The incidence and long-term effects of traumatic brain injury (TBI) make it a major
healthcare and socioeconomic concern. Cell transplantation may be an alternative
therapy option to target prolonged neurological deficits; however, safety and efficacy of
the cells must be determined. Bone marrow-derived mesenchymal stem cells (MSCs)
are an accessible and expandable cell source which circumvent the many of the
accessibility and ethical concerns associated with fetal tissues. A major impediment to
recent clinical trials for cell therapies in the central nervous system has been the lack of
consistency in functional recovery where some patients receive great benefits while
others experience little, if any, effect (Watts and Dunnett 2000; Lindvall and Bjorklund
2004). There are many possible explanations for this patient-to-patient variability
including genetic and environmental factors, surgical techniques, and donor cell
variability. Of these, the most easily addressable is to increase the reproducibility of
donor cells by standardizing the isolation and pre-transplantation protocols, which is the
central goal of this dissertation. First, we present an animal study in which transplants of
MSCs and neural stem cells (NSCs) were given to brain-injured mice, however, the
efficacy of the treatment had high variability between individual subjects. Second, we
designed a method to produce MSC-spheres and characterize them in vitro. Last, we
employed an in vitro 3-D culture testbed as a pre-transplant injury model to assess the
effects of the MSC-spheres on neural cells. The electrophysiological function of the
uninjured testbed was assessed, and then MSC-spheres were injected into the testbed
and apoptosis of the host cells were measured. The results of this study contribute to our
understanding of how extracellular context may influence MSC-spheres and develop
MSCs as a donor cell source for transplantation.
| Identifer | oai:union.ndltd.org:GATECH/oai:smartech.gatech.edu:1853/16168 |
| Date | 09 July 2007 |
| Creators | Irons, Hillary Rose |
| Publisher | Georgia Institute of Technology |
| Source Sets | Georgia Tech Electronic Thesis and Dissertation Archive |
| Detected Language | English |
| Type | Dissertation |
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