Haemopoietic stem and progenitor cells from bone marrow and cord blood are well characterised with respect to their phenotype, growth in clonal assays, responsiveness to cytokine stimulation, receptor profile and their ability to sustain multilineage engraftment of receptive hosts in animal models of transplantation and of course, clinically in the treatment of some haemopoietic and immunological disorders. It is generally accepted that cells bearing the CD34+ phenotype are enriched for the most primitive of haemopoietic stem cells that possess the cardinal features of self-renewal and multipotency. However, the molecular mechanisms, the spectrum of expressed genes that give rise to the physical characteristics of haemopoietic progenitor cells are not well understood. Furthermore, although CD34+ cells from different sources (bone marrow, cord blood, mobilised peripheral blood) share many common features, there are also significant differences. (For complete abstract open document)

Title page, contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / The growth plate is a cartilaginous structure located at the proximal and distal ends of immature long bones, which contributes to longitudinal growth through the process of endochondral ossification. Cartilage has a limited ability to regenerate and in children, injury to the the growth plate can result in limb length discrepancies and angular deformity, due to formation of a bone bridge at the damaged site which disturbs structure and function of the growth plate. Current treatments of the abnormalities arising from growth plate arrest involve surgical correction once the deformities have manifested. To date, there is no biological based therapy for the repair of injured/damaged growth plate cartilage. Mesenchymal stem cells (MSC) are self renewable mulitpotential progenitor cells with the capacity to differentiate toward the chondrogenic lineage. Since their discovery, significant interest has been generated in the potential application of these cells for cartilage regeneration. In this study, the ability of autologous bone marrow mesenchymal stem cells to regenerate growth plate cartilage in a sheep model was examined. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1330837 / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

Discovery of the ability of mesenchymal stem cells (MSCs) to differentiate into cells of non-mesodermal tissues, particularly neuronal cells, have raised the possibility of utilising MSCs in regenerative/reparative therapies for neurological disorders. However, a number of hurdles remain to be resolved. This thesis aims to address some of these issues by investigating the characteristics of bone marrow-derived human MSCs (hMSCs) during long-term culture, the potential of hMSCs to differentiate in vitro toward the neuronal lineage under the influence of cytokines, and the effects of intracerebral transplantation in the hemiparkinsonian rat model. During expansion culture hMSCs were found to display the expected characteristics of MSC populations, and also constitutively expressed neural and pluripotency markers simultaneously with mesodermal markers. Analysis of hMSC long-term subcultivation revealed an optimal period for commencing neuronal differentiation (first 6-8 passages), and also showed the absence of spontaneous neural differentiation. Application of neural-inducing cytokines and culture conditions resulted in the generation of an immature neuronal-like phenotype by hMSCs. Through live cell microscopy it was demonstrated for the first time that cytokine-based hMSC neuronal differentiation occurs through active and dynamic cellular processes involving outgrowth and motility of cellular extensions. In addition, single- and multiple-stage cytokine-based strategies for inducing dopaminergic neuronal-like cells from hMSCs were investigated. These studies revealed that FGF-2 and EGF exerted the greatest benefits for hMSC neuronal differentiation. Undifferentiated and neuronal-primed hMSCs were transplanted intracerebrally into the striatum and substantia nigra of cyclosporine-treated hemiparkinsonian rats. Grafted hMSCs could be clearly identified at 1-day and 7-days post-transplantation; however, grafts were gradually lost over time, with complete absence by 21-days. Co-transplantation with olfactory ensheathing cells, neuronal-priming prior to grafting, and nigral as well as striatal grafting could not provide engraftment and differentiation advantages. Immunohistological analysis demonstrated the presence of innate inflammatory responses (microglia and astrocyte activation) at graft sites, fibronectin deposition by hMSCs, and lack of endogenous host neurogenesis. The results of my PhD work indicate that cytokine-based culture methods are capable of differentiating hMSCs to an immature neuronal-like phenotype, and host-mediated innate inflammatory responses may be a key contributing factor for the failure of in vivo hMSC engraftment.

Discovery of the ability of mesenchymal stem cells (MSCs) to differentiate into cells of non-mesodermal tissues, particularly neuronal cells, have raised the possibility of utilising MSCs in regenerative/reparative therapies for neurological disorders. However, a number of hurdles remain to be resolved. This thesis aims to address some of these issues by investigating the characteristics of bone marrow-derived human MSCs (hMSCs) during long-term culture, the potential of hMSCs to differentiate in vitro toward the neuronal lineage under the influence of cytokines, and the effects of intracerebral transplantation in the hemiparkinsonian rat model. During expansion culture hMSCs were found to display the expected characteristics of MSC populations, and also constitutively expressed neural and pluripotency markers simultaneously with mesodermal markers. Analysis of hMSC long-term subcultivation revealed an optimal period for commencing neuronal differentiation (first 6-8 passages), and also showed the absence of spontaneous neural differentiation. Application of neural-inducing cytokines and culture conditions resulted in the generation of an immature neuronal-like phenotype by hMSCs. Through live cell microscopy it was demonstrated for the first time that cytokine-based hMSC neuronal differentiation occurs through active and dynamic cellular processes involving outgrowth and motility of cellular extensions. In addition, single- and multiple-stage cytokine-based strategies for inducing dopaminergic neuronal-like cells from hMSCs were investigated. These studies revealed that FGF-2 and EGF exerted the greatest benefits for hMSC neuronal differentiation. Undifferentiated and neuronal-primed hMSCs were transplanted intracerebrally into the striatum and substantia nigra of cyclosporine-treated hemiparkinsonian rats. Grafted hMSCs could be clearly identified at 1-day and 7-days post-transplantation; however, grafts were gradually lost over time, with complete absence by 21-days. Co-transplantation with olfactory ensheathing cells, neuronal-priming prior to grafting, and nigral as well as striatal grafting could not provide engraftment and differentiation advantages. Immunohistological analysis demonstrated the presence of innate inflammatory responses (microglia and astrocyte activation) at graft sites, fibronectin deposition by hMSCs, and lack of endogenous host neurogenesis. The results of my PhD work indicate that cytokine-based culture methods are capable of differentiating hMSCs to an immature neuronal-like phenotype, and host-mediated innate inflammatory responses may be a key contributing factor for the failure of in vivo hMSC engraftment.

Thesis (Ph.D.)--Tufts University, 2004. / Adviser: David L. Kaplan. Submitted to the Dept. of Biotechnology Engineering. Includes bibliographical references (leaves 162-222). Access restricted to members of the Tufts University community. Also available via the World Wide Web;

Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "August 2007" Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available in print.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Adelaide, Dept. of Orthopaedics Surgery and Trauma, 1998. / Bibliography: leaves 152-223.

Thesis (M.S.)--University of Delaware, 2008. / Principal faculty advisor: Robert A. Sikes, Dept. of Biological Sciences. Includes bibliographical references.