在使用表达神经保护因子和神经细胞粘附因子的腺病毒载体进行转基因的人类脐血细胞移植后，肌萎缩侧索硬化症的症状改善、延长寿命和持续细胞归巢

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.

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