Regenerative medicine has the potential to revolutionize how medical professionals approach combating and treating disease. Over the past several decades, human mesenchymal stem cells (hMSCs) have become one of the most promising cell sources for regenerative medicine due to their autologous availability, self-renewal capacity, angiogenic effect, immunomodulatory effects, and multi-lineage differentiation potential. However, the individuals who would gain the most from stem cell-based therapies are typically those of advanced age, and the hMSCs they would otherwise provide are accompanied by detrimental abnormalities such as reduced self-renewal and differentiation potentials, thereby limiting their therapeutic efficacy. Furthermore, hMSC-mediated tissue regeneration would require exhaustive in vitro expansion to achieve sufficient numbers, and serially-expanded hMSCs demonstrate passage-associated abnormalities.
This dissertation project aimed at tackling a significant issue in clinical translation of hMSCs, namely looking for material compositions that promote hMSC stem cell health for ex vivo expansion. A library of combinatorial copolymers utilizing FDA-approved synthetic polymers poly(ε-caprolactone) (PCL) and poly(ethylene glycol) (PEG) was synthesized and then fabricated into thin spin-coated films for cell culture. hMSC phenotype was characterized across the copolymer library and the copolymer surface features were interrogated by x-ray scattering and super resolution imaging methods. An ideal candidate copolymer was identified followed by verifying a molecular mechanism for the pro-therapeutic hMSC phenotype and demonstrating the universal effect of the copolymer by culturing patient-derived hMSC instead of commercial hMSCs. These findings will contribute to future biomaterial design to enable effective translation and scalability of regenerative medicine strategies using autologous hMSCs.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-02062017-152357 |
| Date | 08 February 2017 |
| Creators | Balikov, Daniel Adam |
| Contributors | Hak-Joon Sung, Matthew Lang, Justin Turner, Todd Giorgio, Aaron Bowman |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-02062017-152357/ |
| Rights | restrictone, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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