A review on stem cell therapy for multiple sclerosis: special focus on human embryonic stem cells

Stem Cells and Cloning: Advances and Applications Dovepress open access to scientific and medical research Review Stem Cells and Cloning: Advances and Applications downloaded from https://www.dovepress.com/ by 51.254.16.214 on 13-Jul-2018 For personal use only. Open Access Full Text Article A review on stem cell therapy for multiple sclerosis: special focus on human embryonic stem cells This article was published in the following Dove Press journal: Stem Cells and Cloning: Advances and Applications Geeta Shroff Department of Stem Cell Therapy, Nutech Mediworld, New Delhi, India Introduction Correspondence: Geeta Shroff Nutech Mediworld, H-8, Green Park Extension, New Delhi 110016, India Tel +91 11 26180039 Fax +91 11 26560089 Email Promising advances have been made in the recent years in stem cell transplantation to treat and cure damaged tissues, injuries, and various diseases. This is especially true with the various autoimmune disorders, specifically for the ones which are associated with nervous system, where damage often appears from the degeneration of cells.1 Treatment using cell therapy involves a form of immune suppression but unlike standard immune-based drugs, it is designed to reset rather than suppress the immune system. Scientists define three ways to use stem cell therapy: the first involves the use of stem cells to replace damaged myelin-forming oligodendrocytes within the central nervous system (CNS);2,3 the second aims to replace the individual’s malfunctioning immune system, making use of hematopoietic stem cells (HSCs);4,5 and the third seeks to utilize the endogenous stem cell populations by mobilization with or without in vitro expansion, exploiting their reparative and neuroprotective properties.6,7 Studies have been carried out for various type of stem cells: autologous hematopoietic stem cells (AHSCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and human embryonic stem cells (hESCs).8 hESC transplantation is a controversial yet a powerful strategy for the treatment of patients with autoimmune diseases. hESC lines can differentiate into neural precursor cells and neurons, astrocytes, and oligodendrocytes that show their potential in treating several incurable neurological disorders like spinal cord injury,9,10 cerebral palsy,11 1 submit your manuscript | www.dovepress.com Stem Cells and Cloning: Advances and Applications 2018:11 1–11 Dovepress © 2018 Shroff. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/SCCAA.S135415 Powered by TCPDF (www.tcpdf.org) Abstract: Multiple sclerosis (MS), a complex disorder of the central nervous system (CNS), is characterized with axonal loss underlying long-term progressive disability. Currently available therapies for its management are able to slow down the progression but fail to treat it completely. Moreover, these therapies are associated with major CNS and cardiovascular adverse events, and prolonged use of these treatments may cause life-threatening diseases. Recent research has shown that cellular therapies hold a potential for CNS repair and may be able to provide protection from inflammatory damage caused after injury. Human embryonic stem cell (hESC) transplantation is one of the promising cell therapies; hESCs play an important role in remyelination and help in preventing demylenation of the axons. In this study, an overview of the current knowledge about the unique properties of hESC and their comparison with other cell therapies has been presented for the treatment of patients with MS. Keywords: multiple sclerosis, stem cells, human embryonic stem cells, remyelination, axonal loss, neurological disorder Dovepress Stem Cells and Cloning: Advances and Applications downloaded from https://www.dovepress.com/ by 51.254.16.214 on 13-Jul-2018 For personal use only. Shroff multiple sclerosis (MS),12 Parkinson’s disease,13 and many more. The remarkable properties of hESC therapy in treating various terminal conditions both in vitro and in vivo could be used as the first-line therapy in the future.14 Of the various neurological diseases, MS is one of the most complicated in which the underlying pathological mechanism remains unclear, and the incompetence of a large number of promising treatments for the disease makes it an ideal target for use in regenerative medicine.15 Pluripotency, self-renewal, and ability to regenerate and differentiate into neuronal cells are the promising factors to use hESCs in treating MS. These properties make them an ideal resource of unlimited supply of neural derivatives.16,17 This review provides an account on the role of hESC lines in treating MS and their comparison with other cellular therapies. Subsequently, this will discuss the development of hESC line at the Department of Stem Cell Therapy, Nutech Mediworld, India that has been able to treat various terminal diseases. MS and its pathogenesis MS is a chronic inflammatory demyelinating disease of the CNS which involves the loss of myelin-forming oligodendrocytes that can be followed by a spontaneous and an efficient regenerative process called remyelination.18 It affects the people of almost all the ages in many parts of the world, mostly young people, especially more prevalent in women, and among those in northern latitudes. Relapsing–remitting multiple sclerosis (RRMS) is the most common form of MS. The disease course is biphasic; initially, there are alternating episodes of acute neurological deficits or worsening episodes of relapses followed by a complete or partial recovery (i.e., remission). Within a span of 15–20 years, most (70%) of the patients with RRMS develop secondary progressive MS which is characterized by a progressive neurological decline independent of relapses (inflammation).19 MS has a genetic susceptibility, but it is not directly inherited.20 The disease has an unknown etiology with no cure; only symptomatic treatment is available.21,22 Current treatment approach for MS and their limitations Since 2010, various oral therapies were approved which offer added convenience, but all these therapies provided only symptomatic relief.22,23 The currently available treatments mainly target the underlying immunologic etiology of MS. Most of the therapies are composed of medications that are either immunomodulatory or immunosuppressive and a (...truncated)