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Gene-cell therapy for Alzheimer disease
Russia (TaMSA-Tatarstan) - Kazan State Medical University, Kazan
Professor Zefirov Andrey Lvovich, MD, PhD, DSc
Mukhamedyarov Marat Aleksandrovich, MD, PhD, Associate professor of Dept. Physiology
Type of Research Project
- Basic science
What is the background of the project?
Gene-cell therapy - treatment of disease by injecting of genetically modified cells. Within this project the cord blood mononuclear cells with overexpression of growth and trophic factors, such as GDNF and VEGF, will used for activation of neurogenesis in the hippocampus of mice with a model of Alzheimer's disease. Neurogenesis will be assessed by the character and intensity of the expression of markers of neural stem and progenitor cells - nestin and doublecortin.
What is the aim of the project?
lzheimer’s disease is a progressive incurable neurodegenerative disease manifested by dementia and other cognitivedisorders. Gene-cell therapy is one of the most promising trends in the development of treatment for Alzheimer’s disease.The study was aimed to evaluate the therapeutic potential of intravenous transplantation of human umbilical cord bloodmononuclear cells (UCBMCs) transduced with adenoviral vectors overexpressing nerve growth factor (NGF) for thetreatment of Alzheimer’s disease in an APP/PS1 transgenic mice model. The transplantation of NGF-expressingUCBMCs was found to improve spatial memory and decrease anxiety in APP/PS1 mice. Grafted cells and their expressionof NGF were detected in the cortex and hippocampus of transgenic mice in the period up to 90 days after transplantation.Thus, gene-cell therapy based on the use of NGF-overexpressing UCBMCs is a promising approach for the developmentof Alzheimer’s disease treatments.
What techniques and methods are used?
Cell Preparation and In Vitro Analysis Umbilical cord blood was taken after obtaining informed con-sent of the pregnant and prenatal screening for contraindica-tions to blood donation. Blood was collected in CPDA-1250GG plastic containers (Terumo, Japan) and delivered to labo-ratory. Western Blot Analysis of Genetically ModifiedUCBMCs Expression of egfp and ngf genes intransduced UCBMCs was assessed by Western blot and fluorescent microscopy. Behavioral Tests: T-maze T-maze setup (Open Science, Russia) was used tostudy spatial memory in mice. Plus Maze Plus-maze setup (Open Science, Russia) was usedto study orientation, exploratory behavior, and anxiety inmice. Open field Locomotor activity in mice was evaluated using anopen-field setup (Open Science, Russia).
What is the role of the student?
What are the tasks expected to be accomplished by the student?
The student will take active part in the practical aspect of the project. During the laboratory work the student will be taught basic techniques of the method of Cell Preparation and In Vitro Analysis, Western Blot Analysis of Genetically ModifiedUCBMCs All methods will be performed under supervision after clear and detailed explanation. Also, student will be highly involved in the analysis of the final results.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Basic knowledges in biomedicine
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months)
- Rizvanov; A.A.; et al.; Genetically modified human umbilical cord blood cells expressing vascular endothelial growth factor and fibroblast growth factor 2 differentiate into glial cells after transplantation into amyotrophic lateral sclerosis transgenic mice. Exp Biol Med (Maywood); 2011. 236(1): p. 91-8. 2. Rocha; N.P.; et al.; Peripheral blood mono-nuclear cells derived from Alzheimer's disease patients show elevated baseline levels of secreted cytokines but resist stimulation with beta-amyloid peptide. Mol Cell Neurosci; 2012. 49(1): p. 77-84. 3. Mukhamedyarov; M.A.; et al.; Analysis of the efficiency of gene-cell therapy in transgenic mice with amyotrophic lateral sclerosis phenotype. Bull Exp Biol Med; 2013. 154(4): p. 558-61. 4. Islamov; R.R.; et al.; 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. Curr Gene Ther; 2015. 15(3): p. 266-76. 5. Bachstetter; A.D.; et al.; Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain. BMC Neurosci; 2008. 9: p.22. 6. Zhao; C.; W. Deng; and F.H. Gage; Mechanisms and functional implications of adult neurogenesis. Cell; 2008. 132(4): p. 645-60.
- 2. Rocha; N.P.; et al.; Peripheral blood mono-nuclear cells derived from Alzheimer's disease patients show elevated baseline levels of secreted cytokines but resist stimulation with beta-amyloid peptide. Mol Cell Neurosci; 2012. 49(1): p. 77-84.
- 3. Mukhamedyarov; M.A.; et al.; Analysis of the efficiency of gene-cell therapy in transgenic mice with amyotrophic lateral sclerosis phenotype. Bull Exp Biol Med; 2013. 154(4): p. 558-61.
- 4. Islamov; R.R.; et al.; 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. Curr Gene Ther; 2015. 15(3): p. 266-76.
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