Migration of normal stem CD34 + cells to the brain in experimental models of ischemic stroke and glioblastoma

Abstract

Background: Glyoblastoma is one of the most common brain tumors, which is characterized by high aggressiveness and unfavorable prognosis. One of the leading causes of the therapeutic resistance of glioblastoma is associated with tumor stem cells (TSC). One of the promising ways to solve this problem is the creation of biomedical products based on stem and progenitor cells of the human bone marrow. We have established, in vitro, that the stem CD34 + cells of the bone marrow are able to migrate toward the cells of different types. In vivo, stem cells of bone marrow CD 34+ actively migrate to the tumor tissue, where they accumulate in the area of invasion and penetrate into the hypoxic zones of the tumor. We suggested that the appearance of CD34 + cells in the neoplastic tissue is associated with the processes of neoplastic angiogenesis, and the role of hypoxia in this case is secondary. The study of migration processes and the homing of stem cells in the pathological focus in the brain on experimental models of acute ischemia and glioblastoma. Methods: The work was performed on 60 mature Wistar female rats divided into 2 groups (N = 30). The animals of the first group underwent stereotactic implantation of C6 glioma cells in the brain, tumor development was confirmed by magnetic resonance imaging (MRI) data; the second group - the ligation of the common and internal carotid artery on the left was performed surgically. The development of the stroke was confirmed by MRI data. The haploidentical CD34 + stem cells stained with the fluorescent vital dye Vybrant® CFDA SE (V12883, Molecular Probes, USA) were injected into the tail vein. The animals were removed from the experiment on days 4 and 8, the material was subjected to morphological and immunohistochemical analysis. Results: Four days after the infusion of cells on the glioblastoma model, the fluorescent label was detected at the periphery of the tumor site, which was associated with localized blood vessels in this region. On day 8, the area of fluorescing objects was 12.7 ± 9.2% at the tumor boundary, 47.6 ± 9.3% in the parenchyma of the tumor tissue. In the experimental model of ischemia, fluorescent substances in the spectrum of characteristic CFDA on days 4 and 8 were not detected. Conclusions: Hypoxic brain damage is not enough to ensure the effective homing of cells in the tumor. With a glioblastome formed a specific type of microglia, this circumstance allows one to assume the possibility of increasing the life expectancy of patients with glioblastoma. Legal entity responsible for the study: School of Biomedicine, Far Eastern Federal University, Russian Federation Funding: Russian Scientific Fund (14-15-00084) Disclosure: All authors have declared no conflicts of interest.