hydrogels inducing a more robust neurite outgrowth when compared to controls. In vivo experiments in a hemisection SCI rat model revealed that the administration of ASCs and OECs encapsulated in a GG-GRGDS hydrogel led to significant motor improvements when compared to both control (SCI) and hydrogel alone (GG-GRGDS) groups. This was accompanied by a decreased infiltration of inflammatory cells and astrocytes, and by an increased intensity of neurofilament. These results suggest evident gains induced by the encapsulation of ASCs and OECs in GG-GRGDS based hydrogels. (C) 2016 Elsevier Ltd. All rights reserved.