CNS Disease Diminishes the Therapeutic Functionality of Mesenchymal Stem Cells

CNS Disease Diminishes the Therapeutic Functionality of Mesenchymal Stem Cells

Bibliographic Details
Main Author: Sargent, Alex
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2018
Subjects:
Neurosciences
mesenchymal stem cells
multiple sclerosis
experimental autoimmune encephalomyelitis
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1510913988194956
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case15109139881949562021-08-03T07:04:34Z CNS Disease Diminishes the Therapeutic Functionality of Mesenchymal Stem Cells Sargent, Alex Neurosciences mesenchymal stem cells multiple sclerosis experimental autoimmune encephalomyelitis Mesenchymal stem cells (MSCs) have recently emerged as a potentially powerful cellular therapy for both inflammatory and neurological diseases such as multiple sclerosis (MS). Studies in animal models of MS, particularly experimental autoimmune encephalomyelitis (EAE), have demonstrated a remarkable ability of systemically delivered MSCs to suppress inflammation and improve neurological and functional recovery. Based on these preclinical studies, over twenty clinical trials have been initiated to evaluate the potential of MSCs to treat MS. Most of these trials use autologous MSCs (from the MS patients), in contrast to previous work done in the EAE model that used MSCs from healthy animals or donors. This raises a serious and unresolved issue about whether autologous MSCs are equivalent to healthy MSCs in their potential to treat diseases like MS. To determine if and how inflammatory diseases like MS affect MSC functionality, we cultured MSCs from the bone marrow of MOG35-55 induced EAE mice at different phases of disease and compared them to naive MSCs derived from healthy donors in their therapeutic potential. We found that EAE-MSCs have less therapeutic efficacy compared to naive MSCs in their ability to ameliorate EAE. The lack of therapeutic efficacy in EAE-MSCs reflected changes in their secretion of paracrine inflammatory cytokines, which EAE-MSCs up regulate at both the protein and gene level. Co-culture studies showed that conditioned medium from EAE-MSCs has differential effects on immune cell activation and neural cell development compared to naive MSCs. Furthermore, we found that bone marrow MSCs derived from MS patients show similar changes to EAE-MSCs and also lack therapeutic efficacy in treating EAE. Collectively, our data shows that disease diminishes the therapeutic functionality of MSCs, raising concern about the continued use of autologous MSCs as a potential therapy for MS. 2018-02-02 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1510913988194956 http://rave.ohiolink.edu/etdc/view?acc_num=case1510913988194956 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Neurosciences
mesenchymal stem cells
multiple sclerosis
experimental autoimmune encephalomyelitis
spellingShingle Neurosciences
mesenchymal stem cells
multiple sclerosis
experimental autoimmune encephalomyelitis
Sargent, Alex
CNS Disease Diminishes the Therapeutic Functionality of Mesenchymal Stem Cells
author Sargent, Alex
author_facet Sargent, Alex
author_sort Sargent, Alex
title CNS Disease Diminishes the Therapeutic Functionality of Mesenchymal Stem Cells
title_short CNS Disease Diminishes the Therapeutic Functionality of Mesenchymal Stem Cells
title_full CNS Disease Diminishes the Therapeutic Functionality of Mesenchymal Stem Cells
title_fullStr CNS Disease Diminishes the Therapeutic Functionality of Mesenchymal Stem Cells
title_full_unstemmed CNS Disease Diminishes the Therapeutic Functionality of Mesenchymal Stem Cells
title_sort cns disease diminishes the therapeutic functionality of mesenchymal stem cells
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2018
url http://rave.ohiolink.edu/etdc/view?acc_num=case1510913988194956
work_keys_str_mv AT sargentalex cnsdiseasediminishesthetherapeuticfunctionalityofmesenchymalstemcells
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