Hyaluronic Acid Prevents Fusion of Brain Tumor-Derived Spheroids and Selectively Alters Their Gene Expression Profile.

Hyaluronic acid (HA), a major glycosaminoglycan of the brain extracellular matrix, modulates cell behaviors through binding its receptor, Cd44. In this study, we assessed the influence of HA on high-grade brain tumors in vitro. The model comprised cell cultures derived from six rodent carcinogen-induced brain tumors, forming 3D spheroids prone to spontaneous fusion. Supplementation of the standard culture medium with 0.25% HA significantly inhibited the fusion rates, preserving the shape and size uniformity of spheroids. The 3D cultures were assigned to two groups; a Cd44lo group had a tenfold decreased relative expression of Cd44 than another (Cd44hi) group. In addition, these two groups differed by expression levels of Sox2 transcription factor; the correlation analysis revealed a tight negative association for Cd44 and Sox2. Transcriptomic responses of spheroids to HA exposure also depended on Cd44 expression levels, from subtle in Cd44lo to more pronounced and specific in Cd44hi, involving cell cycle progression, PI3K/AKT/mTOR pathway activation, and multidrug resistance genes. The potential HA-induced increase in brain tumor 3D models' resistance to anticancer drug therapy should be taken into account when designing preclinical studies using HA scaffold-based models. The property of HA to prevent the fusion of brain-derived spheroids can be employed in CNS regenerative medicine and experimental oncology to ensure the production of uniform, controllably fusing neurospheres when creating more accurate in vitro brain models.

Optical coefficients as tools for increasing the optical coherence tomography contrast for normal brain visualization and glioblastoma detection.

The methods used for digital processing of optical coherence tomography (OCT) and crosspolarization (CP) OCT images are focused on improving the contrast ratio of native structural OCT images. Such advances are particularly important for the intraoperative detection of glioma margins where the visual assessment of OCT images can be difficult and lead to errors. The aim of the study was to investigate the application of optical coefficients obtained from CP OCT data for the differentiation of glial tumorous tissue from a normal brain. Pseudocolor en-face OCT maps based on two optical coefficients (the commonly used rate of attenuation in the cochannel, and in addition, the interchannel attenuation difference) were constructed for normal rat brain coronal cross sections and for brains with a 101.8 rat glioblastoma model. It was shown that the use of optical coefficients significantly increased the available information from the OCT data in comparison with unprocessed images. As a result, this allowed contrasting of the white matter from the gray matter and tumorous tissue ex vivo, and for this purpose, the interchannel attenuation difference worked better. The interchannel attenuation difference values of white matter were at least seven and two times higher than corresponding values of the cortex and tumorous tissue, whereas the same parameter for cochannel attenuation coefficient values of white matter are about 4 and 1.4. However, quantitative analysis shows that both coefficients are suitable for the purpose of glioblastoma detection from normal brain tissue regardless of whether a necrotic component was present (in all compared groups p < 0.001 ).