Mohammad Hassan Omrani
1 
, Sina Khodakarimi
1 , Hanieh Beyrampour-Basmenj
2 , Mahnaz Talebi
3 , Naeimeh Akbari-Gharalari
4,1 , Abbas Karimi
5 , Zeynab Aliyari-Serej
6 , Maryam Eyvazi
7 , Ahmad Mehdipour
8 , Abbas Ebrahimi-Kalan
1,3* 1 Department of Neurosciences and Cognition, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Medical Biotechnology, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
3 Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4 Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
5 Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
6 Department of Applied Cell Sciences, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
7 Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
8 Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract
Introduction: Multiple sclerosis (MS) is a complex immune-mediated disorder of the central nervous system (CNS) characterized by inflammation and degeneration, currently lacking a cure. The blood-brain barrier (BBB) challenges of delivery of therapeutic agents to affected neural tissues. Exosomes, with low-immunogenicity and the ability to cross biological barriers, offer a promising avenue for targeted delivery of neurotrophic factors (NTFs) to support neuronal survival and regeneration. This study investigated the therapeutic potential of stem cell-derived exosomes (SCDEs) and Cerebrolysin-loaded exosomes (CLE) in an experimental autoimmune encephalomyelitis (EAE) model, a preclinical paradigm for MS.
Objectives: The co-delivery of NTFs and exosomes aimed to modulate the immune response and promote remyelination and neuroprotection in EAE.
Materials and Methods: An EAE modeling was induced in C57BL/6 mice in an experimental study, treated with SCDE, CBL, or CLE by intraperitoneal administration. Assessments included clinical scoring, gene expression analysis in splenocytes, and cytokine quantification.
Results: Results showed that the CLE group exhibited significant improvement in behavioral manifestations compared to SCDE and CBL groups. CLE treatment stimulated survival signaling pathways, influencing EAE progression, and suppressed pro-inflammatory transcription factors while upregulating anti-inflammatory factors in splenocytes. CLE significantly reduced pro-inflammatory cytokine interferon-gamma (IFN‐γ) in serum samples, suggesting a neuroprotective effect by targeting pathways and overcoming BBB limitations.
Conclusion: The observed immune modulation and neural protection in the CLE group suggest its potential for MS treatment. Further investigations are needed to elucidate mechanisms and explore clinical applications. The study highlights the promise of CLE-based therapy in addressing MS pathology.