Porcu, L. | Search bioRxiv

bioRxiv2025

Imaging progenitor cell differentiation during central nervous system remyelination using an MRI gene reporter

Demyelination, the loss of the myelin sheath from around otherwise intact axons, occurs in several diseases, most notably multiple sclerosis (MS). Demyelinated axons that are not remyelinated are vulnerable to irreversible degeneration and therefore therapies that enhance remyelination have been sought. However, there remains a paucity of suitable outcome measures to assess their efficacy. Magnetic Resonance Imaging (MRI) is a non-invasive imaging modality that is used both preclinically and clinically for the assessment of anatomy and tissue function. Here we describe an MRI technique for following the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes during the spontaneous regenerative process of remyelination in vivo. OPCs were transduced in situ with a lentiviral vector expressing an organic anion transporting polypeptide (Oatp1a1) under the control of the differentiation-specific Myelin Basic Protein (MBP) promoter. Oatp1a1 mediates cell uptake of a gadolinium-based MRI contrast agent (Primovist), allowing detection of the cells in T1-weighted MR images. Uptake of the contrast agent is restricted to MBP-expressing cells, which is most highly expressed during myelin sheath formation, thereby allowing progenitor-mediated, and potentially oligodendrocyte-mediated, remyelination to be monitored non-invasively in vivo using MRI. These findings provide the foundation for the development of direct methods for assessing the efficacy of pro-remyelination therapies.

neuroscience↗

bioRxiv2025

Unravelling the in vivo traits of vasculogenic mimicry

Vasculogenic mimicry (VM) describes the ability of cancer cells to acquire endothelial properties and form vessel-like channels that facilitate tumour blood supply. While the molecular drivers of VM have been well-explored in cell cultures and biopsies, an in vivo description remains elusive. Here, we used graph theory to define VM biomarkers and elucidate the spatiotemporal dynamics of VM using in vitro and in vivo breast cancer models with and without anti-angiogenic treatment. Optical microscopy was used to assess pseudo-vascular networks in vitro while photoacoustic imaging across scales was applied in vivo to identify and locate haemoglobin contrast-derived blood vessel morphology and functionality. VM was associated with greater oxygenation heterogeneity and poorer anti-angiogenic response, reflected as stable meshed networks in vitro and blood-containing circular structures in vivo. We demonstrate for the first time a multi-scale approach bridging the in vitro-in vivo translational gap to assess anti-vascular treatment resistance and the therapeutic potential in vasculogenic mimicry-rich tumours, exploring novel avenues in preclinical drug screening and systemic drug delivery.

cancer biology↗