Akinola S. Surgical correction of demyelinating injuries of the central nervous system using mesenchymal stem cells (experimental study)

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0419U001583

Applicant for

Specialization

  • 14.01.05 - Нейрохірургія

15-10-2019

Specialized Academic Board

Д 26.557.01

The State institution "Romodanov neurosurgery institute, National academy of medical sciences of Ukraine"

Essay

The dissertation presents a new approach to solving the scientific problem - improvement of the results of treatment of demyelinating injuries of the central nervous system under conditions of experimental modeling by xenotransplantation of mesenchymal stem cells (MSCs) of umbilical cord blood counts and anti - inflammatory interleukin - 10 (IL - 10). The study was performed on white, non-breeding rats, females of 3 months of age, weighing 230 ± 20 g (n = 104, 6 groups). Experimental allergic encephalomyelitis (EAE) was used as a demyelinating lesion model, which was obtained by immunizing animals with a Freund full adjuvant (2 mg/ml Mycobacterium tuberculosis). Optimization of the EAE model allowed to obtain a chronic relapsing course of the disease. The course of the disease (a 5-point scale for assessing the clinical condition of animals), behavioral reactions (open field test), cultures, molecular-genetic, morphological and statistical studies were studied. It is confirmed that the morphology of MSCs and the expression of their surface markers are preserved during 2 cultivation passages. At a later date there are signs of degradation of culture and loss of cells of the mesenchymal multipotent phenotype. The PCR method has shown that when introduced into the subarachnoidal CSF of animals from the EAE MSC umbilical cord retain their viability for at least 8 days and are capable of humming. Introduction to the liver of animals MSC and anti-inflammatory IL-10 in various combinations promotes a complete clinical regression of symptoms and recovery of animals up to 32 days of the experiment. The study of structural signs of de-remyelination at the ultrastructural level shows that MSCs have a positive effect already in the early stages of the study (35 days), contributing to the activation of the process of remyelination of axons. However, the complete normalization of the ultrastructural organization of myelinated axons and cellular elements of the spinal cord does not occur. Established survival of xenogeneous MSCs, tropism and their migration ability to the focal point of the central nervous system, positive effects on the course of EAE can be widely used in practical medicine. Neurosurgical methods (introduction into a large occipital cistern, ventricles of the brain, etc.) extend the possibilities of using MSCs and their synthesized products (cytokines) that do not penetrate the blood-brain barrier.

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