<mods:mods xmlns:mods="http://www.loc.gov/mods/v3" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" ID="etd1625" xsi:schemaLocation="http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd">
    <mods:titleInfo>
        <mods:title>The Effects of Aging and Chemotherapeutics on 

Mesenchymal Stem Cell Regenerative Properties </mods:title>
    </mods:titleInfo><mods:name type="personal">
        <mods:namePart>Beane, Olivia S</mods:namePart>
    <mods:role>
        <mods:roleTerm type="text">creator</mods:roleTerm>
    </mods:role>
    </mods:name>
<mods:originInfo>
    <mods:copyrightDate>2016</mods:copyrightDate>
</mods:originInfo>
<mods:physicalDescription>
        <mods:extent>xvii, 235 p.</mods:extent>
        <mods:digitalOrigin>born digital</mods:digitalOrigin>
</mods:physicalDescription>
<mods:note>Thesis (Ph.D. -- Brown University (2016)</mods:note>
<mods:name type="personal">
<mods:namePart>Darling, Eric</mods:namePart>
<mods:role>
<mods:roleTerm type="text">Director</mods:roleTerm>
</mods:role>
</mods:name>

<mods:name type="personal">
<mods:namePart>Ciombor, Deborah</mods:namePart>
<mods:role>
<mods:roleTerm type="text">Reader</mods:roleTerm>
</mods:role>
</mods:name>

<mods:name type="personal">
<mods:namePart>Hoffman-Kim, Diane</mods:namePart>
<mods:role>
<mods:roleTerm type="text">Reader</mods:roleTerm>
</mods:role>
</mods:name>

<mods:name type="personal">
<mods:namePart>Franck, Christian</mods:namePart>
<mods:role>
<mods:roleTerm type="text">Reader</mods:roleTerm>
</mods:role>
</mods:name>

<mods:name type="personal">
<mods:namePart>Darling, Louise</mods:namePart>
<mods:role>
<mods:roleTerm type="text">Reader</mods:roleTerm>
</mods:role>
</mods:name>
<mods:name type="corporate">
        <mods:namePart>Brown University. Biomedical Engineering</mods:namePart>
        <mods:role>
            <mods:roleTerm type="text">sponsor</mods:roleTerm>
        </mods:role>
        </mods:name>
    <mods:genre authority="aat">theses</mods:genre>
    <mods:abstract>The work in this thesis demonstrates that mesenchymal stem cell (MSC) function is

influenced by aging and chemotherapy. Furthermore, these results illustrate that inherent

differences exist among cell types.  Examining the effects of environmental factors on different

cell types and identifying mechanisms behind these responses is necessary to understand

consequential tissue damage and optimize regenerative therapies.  A literature review was

conducted to examine differences among isolation, characterization, and chondrogenic

differentiation procedures of various stem cell types. Techniques were predominantly stem cell-

specific and varied widely across literature, preventing accurate comparisons. Revealing inherent

differences among cell types and inconsistencies within the field are important to improve

cartilage repair strategies.  To understand how stem cell type influences sensitivity to adverse

aging effects, regenerative properties were compared between young and old cells derived from

muscle, bone marrow, and adipose tissue. MSCs were disparately affected by age. However,

total metabolite production was comparable among old cells, indicating that MSCs from all three

sources are potential candidates for regenerative therapies targeting older populations. The

effects of chemotherapy on adipose derived stem cell (ASC) properties were also examined and

compared with a normal human fibroblast (NHF) population. Treatment with several commonly

used drugs in vitro impaired ASC and NHF proliferation. However, ASCs were more resistant

than NHFs to methotrexate (MTX) and retained their multipotency after exposure. These results

suggest that ASCs are a potential source to treat drug-induced tissue loss. Investigation into the

mechanism behind normal cell response to MTX was conducted by overexpression and

knockdown of dihydrofolate reductase (DHFR), the target of the drug. Overexpression and

endogenous nucleoside delivery rescued normal cells from adverse effects, identifying DHFR as a resistance mechanism and potential target for MTX normal cell rescue therapies. When ASC

MTX response was compared to other stem and non-stem cell populations, it was observed that

undifferentiated MSCs were more resistant than differentiating and terminally differentiated cell

types, suggesting that stemness could play a role in MTX resistance, as well.</mods:abstract>

    <mods:subject xmlns:xlink="http://www.w3.org/1999/xlink" authority="FAST" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/1763304"><mods:topic>Mesenchymal stem cells</mods:topic></mods:subject><mods:subject xmlns:xlink="http://www.w3.org/1999/xlink" authority="FAST" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/800293"><mods:topic>Aging</mods:topic></mods:subject><mods:subject xmlns:xlink="http://www.w3.org/1999/xlink" authority="FAST" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/853595"><mods:topic>Chemotherapy</mods:topic></mods:subject><mods:subject xmlns:xlink="http://www.w3.org/1999/xlink" authority="FAST" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/1151484"><mods:topic>Tissue engineering</mods:topic></mods:subject><mods:recordInfo>
        <mods:recordContentSource authority="marcorg">RPB</mods:recordContentSource>
        <mods:recordCreationDate encoding="iso8601">20160629</mods:recordCreationDate>        
    </mods:recordInfo>
<mods:language xmlns:xlink="http://www.w3.org/1999/xlink"><mods:languageTerm type="code" authority="iso639-2b">eng</mods:languageTerm><mods:languageTerm type="text">English</mods:languageTerm></mods:language><mods:identifier xmlns:xlink="http://www.w3.org/1999/xlink" type="doi">10.7301/Z0V1235D</mods:identifier><mods:accessCondition xmlns:xlink="http://www.w3.org/1999/xlink" type="rights statement" xlink:href="http://rightsstatements.org/vocab/InC/1.0/">In Copyright</mods:accessCondition><mods:accessCondition type="restriction on access">Collection is open for research.</mods:accessCondition><mods:typeOfResource xmlns:xlink="http://www.w3.org/1999/xlink" authority="primo">dissertations</mods:typeOfResource></mods:mods>