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Stem Cell Therapy for Multiple Sclerosis

  • Bilgesu Genc
  • Hemdem Rodi Bozan
  • Sermin Genc
  • Kursad GencEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1084)

Abstract

Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS). It is characterized by demyelination and neuronal loss that is induced by attack of autoreactive T cells to the myelin sheath and endogenous remyelination failure, eventually leading to functional neurological disability. Although recent evidence suggests that MS relapses are induced by environmental and exogenous triggers such as viral infections in a genetic background, its very complex pathogenesis is not completely understood. Therefore, the efficiency of current immunosuppression-based therapies of MS is too low, and emerging disease-modifying immunomodulatory agents such as fingolimod and dimethyl fumarate cannot stop progressive neurodegenerative process. Thus, the cell replacement therapy approach that aims to overcome neuronal cell loss and remyelination failure and to increase endogenous myelin repair capacity is considered as an alternative treatment option. A wide variety of preclinical studies, using experimental autoimmune encephalomyelitis model of MS, have recently shown that grafted cells with different origins including mesenchymal stem cells (MSCs), neural precursor and stem cells, and induced-pluripotent stem cells have the ability to repair CNS lesions and to recover functional neurological deficits. The results of ongoing autologous hematopoietic stem cell therapy studies, with the advantage of peripheral administration to the patients, have suggested that cell replacement therapy is also a feasible option for immunomodulatory treatment of MS. In this chapter, we overview cell sources and applications of the stem cell therapy for treatment of MS. We also discuss challenges including those associated with administration route, immune responses to grafted cells, integration of these cells to existing neural circuits, and risk of tumor growth. Finally, future prospects of stem cell therapy for MS are addressed.

Keywords

Experimental autoimmune encephalomyelitis Hematopoietic stem cell Induced pluripotent stem cell Mesenchymal stem cell Multiple sclerosis Neural stem cell Reprogramming Stem cell therapy 

Abbreviations

AD-MSCs

Adipose tissue-derived MSCs

AHSCT

Autologous hematopoietic stem cell transplantation

APC

Antigen-presenting cells

ASC

Adult stem cells

BBB

Blood–brain barrier

CNS

Central nervous system

Cy

Cyclophosphamide

DC

Dendritic cells

DMDs

Disease-modifying drugs

Dpi

Days of post immunization

EAE

Experimental autoimmune encephalomyelitis

EDSS

Expanded Disability Status Scale

ESC

Embryonic stem cells

G-CSF

Granulocyte colony-stimulating factor

GWAS

Genome-wide association studies

HLA

Human leukocyte antigen

HSC

Hematopoietic stem cell

HSCT

Hematopoietic stem cell transplantation

IDO

Indoleamine 2,3-dioxygenase

IFNɣ

Interferon gamma

IL-10

Interleukin-10

IL-1β

Interleukin-1beta

iNSC

Induced neural stem cell

iOL

Induced oligodendrocyte

iOPC

Induced oligodendrocyte progenitor cell

iPSC

Induced pluripotent stem cell

MBP

Myelin basic protein

MHC

Major histocompatibility complex

MOG

Myelin oligodendrocyte glycoprotein

MRI

Magnetic resonance imaging

MS

Multiple sclerosis

MSC

Mesenchymal stem cell

NK

Natural killer

NPC

Neural progenitor cells

NSC

Neural stem cell

OPC

Oligodendrocyte progenitor cell

PBMC

Peripheral blood mononuclear cells

PMS

Progressive MS

RRMS

Relapsing-remitting multiple sclerosis

SCT

Stem cell transplantation

SNP

Single nucleotide polymorphism

SPMS

Secondary progressive multiple sclerosis

SVZ

Subventricular zone

Th

T helper

TNF

Tumor necrosis factor

Tregs

T cell regulatory

TRM

Transplantation related mortality

Notes

Acknowledgment

Author thanks Assistant Prof. Dr. Yavuz Oktay for critical reading and editing of this chapter.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Bilgesu Genc
    • 1
  • Hemdem Rodi Bozan
    • 2
  • Sermin Genc
    • 3
    • 4
  • Kursad Genc
    • 4
    Email author
  1. 1.Department of Molecular Biology and GeneticsIzmir Institute of TechnologyIzmirTurkey
  2. 2.School of MedicineDokuz Eylul University Health CampusIzmirTurkey
  3. 3.Izmir Biomedicine and Genome CenterDokuz Eylul University Health CampusIzmirTurkey
  4. 4.Department of NeuroscienceInstitute of Health Sciences, Dokuz Eylul University Health CampusIzmirTurkey

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