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藻酸盐/间充质干细胞治疗对大鼠脊髓损伤后轴突生长的刺激作用

Axonal outgrowth stimulation after alginate/mesenchymal stem cell therapy in injured rat spinal cord.

作者信息

Blaško Juraj, Szekiova Eva, Slovinska Lucia, Kafka Jozef, Cizkova Dasa

机构信息

Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovakia;

Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovakia.

出版信息

Acta Neurobiol Exp (Wars). 2017;77(4):337-350.

PMID:29369299
Abstract

Despite strong efforts in the field, spinal cord trauma still belongs among the untreatable neurological conditions at present. Given the complexity of the nervous system, an effective therapy leading to complete recovery has still not been found. One of the potential tools for supporting tissue regeneration may be found in mesenchymal stem cells, which possess anti‑inflammatory and trophic factor‑producing properties. In the context of transplantations, application of degradable biomaterials which could form a supportive environment and scaffold to bridge the lesion area represents another attractive strategy. In the present study, through a combination of these two approaches we applied both alginate hydrogel biomaterial alone or allogenic transplants of MSCs isolated from bone marrow seeded in alginate biomaterial into injured rat spinal cord at three weeks after spinal cord compression performed at Th8‑9 level. Following three‑week survival, using immunohistochemistry we studied axonal growth (GAP‑43 expression) and both microglia (Iba‑1) and astrocyte (GFAP) reactions at the lesion site and in the segments below and above the lesion. To detect functional improvement, during whole survival period we performed behavioral analyses of locomotor abilities using a classical open field test (BBB score) and a Catwalk automated gait analyzing device (Noldus). We found that despite the absence of locomotor improvement, application of both alginate and MSCs caused significant increase in the number of GAP‑43 positive axons.

摘要

尽管该领域付出了巨大努力,但目前脊髓损伤仍属于无法治疗的神经疾病。鉴于神经系统的复杂性,尚未找到能实现完全康复的有效疗法。间充质干细胞可能是支持组织再生的潜在工具之一,其具有抗炎和产生营养因子的特性。在移植方面,应用可降解生物材料形成支持性环境和支架以桥接损伤区域是另一种有吸引力的策略。在本研究中,通过将这两种方法结合,我们在胸8 - 9水平进行脊髓压迫三周后,将单独的藻酸盐水凝胶生物材料或接种于藻酸盐生物材料中的从骨髓分离的间充质干细胞同种异体移植到损伤的大鼠脊髓中。在存活三周后,我们使用免疫组织化学研究了损伤部位以及损伤部位下方和上方节段的轴突生长(GAP - 43表达)以及小胶质细胞(Iba - 1)和星形胶质细胞(GFAP)反应。为了检测功能改善情况,在整个存活期内,我们使用经典旷场试验(BBB评分)和Catwalk自动步态分析装置(Noldus)对运动能力进行了行为分析。我们发现,尽管运动能力没有改善,但藻酸盐和间充质干细胞的应用均导致GAP - 43阳性轴突数量显著增加。

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