- Title Information
- Title
- The Effects of Aging and Chemotherapeutics on
Mesenchymal Stem Cell Regenerative Properties
- Name:
Personal
- Name Part
- Beane, Olivia S
- Role
- Role Term:
Text
- creator
- Origin Information
- Copyright Date
- 2016
- Physical Description
- Extent
- xvii, 235 p.
- digitalOrigin
- born digital
- Note
- Thesis (Ph.D. -- Brown University (2016)
- Name:
Personal
- Name Part
- Darling, Eric
- Role
- Role Term:
Text
- Director
- Name:
Personal
- Name Part
- Ciombor, Deborah
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Hoffman-Kim, Diane
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Franck, Christian
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Darling, Louise
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. Biomedical Engineering
- Role
- Role Term:
Text
- sponsor
- Genre (aat)
- theses
- 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.
- Subject (FAST)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/1763304")
- Topic
- Mesenchymal stem cells
- Subject (FAST)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/800293")
- Topic
- Aging
- Subject (FAST)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/853595")
- Topic
- Chemotherapy
- Subject (FAST)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/1151484")
- Topic
- Tissue engineering
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20160629
- Language
- Language Term:
Code (ISO639-2B)
- eng
- Language Term:
Text
- English
- Identifier:
DOI
- 10.7301/Z0V1235D
- Access Condition:
rights statement
(href="http://rightsstatements.org/vocab/InC/1.0/")
- In Copyright
- Access Condition:
restriction on access
- Collection is open for research.
- Type of Resource (primo)
- dissertations