Analysis of the Efficiency of Gene-Cell Therapy in Transgenic Mice with Amyotrophic Lateral Sclerosis Phenotype

Mukhamedyarov, Marat A.; Rizvanov, Albert A.; Safiullov, Zufar Z.; Izmailov, Andrei; Sharifullina, G. A.; Solovieva, V. V.; Fedotova, V. Yu.; Салафутдинов, И. И.; Черенкова, Е. Е.; Bashirov, Farid Vagizovich; Калигин, М. С.; Абдулхаков, С. Р.; Шмаров, М. М.; Logunov, Denis Y.; Naroditsky, Boris S.; Kiyasov, Andrey P.; Зефиров, А. Л.; Islamov, R. R.

doi:10.1007/s10517-013-1999-2

Cited by 5 publications

(4 citation statements)

References 13 publications

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“…Two weeks before cell transplantation, mice were trained to perform two types of behavioral tests: open field and grip strength. In the open field test, mouse was placed to the commercially obtained arena (Otkrytaya Nauka, Russia) for 3 minutes and the number of crossed lines (horizontal activity), vertical stands (vertical activity), and the number of explored holes in arena floor (exploration activity) were analyzed as described previously [11]. Grip strength test was performed on the next day after open field testing.…”

Section: Behavioral Testsmentioning

confidence: 99%

“…Variability of therapeutic genes, gene vectors, types of stem cells as well as possible different combinations between recombinant genes and cells selected for gene delivery in our studies keep us as pioneers in development of gene-cell approaches for ALS treatment [11][12][13][14]. Here we present new gene-cell constructs for ALS treatment, based on human umbilical cord blood mono-nuclear cells (hUCBMCs) and adenoviral vectors encoding human VEGF, GDNF and NCAM genes in different combinations.…”

Section: Introductionmentioning

confidence: 99%

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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

Islamov

Rizvanov²,

Mukhamedyarov³

et al. 2015

CGT

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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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Section: Behavioral Testsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Islamov

Rizvanov²,

Mukhamedyarov³

et al. 2015

CGT

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“…In addition, intraspinal injection of human UCB derived cells in G93A transgenic mouse model of ALS at early stages increased survival, which resulted in significant improvements in motor performance and astrogliosis in the spinal cord [73]. Recently, gene-cell therapy using UCB cells based on genetically modified mononuclear cells expressing vascular endothelial growth factor (VEGF) and reporter green fluorescent protein (EGFP) efficiently improved the parameters of motor and explorative activity, grip strength, and survival of SOD1 G93A transgenic mice having ALS [74]. …”

Section: Disease or Lesion Specific Use Of Ucbmentioning

confidence: 99%

Application of Umbilical Cord Blood Derived Stem Cells in Diseases of the Nervous System

Achyut

Varma

Arbab

2014

J Stem Cell Res Ther

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Umbilical cord blood (UCB) derived multipotent stem cells are capable of giving rise hematopoietic, epithelial, endothelial and neural progenitor cells. Thus suggested to significantly improve graft-versus-host disease and represent the distinctive therapeutic option for several malignant and non-malignant diseases. Recent advances in strategies to isolate, expand and shorten the timing of UCB stem cells engraftment have tremendously improved the efficacy of transplantations. Nervous system has limited regenerative potential in disease conditions such as cancer, neurodegeneration, stroke, and several neural injuries. This review focuses on application of UCB derived stem/progenitor cells in aforementioned pathological conditions. We have discussed the possible attempts to make use of UCB therapies to generate neural cells and tissues with developmental and functional similarities to neuronal cells. In addition, emerging applications of UCB derived AC133+ (CD133+) endothelial progenitor cells (EPCs) as imaging probe, regenerative agent, and gene delivery vehicle are mentioned that will further improve the understanding of use of UCB cells in therapeutic modalities. However, safe and effective protocols for cell transplantations are still required for therapeutic efficacy.

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“…To increase the level of functionally active enzymes in LSD patients, umbilical cord blood cell transplantation (UCBCT) is used. The therapeutic effect is achieved as the umbilical cord blood is a source of stem cells, which constantly express normal enzymes [16][17][18]. In the case of LSDs affecting the nervous system, UCBCT is also relevant, since it is known that blood-isolated immune cells are able to overcome the blood-brain barrier and deliver a normal enzyme to the nervous system [19,20].…”

Section: Introductionmentioning

confidence: 99%

Serum Cytokine Profile, Beta-Hexosaminidase A Enzymatic Activity and GM2 Ganglioside Levels in the Plasma of a Tay-Sachs Disease Patient after Cord Blood Cell Transplantation and Curcumin Administration: A Case Report

Shaimardanova

Chulpanova

Solovyeva

et al. 2021

Life

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Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder that occurs due to a deficiency of a β hexosaminidase A (HexA) enzyme, resulting in the accumulation of GM2 gangliosides. In this work, we analyzed the effect of umbilical cord blood cell transplantation (UCBCT) and curcumin administration on the course of the disease in a patient with adult TSD. The patient’s serum cytokine profile was determined using multiplex analysis. The level of GM2 gangliosides in plasma was determined using mass spectrometry. The enzymatic activity of HexA in the plasma of the patient was assessed using a fluorescent substrate assay. The HexA α-subunit (HexA) concentration was determined using ELISA. It was shown that both UCBCT and curcumin administration led to a change in the patient’s cytokine profile. The UCBCT resulted in an increase in the concentration of HexA in the patient’s serum and in an improvement in the patient’s neurological status. However, neither UCBCT nor curcumin were able to alter HexA activity and the level of GM2 in patient’s plasma. The data obtained indicate that UCBCT and curcumin administration can alter the immunity of a patient with TSD, reduce the level of inflammatory cytokines and thereby improve the patient’s condition.

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Analysis of the Efficiency of Gene-Cell Therapy in Transgenic Mice with Amyotrophic Lateral Sclerosis Phenotype

Cited by 5 publications

References 13 publications

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

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

Application of Umbilical Cord Blood Derived Stem Cells in Diseases of the Nervous System

Serum Cytokine Profile, Beta-Hexosaminidase A Enzymatic Activity and GM2 Ganglioside Levels in the Plasma of a Tay-Sachs Disease Patient after Cord Blood Cell Transplantation and Curcumin Administration: A Case Report

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