摘要
肌萎缩侧索硬化症 (ALS) 是一种以运动神经元逐步丧失和骨骼肌麻痹为特征的不可治愈的、慢性的、致命的神经退行性疾病。重新激活功能失调区域正在被使用各种方法进行认真研究。在此我们提出一个新型基因-细胞构想,旨在重振惰性结构和功能。经编码人类VEGF、GDNF 和/或 NCAM 基因的腺病毒载体转导的人类脐血细胞 (hUCBCs) 被植入转基因ALS鼠模型中。行为表现(旷场和抓力测试)的明显改善和寿命增加在经NCAM-VEGF 或 NCAM-GDNF共转染细胞处理的啮齿动物中被观察到。活跃的转基因表达被发现于交付转基因hUCBCs后10周的ALS鼠的脊髓中,并且细胞可被检测于移植后的5个月。我们的基因-细胞治疗模型实现了ALS显著的症状控制和延长寿命。异体移植细胞难以置信的存活率也被观测到,无任何免疫低下。这些结果表明工程化hUCBCs或许可为ALS提供有效的基因-细胞治疗。
关键词: 腺病毒,肌萎缩侧索硬化症 (ALS),基因-细胞治疗,胶质细胞源性神经营养因子 (GDNF),人类脐带血细胞 (hUCBC),人类脐带血单核细胞 (hUCB-MC),神经细胞粘附分子 (NCAM),血管内皮生长因子 (VEGF),病毒载体。
Current Gene Therapy
Title:Symptomatic Improvement, Increased Life-Span and Sustained Cell Homing in Amyotrophic Lateral Sclerosis After Transplantation of Human Umbilical Cord Blood Cells Genetically Modified with Adeno-Viral Vectors Expressing a Neuro-Protective Factor and a Neural Cell Adhesion Molecule
Volume: 15 Issue: 3
Author(s): Rustem Robertovich Islamov, Albert Anatolyevich Rizvanov, Marat Alexandrovich Mukhamedyarov, , Ilnur Ildusovich Salafutdinov, Ekaterina Evgenevna Garanina, Valeria Yuryevna Fedotova, Valeria Vladimirovna Solovyeva, Yana Olegovna Mukhamedshina, Zufar Zufarovich Safiullov, Andrey Alexandrovich Izmailov, Daria Sergeevna Guseva and Andrey Lvovich Zefirov, Andrey Pavlovich Kiyasov and Andras Palotas
Affiliation:
关键词: 腺病毒,肌萎缩侧索硬化症 (ALS),基因-细胞治疗,胶质细胞源性神经营养因子 (GDNF),人类脐带血细胞 (hUCBC),人类脐带血单核细胞 (hUCB-MC),神经细胞粘附分子 (NCAM),血管内皮生长因子 (VEGF),病毒载体。
摘要: Amyotrophic lateral sclerosis (ALS) is an incurable, chronic, fatal neuro-degenerative disease characterized by progressive loss of moto-neurons and paralysis of skeletal muscles. Reactivating dysfunctional areas is under earnest investigation utilizing various approaches. Here we present an innovative gene-cell construct aimed at reviving inert structure and function. Human umbilical cord blood cells (hUCBCs) transduced with adeno-viral vectors encoding human VEGF, GDNF and/or NCAM genes were transplanted into transgenic ALS mice models. Significant improvement in behavioral performance (open-field and grip-strength tests), as well as increased life-span was observed in rodents treated with NCAM-VEGF or NCAM-GDNF co-transfected cells. Active trans-gene expression was found in the spinal cord of ALS mice 10 weeks after delivering genetically modified hUCBCs, and cells were detectable even 5 months following transplantation. Our gene-cell therapy model yielded prominent symptomatic control and prolonged life-time in ALS. Incredible survivability of xeno-transpanted cells was also observed without any immune-suppression. These results suggest that engineered hUCBCs may offer effective gene-cell therapy in ALS.
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Rustem Robertovich Islamov, Albert Anatolyevich Rizvanov, Marat Alexandrovich Mukhamedyarov , , Ilnur Ildusovich Salafutdinov, Ekaterina Evgenevna Garanina, Valeria Yuryevna Fedotova, Valeria Vladimirovna Solovyeva , Yana Olegovna Mukhamedshina, Zufar Zufarovich Safiullov, Andrey Alexandrovich Izmailov, Daria Sergeevna Guseva and Andrey Lvovich Zefirov, Andrey Pavlovich Kiyasov and Andras Palotas , Symptomatic Improvement, Increased Life-Span and Sustained Cell Homing in Amyotrophic Lateral Sclerosis After Transplantation of Human Umbilical Cord Blood Cells Genetically Modified with Adeno-Viral Vectors Expressing a Neuro-Protective Factor and a Neural Cell Adhesion Molecule, Current Gene Therapy 2015; 15 (3) . https://dx.doi.org/10.2174/1566523215666150126122317
DOI https://dx.doi.org/10.2174/1566523215666150126122317 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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