Bone marrow mesenchymal stem cells (BMMSCs) may serve as an alternative source to
terminally differentiated cells for tissue engineering applications. Our group has demonstrated
that BMMSCs subjected to a mechanical environment may differentiate toward a smooth muscle
cell (SMC) phenotype. Growth factors in conjunction with mechanical stimulation have been
shown in prior work to have a significant effect in regulating SMC phenotype in 2D.
Simultaneous stimulation with mechanical strain and TGF-â has been shown to increase á-actin
expression in SMCs when compared to mechanical strain alone. Taken together, this previous
work suggests that mechanical and chemical factors may work together to promote
differentiation of BMMSCs toward an SMC phenotype. Consequently, the hypothesis of the
current work is that uniaxial cyclic strain and biochemical stimulation with TGF-â will
differentiate BMMSCs towards an SMC-like lineage in a synergistic manner in 3D.
To evaluate this hypothesis, rat BMMSCs suspended in a fibrin gel were subjected to
cyclic mechanical strains and frequencies physiologically consistent with the arterial system, in
combination with chemical stimulation with TGF-â. Changes in morphology, proliferation,
collagen production, and qualitative protein expression were assessed to determine if there were
any synergistic effects between mechanical and chemical stimulation.
Results revealed that BMMSCs subjected to both mechanical and biochemical
stimulation led to an increase in production of contractile machinery intrinsic to terminally-differentiated SMCs, an increase in expression of SMC marker proteins, and an increase in
collagen production when compared to control groups. These results support our hypothesis and
suggest that combined mechanical and biochemical stimulation may be important in stem cellbased
regenerative medicine applications involving SMCs.
Future work will evaluate SMC gene expression and functionality to better define the role
of mechanical and biochemical stimuli in differentiating BMMSCs toward a terminally
differentiated SMC phenotype.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-12012008-150712 |
| Date | 28 January 2009 |
| Creators | LoSurdo, Jessica Lindsay |
| Contributors | Dr. Bridget Deasy, Dr. Kacey Marra, Dr. David Vorp, Dr. Kimimasa Tobita |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-12012008-150712/ |
| Rights | restricted, 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 University of Pittsburgh 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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