Exploring the role of perivascular cells on fibrosis in EAE upon C-MANF treatment
Year: 2025
Type: article
Abstract: Multiple sclerosis (MS) is an autoimmune disease characterized by demyelinated lesions in the central nervous system (CNS). While the CNS has remyelinating mechanisms, these often fail in MS, leading to chronical disease and disability. One of the biggest challenges in MS tissue regeneration is fibrosis, a physical barrier that prevents remyelinating oligodendrocytes from entering the lesion. Fibrotic scarring in the CNS is driven by perivascular and meningeal fibroblasts (FBs) that detach from the vessels and infiltrate the lesions. While there are no approved treatments for MS that target fibrosis, the C-terminal fragment of the mesencephalic astrocyte derived neurotrophic factor (MANF) is able to reduce fibrosis-related genes such as Col1a1 in an ex-vivo model of demyelination. Here, we investigate the identity of perivascular cells (PVCs) and meningeal fibroblasts (MFBs) in vitro and the role they have in fibrosis in experimental autoimmune encephalomyelitis (EAE), as well as assess the effect that subcutaneous (s.c.) C-MANF treatment has on them and on fibrosis in the lesions. We show that the PVCs are indeed of perivascular origin through the expression of CNS-resident PVCs/MFBs marker PDGFrβ and also consistently express markers of meningeal and perivascular FBs. Additionally, they express fibronectin, alluding to their fibrotic potential. In EAE spinal cord (SC), we show an increase in fibrosis and PVCs-related markers, but no beneficial effect against fibrosis or removal of infiltrating cells after C-MANF treatment. While these findings are unexpected, they propose new avenues to explore in tissue regeneration research.
Source: Työväentutkimus Vuosikirja
Author: Medina Leskinen, Saila Maria
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7199629281