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.
Export Options
About this article
Cite this article as:
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 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
T Cell Replicative Senescence in Human Aging
Current Pharmaceutical Design Histone Acetylation as a Potential Therapeutic Target in Motor Neuron Degenerative Diseases
Current Pharmaceutical Design Inflammatory Process as a Determinant Factor for the Degeneration of Substantia Nigra Dopaminergic Neurons: Possible Relevance to the Etiology of Parkinsons Disease
Current Medicinal Chemistry - Central Nervous System Agents Activity-dependent Synaptic Plasticity and Metaplasticity in Spinal Motor Networks
Current Pharmaceutical Design The Role of local Insulin-like Growth Factor-1 Isoforms in the Pathophysiology of Skeletal Muscle
Current Genomics A Key Role for Connexin Hemichannels in Spreading Ischemic Brain Injury
Current Drug Targets Cellular Strategies to Combat Protein Misfolding: Intricate Role of Hsp70 in Stress Management
Current Chemical Biology New Hope for the Diagnosis and Therapy of Alzheimers Disease
Protein & Peptide Letters From Bone to Brain: Human Skeletal Stem Cell Therapy for Stroke
Central Nervous System Agents in Medicinal Chemistry P-gp Transporter and its Role in Neurodegenerative Diseases
Current Topics in Medicinal Chemistry A Direct Interaction Between Mitochondrial Proteins and Amyloid-β Peptide and its Significance for the Progression and Treatment of Alzheimer’s Disease
Current Medicinal Chemistry Editorial [Pharmacology and Therapeutic Activity of Purinergic Drugs for Disorders of the Nervous System]
CNS & Neurological Disorders - Drug Targets The Ubiquitin Proteasome System as a Potential Target for the Treatment of Neurodegenerative Diseases
Current Pharmaceutical Design Conference Report: 10th International Summer School of Neurology: Celebrating a Decade of Success: 5th July, 2015 – 9th July, 2015 | Eforie Nord, Romania
CNS & Neurological Disorders - Drug Targets Combating Protein Misfolding and Aggregation by Intracellular Antibodies
Current Molecular Medicine Endotherapia
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry State of the Art Clinical Efficacy and Safety Evaluation of N-Acetylcarnosine Dipeptide Ophthalmic Prodrug. Principles for the Delivery, Self-Bioactivation, Molecular Targets and Interaction with a Highly Evolved Histidyl-Hydrazide Structure in the Treatment and Therapeutic Management of a Group of Sight-Threatening Eye Diseases
Current Clinical Pharmacology siRNA Therapy, Challenges and Underlying Perspectives of Dendrimer as Delivery Vector
Current Pharmaceutical Design The Multifactorial Nature of Alzheimer's Disease for Developing Potential Therapeutics
Current Topics in Medicinal Chemistry Memory-Enhancing Drugs: A Molecular Perspective
Mini-Reviews in Medicinal Chemistry