Abstract
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.
Keywords: Adeno-virus, amyotrophic lateral sclerosis (ALS), gene-cell therapy, glial cell-derived neuro-trophic factor (GDNF), human umbilical cord blood cell (hUCBC), human umbilical cord blood mono-nuclear cell (hUCB-MC), neural cell adhesion molecule (NCAM), vascular endothelial growth factor (VEGF), viral vector.
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, Andrey Lvovich Zefirov, Andrey Pavlovich Kiyasov and Andras Palotas
Affiliation:
Keywords: Adeno-virus, amyotrophic lateral sclerosis (ALS), gene-cell therapy, glial cell-derived neuro-trophic factor (GDNF), human umbilical cord blood cell (hUCBC), human umbilical cord blood mono-nuclear cell (hUCB-MC), neural cell adhesion molecule (NCAM), vascular endothelial growth factor (VEGF), viral vector.
Abstract: 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:
Islamov Robertovich Rustem, Rizvanov Anatolyevich Albert, Mukhamedyarov Alexandrovich Marat, Salafutdinov Ildusovich Ilnur, Garanina Evgenevna Ekaterina, Fedotova Yuryevna Valeria, Solovyeva Vladimirovna Valeria, Mukhamedshina Olegovna Yana, Safiullov Zufarovich Zufar, Izmailov Alexandrovich Andrey, Guseva Sergeevna Daria, Zefirov Lvovich Andrey, Kiyasov Pavlovich Andrey and Palotas Andras, 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
-
The Journey From Metabolic Profiling to Biomarkers: The Potential of NMR Spectroscopy Based Metabolomics in Neurodegenerative Disease Research
Current Metabolomics Early Features in Frontotemporal Dementia
Current Alzheimer Research Identification of Potent Caspase-3 Inhibitors for Treatment of Multi- Neurodegenerative Diseases Using Pharmacophore Modeling and Docking Approaches
CNS & Neurological Disorders - Drug Targets Novel S-Nitrosothiols Have Potential Therapeutic Uses for Cystic Fibrosis
Current Pharmaceutical Design Chondroitin Sulfate Glycosaminoglycans for CNS Homeostasis-Implications for Material Design
Current Medicinal Chemistry Amyotrophic Lateral Sclerosis: A Genetic Point of View
Current Molecular Medicine Apolipoprotein E4 Serum Concentration for Increased Sensitivity and Specificity of Diagnosis of Drug Treated Alzheimer’s Disease Patients vs. Drug Treated Parkinson’s Disease Patients vs. Age-matched Normal Controls
Current Alzheimer Research Amyotrophic Lateral Sclerosis: From Research to Therapeutic Attempts and Therapeutic Perspectives
Current Medicinal Chemistry Review of Antibiotic and Non-Antibiotic Properties of Beta-lactam Molecules
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Assessing the Effectiveness of a Telemedicine Initiative in Clinical Management of Children Living with HIV/AIDS in Maharashtra, India
Current HIV Research Immunosuppressive Properties of Mesenchymal Stem Cells: Advances and Applications
Current Molecular Medicine Phosphodiesterase-4 Modulation as a Potential Therapeutic for Cognitive Loss in Pathological and Non-Pathological Aging: Possibilities and Pitfalls
Current Pharmaceutical Design Are Cerebral Perfusion and Atrophy Linked in Multiple Sclerosis? Evidence for a Multifactorial Approach to Assess Neurodegeneration
Current Neurovascular Research Vitamin E and All-Cause Mortality: A Meta-Analysis
Current Aging Science Pathophysiology of Transmissible Spongiform Encephalopathies
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Epigenetic and Disease Targets by Polyphenols
Current Pharmaceutical Design Selecting Good ‘Drug-Like’ Properties to Optimize Small Molecule Blood-Brain Barrier Penetration
Current Medicinal Chemistry GABA Receptors: Pharmacological Potential and Pitfalls
Current Pharmaceutical Design Meet Our Editorial Board Member
Current Neuropharmacology Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options
Current Neuropharmacology