LoSurdo, Jessica Lindsay
(2009)
MECHANICALLY- AND BIOCHEMICALLY-INDUCED DIFFERENTIATIONOF BONE MARROW MESENCHYMAL STEM CELLS TO SMOOTH MUSCLECELLS IN A THREE-DIMENSIONAL FIBRIN MATRIX.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Bone marrow mesenchymal stem cells (BMMSCs) may serve as an alternative source toterminally differentiated cells for tissue engineering applications. Our group has demonstratedthat BMMSCs subjected to a mechanical environment may differentiate toward a smooth musclecell (SMC) phenotype. Growth factors in conjunction with mechanical stimulation have beenshown 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-actinexpression in SMCs when compared to mechanical strain alone. Taken together, this previouswork suggests that mechanical and chemical factors may work together to promotedifferentiation of BMMSCs toward an SMC phenotype. Consequently, the hypothesis of thecurrent work is that uniaxial cyclic strain and biochemical stimulation with TGF-â willdifferentiate 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 tocyclic mechanical strains and frequencies physiologically consistent with the arterial system, incombination with chemical stimulation with TGF-â. Changes in morphology, proliferation,collagen production, and qualitative protein expression were assessed to determine if there wereany synergistic effects between mechanical and chemical stimulation.Results revealed that BMMSCs subjected to both mechanical and biochemicalstimulation 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 incollagen production when compared to control groups. These results support our hypothesis andsuggest that combined mechanical and biochemical stimulation may be important in stem cellbasedregenerative medicine applications involving SMCs.Future work will evaluate SMC gene expression and functionality to better define the roleof mechanical and biochemical stimuli in differentiating BMMSCs toward a terminallydifferentiated SMC phenotype.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
28 January 2009 |
| Date Type: |
Completion |
| Defense Date: |
5 August 2008 |
| Approval Date: |
28 January 2009 |
| Submission Date: |
1 December 2008 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
MSBeng - Master of Science in Bioengineering |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
biochemical; differentiation; mechanical; mesenchymal stem cells; smooth muscle cells |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-12012008-150712/, etd-12012008-150712 |
| Date Deposited: |
10 Nov 2011 20:07 |
| Last Modified: |
15 Nov 2016 13:52 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/9922 |
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