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脂肪来源的干细胞提取物可减缓亨廷顿病 R6/2 模型的进展。

Extracts of adipose derived stem cells slows progression in the R6/2 model of Huntington's disease.

机构信息

Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.

出版信息

PLoS One. 2013;8(4):e59438. doi: 10.1371/journal.pone.0059438. Epub 2013 Apr 2.

Abstract

Stem cell therapy is a promising treatment for incurable disorders including Huntington's disease (HD). Adipose-derived stem cell (ASC) is an easily available source of stem cells. Since ASCs can be differentiated into nervous stem cells, it has clinically feasible potential for neurodegenerative disease. In addition, ASCs secrete various anti-apoptotic growth factors, which improve the symptoms of disease from transplanted ASCs. Thus, cell-free extracts of ASCs (ASCs-E) could be a potential candidate for treatment of HD. Here, we investigated effects of ASCs-E on R6/2 HD mouse model and neuronal cells. In R6/2 HD model, injection of ASCs-E improved the performance in Rotarod test. ASCs-E also ameliorated striatal atrophy and mutant huntingtin aggregation in the striatum. In Western blot increased expressions of p-Akt, p-CREB and PGC1α were noted by injection of ASCs-E, when comparing to the R6/2 HD model. Neuro2A neuroblastoma cells treated with ASCs-E showed increased expression of p-CREB and PGC1α. In conclusion, ASCs-E delayed disease progression in animal model of HD by restoring of CREB-PGC1α pathway and could be a potential resource for treatment of HD.

摘要

干细胞疗法是一种有前途的治疗方法,可用于治疗包括亨廷顿病(HD)在内的无法治愈的疾病。脂肪来源的干细胞(ASC)是一种易于获得的干细胞来源。由于 ASC 可以分化为神经干细胞,因此它具有治疗神经退行性疾病的临床可行性。此外,ASC 分泌各种抗细胞凋亡的生长因子,这些因子可改善移植 ASC 引起的疾病症状。因此,ASC 的无细胞提取物(ASC-E)可能是治疗 HD 的潜在候选物。在这里,我们研究了 ASC-E 对 R6/2 HD 小鼠模型和神经元细胞的影响。在 R6/2 HD 模型中,注射 ASC-E 可改善旋转棒测试中的表现。注射 ASC-E 还改善了纹状体中的纹状体萎缩和突变亨廷顿蛋白聚集。Western blot 分析显示,与 R6/2 HD 模型相比,注射 ASC-E 后,p-Akt、p-CREB 和 PGC1α 的表达增加。用 ASC-E 处理的 Neuro2A 神经母细胞瘤细胞显示 p-CREB 和 PGC1α 的表达增加。总之,ASC-E 通过恢复 CREB-PGC1α 通路延缓了 HD 动物模型的疾病进展,可能成为治疗 HD 的潜在资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/3614936/dddfe4d2a59c/pone.0059438.g001.jpg

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