Stem Cell Therapies for Progressive Multiple Sclerosis.

Jayden A Smith,Luca Peruzzotti-Jametti,Stefano Pluchino,Alexandra M Nicaise,Rosana-Bristena Ionescu,Regan Hamel

doi:10.3389/fcell.2021.696434

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and axonal degeneration. MS patients typically present with a relapsing-remitting (RR) disease course, manifesting as sporadic attacks of neurological symptoms including ataxia, fatigue, and sensory impairment. While there are several effective disease-modifying therapies able to address the inflammatory relapses associated with RRMS, most patients will inevitably advance to a progressive disease course marked by a gradual and irreversible accrual of disabilities. Therapeutic intervention in progressive MS (PMS) suffers from a lack of well-characterized biological targets and, hence, a dearth of successful drugs. The few medications approved for the treatment of PMS are typically limited in their efficacy to active forms of the disease, have little impact on slowing degeneration, and fail to promote repair. In looking to address these unmet needs, the multifactorial therapeutic benefits of stem cell therapies are particularly compelling. Ostensibly providing neurotrophic support, immunomodulation and cell replacement, stem cell transplantation holds substantial promise in combatting the complex pathology of chronic neuroinflammation. Herein, we explore the current state of preclinical and clinical evidence supporting the use of stem cells in treating PMS and we discuss prospective hurdles impeding their translation into revolutionary regenerative medicines.

Highlights

Multiple sclerosis (MS) is a chronic neuroinflammatory condition that affects over 2 million people worldwide (Stenager, 2019)
While advances in the development of immunomodulatory diseasemodifying therapies (DMTs) have had a substantial impact on the severity and frequency of relapses (Derfuss et al, 2020), within 30 years of diagnosis, two-thirds of RRMS patients will transition into the debilitating secondary progressive (SP) phase of the disease (Scalfari et al, 2014)
There are no proven interventions able to halt the gradual accumulation of disability associated with progressive MS (PMS), let alone effectively promote repair of the damaged central nervous system (CNS)

Summary

INTRODUCTION

Multiple sclerosis (MS) is a chronic neuroinflammatory condition that affects over 2 million people worldwide (Stenager, 2019). Both brain atrophy and the number of transected axons correlate with the degree of inflammation in PMS lesions, suggesting a link between immune cell activation and neuronal damage (Frischer et al, 2009) In this sense, ROS and RNS generated from both subsets of MPs may be the key drivers affecting mitochondrial functionality in neurons, leading to a highly destructive environment permissive to continued neuronal death. Despite findings suggesting nHSCs as promising therapeutic tools for diseases such as PMS in which tissue repair is needed and/or inflammation is extensive, clinical translation of nHSC transplantation has met some barriers These include limited engraftment duration, little in vivo differentiation, and restricted accessibility into damaged sites (Yousefi et al, 2019). MOG-induced chronic-EAE in WT female mice TMEV-induced demyelination in WT female mice

Key Findings

Findings

CONCLUSION