Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature.

Despite in vivo malignancy, ependymoma lacks cell culture models, thus limiting therapy development. Here, we used a tunable three-dimensional (3D) culture system to approximate the ependymoma microenvironment for recapitulating a patient's tumor in vitro. Our data showed that the inclusion of VEGF in serum-free, mixed neural and endothelial cell culture media supported the in vitro growth of all four ependymoma patient samples. The growth was driven by Nestin and Ki67 double-positive cells in a putative cancer stem cell niche, which was manifested as rosette-looking clusters in 2D and spheroids in 3D. The effects of extracellular matrix (ECM) such as collagen or Matrigel superseded that of the media conditions, with Matrigel resulting in the greater enrichment of Nestin-positive cells. When mixed with endothelial cells, the 3D co-culture models developed capillary networks resembling the in vivo ependymoma vasculature. The transcriptomic analysis of two patient cases demonstrated the separation of in vitro cultures by individual patients, with one patient's culture samples closely clustered with the primary tumor tissue. While VEGF was found to be necessary for preserving the transcriptomic features of in vitro cultures, the presence of endothelial cells shifted the gene's expression patterns, especially genes associated with ECM remodeling. The homeobox genes were mostly affected in the 3D in vitro models compared to the primary tumor tissue and between different 3D formats. These findings provide a basis for understanding the ependymoma microenvironment and enabling the further development of patient-derived in vitro ependymoma models for personalized medicine.

Human affection exchange: VI. Further tests of reproductive probability as a predictor of men's affection with their adult sons.

The authors examined the communication of affection in men's relationships with their fathers. Drawing from Affection Exchange Theory, the authors advanced four predictions: (a) heterosexual men receive more affection from their own fathers than do homosexual or bisexual men, (b) fathers communicate affection to their sons more through supportive activities than through direct verbal statements or nonverbal gestures, (c) affectionate communication between fathers and sons is linearly related to closeness and interpersonal involvement between them, and (d) fathers' awareness of their sons' sexual orientation is associated with the amount of affection that the fathers communicate to them. Participants were 170 adult men who completed questionnaires regarding affectionate communication in their relationships with their fathers. Half of the men were self-identified as exclusively heterosexual, and the other half were self-identified as exclusively homosexual or bisexual. The results supported all predictions substantially.