Bone tissue engineering utilizing adult stem cells in biologically functionalized hydrogels

Repair of large bone defects remains a clinical challenge for orthopedic surgeons. Current treatment strategies such as autograft and allograft are limited by the amount of available tissue in the case of the former, and failure of revascularization effecting engraftment in the case of the latter. Tissue engineering offers an alternative approach to this challenging clinical problem. The general principle of tissue engineering for bone regeneration prescribes delivery of osteoinductive factors to induce an endogenous response within the host to repair a defect that will not normally heal. One such tissue engineering approach is cell based therapy and this is attractive in the cases of patients with a lack of endogenous osteoprogenitors cells due to volumetric loss of tissue/ageing. Stem cell therapy has emerged as a possible alternative to current treatment modalities, however many challenges to clinical translation remain. Central to these challenges for bone tissue engineering are lingering questions of which cells to use and how to effectively deliver those cells. The goal of this thesis was to elucidate more effective ways to enhance bone repair utilizing adult stem cells. First, we investigated adipose derived stem cells (ADSCs) as a viable cell source for bone tissue engineering. Upon isolation, adipose derived stem cells are a heterogeneous population of multipotent cells predisposed to adipogenic differentiation. We developed an enrichment protocol that demonstrated the osteogenic potential of ADSCs can be enhanced in a dose dependent manner with resveratrol, which had been demonstrated to up-regulate Runx-2 expression. This enrichment strategy produced an effective method to enhance the osteogenic potential of ADSCs while avoiding cell sorting and gene therapy techniques, thus bypassing the use of xenogenic factors to obtain an enriched source of osteoprogenitor cells. This protocol was also used to investigate differences between human and rat ADSCs and demonstrated that rat ADSCs have a higher osteogenic potential than human ADSCs in vitro. The second major thrust of this thesis was to develop an injectable hydrogel system to facilitate bone formation in vivo. Both a synthetic and a naturally based polymer system was investigated, the results of which demonstrated that the naturally based alginate hydrogel was a more effective vehicle for both cell viability in vitro and bone formation in vivo. Our results also demonstrated that despite the ability to increase the osteogenic potential of ADSCs in vitro with resveratrol treatment, this was insufficient to induce bone formation in vivo. However, the inclusion of bone marrow mesenchymal stem cells (BMMSCs) in BMP-2 functionalized alginate hydrogels resulted in significantly greater mineralization than acellular hydrogels. Finally, the effect of timing of delivery of therapeutics to a non-healing segmental bone defect in the femur was investigated. We hypothesized that delivery of biologics after the initial inflammation response caused by injury to the host tissue would result in greater regeneration of tissue in terms of newly formed bone. Contrary to our initial hypothesis, these experiments demonstrated that delayed implantation of therapeutics has a detrimental effect on the overall healing response. It was, however, demonstrated that the inclusion of BMMSCs results in greater bone volume regenerated in the defect site over acellular hydrogels. In conclusion, this work has rigorously investigated the use of adipose derived stem cells for bone tissue engineering, and further produced an injectable hydrogel system for stem cell based bone tissue engineering. This work also demonstrated that the inclusion of adult stem cells, specifically BMMSCs, can enhance the regeneration response in a non-healing bone defect model relative to acellular hydrogel.PhDCommittee Chair: Robert E. Guldberg; Committee Member: Alexandra Peister; Committee Member: Andres J. Garcia; Committee Member: Barbara D. Boyan; Committee Member: Zvi Schwart

Kacey Carlson Oral History

Oral histories created by University of Kansas students, staff and faculty as part of the Religion in Kansas Project are archived at http://hdl.handle.net/1808/12524 in KU ScholarWorks, the digital repository of the University of Kansas.Oral history interview with Kacey Carlson conducted by Kaitlin Dosier and Jeremy Adkison in Lawrence, Kansas, on October 25, 2010. In this interview, Kacey Carlson, owner of the store Village Witch in Lawrence, Kansas, describes the history and tenets of Wicca, as well as the organizational structure of the Wiccan community. She describes aspects of a variety of Wiccan rituals. She also discusses her discovery of her identity as a witch, and the process of being intiatied into membership in a coven. This interview was conducted for the Religion in Kansas course taught at the University of Kansas by Dr. Timothy Miller in the fall of 2010.Friends of the Department of Religious Studie

Sleep Disorders in Childhood Neurogenetic Disorders

Genetic advances in the past three decades have transformed our understanding and treatment of many human diseases including neurogenetic disorders. Most neurogenetic disorders can be classified as “rare disease,” but collectively neurogenetic disorders are not rare and are commonly encountered in general pediatric practice. The authors decided to select eight relatively well-known neurogenetic disorders including Down syndrome, Angelman syndrome, Prader–Willi syndrome, Smith–Magenis syndrome, congenital central hypoventilation syndrome, achondroplasia, mucopolysaccharidoses, and Duchenne muscular dystrophy. Each disorder is presented in the following format: overview, clinical characteristics, developmental aspects, associated sleep disorders, management and research/future directions

How Managers Influence Subordinates: An Empirical Study of Downward Influence Tactics

An empirical study of managerial influence tactics is described using a structured interview process. Two hundred and fifty‐seven usable narrative accounts of downward influence attempts were obtained using this approach. Respondents also reported the nature of the influence attempt, the reasons for success or failure, whether other people were used, and the long‐term consequences of the influence attempt. These categories derived, described successful and unsuccessful attempts by a wide variety of managers in both private and public sector organisations, large and small. Influence tactics were organised into 17 categories by a systematic and well‐established process. One way chi‐square tests were used to analyse categorised responses. Generally it was found that influence tactic success was more likely when associated with the initiation of new tasks or goals and more likely to fail when trying to eliminate subordinate violation of rules, procedures, or policies. There was a trend for more threatening tactics to be more closely associated with unsuccessful than successful influence attempts. The data suggest that short‐term influence tactic success may be obscured in the research by the use of multiple tactics and by long‐term relationships and that unsuccessful influence attempts may result in the deterioration of interpersonal relationships

Policy Profiles Vol. 2 No. 4 September 2002

Policy Profiles is a publication of the Center for Governmental Studies, Northern Illinois University, and may be reproduced in its entirety with attribution to the Center for Governmental Studies, Northern Illinois University, DeKalb, Illinois.A View of Elementary School Problems in Poor Neighborhoods by Three Elementary School Principal