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Efficacy of clonal progenitor cells from dental pulp and bone marrow to regenerate craniofacial mineralised tissue structures

Harrington, Jodie 2014. Efficacy of clonal progenitor cells from dental pulp and bone marrow to regenerate craniofacial mineralised tissue structures. PhD Thesis, Cardiff University.
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The current clinical choice for bone regeneration is autologous bone grafts from the iliac crest. The associated drawbacks, however, in terms of morbidity and low cell number following tissue harvest, have led to search for alternative stromal cell sources in conjunction with native tissue matrix components. For mineralised tissue engineering, alternative to mesenchymal bone marrow stromal cells (BMSCs), mesenchymal dental pulp stromal cells (DPSCs) have been proposed due to high colony formation and differentiation potential. Understanding which stromal population is exemplar for rapid and effective regeneration is paramount, and central to efficient bone regeneration is providing the optimal microenvironment to the characterised stem cells. This thesis compared clonal BMSCs that formed few and large colonies, with DPSCs that formed many small colonies. Comparison of clonal differentiation along adipogenesis, chondrogenesis, with particular attention on their capacity for osteogenic formation, showed BMSCs were multipotent, while DPSCs only displayed uni- and bi- potency (osteogenic inclusive). Neither VCAM1 nor MCAM mesenchymal marker expression related to differentiation capacity. Stromal clones exposed to whole-protein tissue matrix extracts from bone (BME) and tooth (TME), found in vitro mineralisation by BMSCs and DPSCs with TME, but mineralisation by DPSCs only with BME. BMSC and DPSC clones were also assessed on bone- and tooth- slabs to replicate in vivo injury of fracture and caries, respectively. BMSCs and DPSCs displayed proliferation and differentiation on tissue-slabs, but BMSCs did not attach to tooth-slab, which was probable of tissue differences in supportive extracellular proteins. In summary, results indicated BMSCs are more primitive stromal cells closely related to the mother stem cell, while DPSCs are more lineage committed and are suggestive of transit-amplifying cells; indicative of their in vivo roles, that is, bone is remodeled constantly and tooth responds to injury only. While much research is still required, DPSCs and their matrix-proteins potentially offer an easily accessible and viable alternative for craniofacial bone reconstruction.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Dentistry
Subjects: R Medicine > RK Dentistry
Uncontrolled Keywords: Craniofacial mineralised tissue structures; dental pulp; bone marrow.
Funders: MRC Capacity Building Studentship
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 07:40

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