Open AccessLumbar spine intrathecal transplantation of neural precursor cells promotes oligodendrocyte proliferation in hot spots of chronic demyelination
Author(s) -
Theotokis Paschalis,
Kesidou Evangelia,
Mitsiadou Dimitra,
Petratos Steven,
Damianidou Olympia,
Boziki Marina,
Chatzidimitriou Anastasia,
Grigoriadis Nikolaos
Publication year - 2022
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.13040
Subject(s) - experimental autoimmune encephalomyelitis , multiple sclerosis , oligodendrocyte , remyelination , transplantation , neuropathology , biology , precursor cell , spinal cord , medicine , immunology , central nervous system , pathology , cancer research , neuroscience , cell , myelin , disease , genetics
Experimental autoimmune encephalomyelitis (EAE) is a basic and reliable model used to study clinical and pathological hallmarks of multiple sclerosis (MS) in rodents. Several studies suggest neural precursor cells (NPCs) as a significant research tool while reporting that transplanted NPCs are a promising therapeutic approach to treating neurological disorders, such as MS. The main objective was to approach a preclinical, in vivo scenario of oligodendrogenesis with NPCs, targeting the main chronic demyelinated lumbosacral milieu of EAE, via the least invasive delivery method which is lumbar puncture. We utilized MOG 35‐55 peptide to induce EAE in C57BL/6 mice and prior to the acute relapse, we intervened with either the traceable GFP + cellular therapy or saline solution in the intrathecal space of their lumbar spine. A BrdU injection, which enabled us to monitor endogenous proliferation, marked the endpoint 50 days post‐induction (50 dpi). Neuropathology with high‐throughput, triple immunofluorescent, and transmission electron microscopy (TEM) data were extracted and analyzed. The experimental treatment attenuated the chronic phase of EAE (50 dpi; score <1) following an acute, clinical relapse. Myelination and axonal integrity were rescued in the NPC‐treated animals along with suppressed immune populations. The differentiation profile of the exogenous NPCs and endogenous BrdU + cells was location‐dependent where GFP + ‐rich areas drove undifferentiated phenotypes toward the oligodendrocyte lineage. In situ oligodendrocyte enrichment was demonstrated through increased ( p < 0.001) gap junction channels of Cx32 and Cx47, reliable markers for proliferative oligodendroglia syncytium. TEM morphometric analysis ultimately manifested an increased g‐ratio in lumbosacral fibers of the recovered animals ( p < 0.001). Herein, we suggest that a single, lumbar intrathecal administration of NPCs capacitated a viable cellular load and resulted in clinical and pathological amelioration, stimulating resident OPCs to overcome the remyelination failure in EAE demyelinating locale.