Identifier

etd-07052014-002034

Degree

Doctor of Philosophy (PhD)

Department

Biomedical and Veterinary Medical Sciences - Comparative Biomedical Sciences

Document Type

Dissertation

Abstract

Utilization of patient-specific stem cells in regenerative medicine provides a novel treatment approach for diseases and disorders. Embryonic stem cells and induced pluripotent stem cells can differentiate into any cells found within the body; however, ethical, technical and safety concerns have to be overcome before they can be used in clinics. Patient-specific stem cells can be isolated from adult tissues with no ethical, fewer technical, and safety concerns. Obtaining tissues for stem cell isolation usually requires invasive procedures, but impacted teeth are often extracted in the clinics and can be used for isolation of dental follicle stem cells (DFSCs). The overall goal of this dissertation is to characterize the osteogenic potential of DFSCs and to explore the possibility of using DFSCs for the treatment of craniofacial defects. In this regard, we first showed that DFSCs can be induced to differentiate primarily toward the osteoblast lineage. Our experiments showed that DFSCs at passages 3 to 5 have a strong osteogenic capability that is reduced during in vitro expansion. Comparing DFSCs with non-stem cell dental follicle cells (DFCs), we determined that dentin matrix protein 1 (DMP1) is highly expressed in DFSCs. Further study suggests that DMP1 is likely necessary to maintain the osteogenic differentiation capability of DFSCs via regulating expression of osteogenic genes. Given that adult stem cells exist in a quiescent state under normal physiological conditions, we attempted to activate DFSCs with heat-stress. Culturing DFSCs under mild heat-stress (39ºC-40ºC) could effectively promote their proliferation and osteogenic differentiation. In the final part of this project, in vivo transplantation experiments were conducted to evaluate the osteogenic potential of DFSCs for treatment of calvarial critical-size defects using a rat model. Bone regeneration was assessed by micro-computed tomography (micro-CT) and histological analysis at 4 and 8 weeks post-transplantation. The results showed that transplantation of DFSCs seeded into PCL scaffold significantly improved bone regeneration. An average of 50% bone recovery was observed with treatment of PCL-DFSC transplantation at 8 weeks. In conclusion, this study found that DFSCs are valuable tissue stem cells possessing strong osteogenic potential that can be used for repairing craniofacial defects.

Date

2014

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Yao, Shaomian

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