612 research outputs found
An overview of direct somatic reprogramming: The ins and outs of iPSCs
No full textStem cells are classified into embryonic stem cells and adult stem cells. An evolving alternative to conventional stem cell therapies is induced pluripotent stem cells (iPSCs), which have a multi-lineage potential comparable to conventionally acquired embryonic stem cells with the additional benefits of being less immunoreactive and avoiding many of the ethical concerns raised with the use of embryonic material. The ability to generate iPSCs from somatic cells provides tremendous promise for regenerative medicine. The breakthrough of iPSCs has raised the possibility that patient-specific iPSCs can provide autologous cells for cell therapy without the concern for immune rejection. iPSCs are also relevant tools for modeling human diseases and drugs screening. However, there are still several hurdles to overcome before iPSCs can be used for translational purposes. Here, we review the recent advances in somatic reprogramming and the challenges that must be overcome to move this strategy closer to clinical application
Adipose-Derived Stem Cells: A Review of Signaling Networks Governing Cell Fate and Regenerative Potential in the Context of Craniofacial and Long Bone Skeletal Repair
No full textImprovements in medical care, nutrition and social care are resulting in a commendable change in world population demographics with an ever increasing skew towards an aging population. As the proportion of the world’s population that is considered elderly increases, so does the incidence of osteodegenerative disease and the resultant burden on healthcare. The increasing demand coupled with the limitations of contemporary approaches, have provided the impetus to develop novel tissue regeneration therapies. The use of stem cells, with their potential for self-renewal and differentiation, is one potential solution. Adipose-derived stem cells (ASCs), which are relatively easy to harvest and readily available have emerged as an ideal candidate. In this review, we explore the potential for ASCs to provide tangible therapies for craniofacial and long bone skeletal defects, outline key signaling pathways that direct these cells and describe how the developmental signaling program may provide clues on how to guide these cells in vivo. This review also provides an overview of the importance of establishing an osteogenic microniche using appropriately customized scaffolds and delineates some of the key challenges that still need to be overcome for adult stem cell skeletal regenerative therapy to become a clinical reality
A surgical delivery system for targeted cancer gene therapy : the potential therapeutic role of genetically modified microvascular free flaps in the management of primary tumours
No full textTHESIS 8880Gene therapy has generated interest for the treatment of soft tissue malignancies. It offers the theoretical promise of delivering cytotoxic, immunomodulatory, or anti- angiogenic genes to produce proteins targeting tumour cells. The initial excitement generated by gene therapy has been tempered by the disappointing results of clinical trials. Some of the major barriers preventing gene therapy from achieving clinical use include the inability to accurately target the viral vector, insufficient levels of transgene expression, transient expression of the desired gene, and systemic host toxicity. This aim of this study was to address some of these issues by using a novel technique to transduce microvascular free tissue ex vivo. This approach limits systemic toxicity while also allowing a more targeted method of gene therapy delivery and would be useful after oncologic surgery for soft tissue cancers because many of these patients require microvascular reconstructions to repair the ablative defect
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Planning and design of the urban park: A study of use patterns at Fort Lowell Park and the creation of new design guidelines for park development in Tucson, Arizona
No full textThis thesis will study Fort Lowell Park, a typical district park in Tucson, Arizona. Through a survey of park users, the park itself will be assessed according to its positive and negative aspects. The survey itself will seek to capture the thoughts, beliefs, and recreational needs of the typical park user in Tucson. Through the compilation and interpretation of survey results, and with the assistance of case studies involving cities investing in parks and open spaces, the author of this thesis expects to produce new guidelines not only for the improvement of Fort Lowell Park, but also for the planning and design of new urban parks in the Tucson metropolitan area. These new guidelines will not only improve the quality of recreational experiences in the City of Tucson, but will also contribute to the economic, social, and quality of life variables which make a city an attractive place in which to live
Concise Review: Adipose-Derived Stromal Cells for Skeletal Regenerative Medicine
No full textAbstract
As the average age of the population grows, the incidence of osteoporosis and skeletal diseases continues to rise. Current treatment options for skeletal repair include immobilization, rigid fixation, alloplastic materials, and bone grafts, all which have significant limitations, especially in the elderly. Adipose-derived stromal cells (ASCs) represent a readily available abundant supply of mesenchymal stem cells, which demonstrate the ability to undergo osteogenesis in vitro and in vivo, making ASCs a promising source of skeletal progenitor cells. Current protocols allow for the harvest of over one million cells from only 15 ml of lipoaspirate. Despite the clinical use of ASCs to treat systemic inflammatory diseases, no large human clinical trials exist using ASCs for skeletal tissue engineering. The aim of this review is to define ASCs, to describe the isolation procedure of ASCs, to review the basic biology of their osteogenic differentiation, discuss cell types and scaffolds available for bone tissue engineering, and finally, to explore imaging of ASCs and their potential future role in human skeletal tissue engineering efforts.</jats:p
Activation of FGF signaling mediates proliferative and osteogenic differences between neural crest derived frontal and mesoderm parietal derived bone.
No full textAs a culmination of efforts over the last years, our knowledge of the embryonic origins of the mammalian frontal and parietal cranial bones is unambiguous. Progenitor cells that subsequently give rise to frontal bone are of neural crest origin, while parietal bone progenitors arise from paraxial mesoderm. Given the unique qualities of neural crest cells and the clear delineation of the embryonic origins of the calvarial bones, we sought to determine whether mouse neural crest derived frontal bone differs in biology from mesoderm derived parietal bone.BrdU incorporation, immunoblotting and osteogenic differentiation assays were performed to investigate the proliferative rate and osteogenic potential of embryonic and postnatal osteoblasts derived from mouse frontal and parietal bones. Co-culture experiments and treatment with conditioned medium harvested from both types of osteoblasts were performed to investigate potential interactions between the two different tissue origin osteoblasts. Immunoblotting techniques were used to investigate the endogenous level of FGF-2 and the activation of three major FGF signaling pathways. Knockdown of FGF Receptor 1 (FgfR1) was employed to inactivate the FGF signaling.Our results demonstrated that striking differences in cell proliferation and osteogenic differentiation between the frontal and parietal bone can be detected already at embryonic stages. The greater proliferation rate, as well as osteogenic capacity of frontal bone derived osteoblasts, were paralleled by an elevated level of FGF-2 protein synthesis. Moreover, an enhanced activation of FGF-signaling pathways was observed in frontal bone derived osteoblasts. Finally, the greater osteogenic potential of frontal derived osteoblasts was dramatically impaired by knocking down FgfR1.Osteoblasts from mouse neural crest derived frontal bone displayed a greater proliferative and osteogenic potential and endogenous enhanced activation of FGF signaling compared to osteoblasts from mesoderm derived parietal bone. FGF signaling plays a key role in determining biological differences between the two types of osteoblasts
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