Worcester Polytechnic Institute Electronic Theses and Dissertations Collection

Title page for ETD etd-090208-143505


Document Typethesis
Author NameMurphy, Megan K
URNetd-090208-143505
TitleFibrin Microthreads Promote Stem Cell Growth for Localized Delivery in Regenerative Therapy
DegreeMS
DepartmentBiomedical Engineering
Advisors
  • Glenn Gaudette, Advisor
  • George Pins, Advisor
  • Marsha Rolle, Advisor
  • Keywords
  • myocardium
  • microthreads
  • fibrin
  • infarct
  • human mesenchymal stem cells
  • Date of Presentation/Defense2008-08-25
    Availability unrestricted

    Abstract

    Recent evidence suggests that delivering human mesenchymal stem cells (hMSCs) to the infarcted heart reduces infarct size and improves ventricular performance. However, cell delivery systems have critical limitations such as inefficient cell retention and poor survival, and lack targeted localization. Our laboratories have recently developed a method to produce discrete fibrin microthreads that can be attached to a needle and delivered to a precise location within the heart wall. We hypothesize that fibrin microthreads will support hMSC proliferation, survival and retention of multipotency, and may therefore facilitate targeted hMSC delivery to injured tissues such as infarcted myocardium. To test this hypothesis, we bundled 100 μm diameter microthreads to provide grooves to encourage initial cell attachment. We seeded hMSCs onto the microthread bundles by applying 50,000 cells in 100 μL of media. The number of cells adhered to the microthreads was determined up to 5 days in culture. Cell density on the fibrin microthreads increased over time in culture, achieving an average density of 730 ± 101 cells/mm2. A LIVE/DEAD assay confirmed that the cells were viable and Ki-67 staining verified the increase in cell number over time was due to proliferation. Additionally, functional differentiation assays proved that the hMSCs cultured on microthreads retained their ability to differentiate into adipocytes and osteocytes. The results of this study demonstrate that delivering 1 to 4 cell seeded microthread bundles to the infarcted rat myocardium has the potential to produce a positive improvement in mechanical function and these microthreads support hMSC proliferation and survival. Additionally these findings suggest that cell-seeded microthreads may serve a platform technology to improve localized delivery of viable cells to infarcted myocardium to promote functional tissue regeneration.

    Files
  • MMurphy.pdf

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