Human Meningeal Cells (HMC)

Presence of Meningeal Cells Significantly Enhanced the Morphology and Phenotype of Cortical Organoids

Current human cortical organoid (hCO) models lack essential non-neural elements, such as meningeal layers required for physiologically-relevant corticogenesis, precluding proper modeling of brain development or neurodevelopmental disorders (NDDs). Here, Jailian et al. sought to create a new 3D co-culture system of hCO with meningeal cells isolated from early developmental stages.

Using an optimized co-culture system with addition of 8,000 meningeal cells to each single rosette at day 9 in vitro, they found that meningeal cells attached within 24h and enwrapped rosettes (Fig.1b1) giving rise to hCOMs with a significantly improved spherical morphology compared to controls (Fig. 1b2 and d). In real time, hCOMs also released less debris (Fig. 1b2 red arrows) and 1.5-fold more expansion compared to controls over 21 days (Fig. 1c), a result validated across 3 cell lines (CC1, PCDH19 and CHD2). Collectively, these findings demonstrate that our novel co-culture system from human iPSCs and meningeal cells together can efficiently improve the morphology and phenotype of cortical organoids and increase their growth in a defined time course.

CD99 Antibody Disrupts Leukemia-Meningeal Cell Adhesion

Despite high cure rates for acute lymphoblastic leukemia (ALL), CNS relapse remains a major therapeutic challenge due to chemoresistance mediated by leukemia-meningeal cell adhesion. Previous studies identified CD99 as a potential regulator of these interactions. Ebadi et al. investigated how CD99 antibody disrupts leukemia-meningeal adhesion and reverses chemoresistance, providing a novel therapeutic strategy for CNS relapse.

To assess CD99 antibody's impact on leukemia-meningeal adhesion, Jurkat/CEM T-ALL cells and primary T-ALL cells were co-cultured with human meningeal cells ± CD99 antibody (clone 0662). After 24h, flow cytometry with counting beads was performed to enumerate non-adherent leukemia cells after antibody treatment. The number of non-adherent leukemia cells was significantly increased with antibody treatment indicating disruption of adhesion (Fig. 2a). Pre-treatment of either cell type with antibody similarly led to an impairment of leukemia-meningeal adhesion. Dose response experiments indicated that the number of non-adherent cells was directly proportional to antibody concentration (Fig. 2b).