Mesenchymal stem cells

Cell based therapies as they apply to tissue engineering and regenerative medicine, require cells capable of self renewal and differentiation, and a prerequisite is to be able to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies therefore figures as an integral part of tissue engineering. Stem cells serve as a reserve for biological repair, having the potential to differentiate into a number of specialised cell types within the body; they therefore represent the most useful candidates for cell based therapies. The primary goal of stem cell research is to produce cells that are both patient specific, as well as having properties suitable for the specific conditions for which they are intended to remedy. From a purely scientific perspective, stem cells allow scientists to gain a deeper understanding of developmental biology and regenerative therapies. Stem cells have acquired a number of uses for applications in regenerative medicine, immunotherapy, gene therapy, but it is in the area of tissue engineering that they generate most excitement, primarily as a result of their capacity for self-renewal and pluripotency. A unique feature of stem cells is their ability to maintain an uncommitted quiescent state in vivo and then, once triggered by conditions such as disease, injury or natural wear or tear, serve as a reservoir and natural support system to replenish lost cells. Although these cells retain the plasticity to differentiate into various tissues, being able to control this differentiation process is still one of the biggest challenges facing stem cell research. In an effort to harness the potential of these cells a number of studies have been conducted using both embryonic/foetal and adult stem cells. The use of embryonic stem cells (ESC) have been hampered by strong ethical and political concerns, this despite their perceived versatility due to their pluripotency. Ethical issues aside, other concerns raised with ESCs relates to the possibility of tumorigenesis, immune rejection and complications with immunosuppressive therapies, all of which adds layers of complications to the application ESC in research and which has led to the search for alternative sources for stem cells. The adult tissues in higher organisms harbours cells, termed adult stem cells, and these cells are reminiscent of unprogrammed stem cells. A number of sources of adult stem cells have been described. Bone marrow is by far the most accessible source of two potent populations of adult stem cells, namely haematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BMSCs). Autologously harvested adult stem cells can, in contrast to embryonic stem cells, readily be used in autografts, since immune rejection is not an issue; and their use in scientific research has not attracted the ethical concerns which have been the case with embryonic stem cells. The major limitation to their use, however, is the fact that adult stem cells are exceedingly rare in most tissues. This fact makes identifying and isolating these cells problematic; bone marrow being perhaps the only notable exception. Unlike the case of HSCs, there are as yet no rigorous criteria for characterizing MSCs. Changing acuity about the pluripotency of MSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to MSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their study in vitro. Also, when MSCs are cultured in vitro, there is a loss of the in vivo microenvironment, resulting in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage numbers in culture, characterized by the onset of senescence related changes. As a consequence, it is necessary to establish protocols for generating large numbers of MSCs but without affecting their differentiation potential. MSCs are capable of differentiating into mesenchymal tissue lineages, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Recent findings indicate that adult bone marrow may also contain cells that can differentiate into the mature, nonhematopoietic cells of a number of tissues, including cells of the liver, kidney, lung, skin, gastrointestinal tract, and myocytes of heart and skeletal muscle. MSCs can readily be expanded in vitro and can be genetically modified by viral vectors and be induced to differentiate into specific cell lineages by changing the microenvironment–properties which makes these cells ideal vehicles for cellular gene therapy. MSCs can also exert profound immunosuppressive effects via modulation of both cellular and innate immune pathways, and this property allows them to overcome the issue of immune rejection. Despite the many attractive features associated with MSCs, there are still many hurdles to overcome before these cells are readily available for use in clinical applications. The main concern relates to in vivo characterization and identification of MSCs. The lack of a universal biomarker, sparse in vivo distribution, and a steady age related decline in their numbers, makes it an obvious need to decipher the reprogramming pathways and critical molecular players which govern the characteristics unique to MSCs. This book presents a comprehensive insight into the biology of adult stem cells and their utility in current regeneration therapies. The adult stem cell populations reviewed in this book include bone marrow derived MSCs, adipose derived stem cells (ASCs), umbilical cord blood stem cells, and placental stem cells. The features such as MSC circulation and trafficking, neuroprotective properties, and the nurturing roles and differentiation potential of multiple lineages have been discussed in details. In terms of therapeutic applications, the strengths of MSCs have been presented and their roles in disease treatments such as osteoarthritis, Huntington’s disease, periodontal regeneration, and pancreatic islet transplantation have been discussed. An analysis comparing osteoblast differentiation of umbilical cord blood stem cells and MSCs has been reviewed, as has a comparison of human placental stem cells and ASCs, in terms of isolation, identification and therapeutic applications of ASC in bone, cartilage regeneration, as well as myocardial regeneration. It is my sincere hope that this book will update the reader as to the research progress of MSC biology and potential use of these cells in clinical applications. It will be the best reward to all contributors of this book, if their efforts herein may in some way help the readers in any part of their study, research, and career development.

Overview of mesenchymal stem cells

Stem cells are unprogrammed cells which possess plasticity and self renewal capability. The term of stem cell was first used to describe cells committed to give rise to germline cells, and to describe proposed progenitor cells of the blood system [1]. A unique feature of stem cell is to remain quiescent in vivo in an uncommitted state. They serve as reservoir or natural support system to replenish cells lost due to disease, injury or aging. When triggered by appropriate signals these cells divide and may become specialized, committed cells; however being able to control this differentiation process still remains one of the biggest challenge in stem cell research [2]. The cell division of stem cells is a distinct aspect of their biology, since this division may be either symmetric or asymmetric. Symmetric division takes place when the stem cells divides and forms two new daughter cells. Asymmetric division is thought to take place only under certain conditions where stem cells divides and gives rise to a daughter cell which remains primitive and does not proliferate, and one committed progenitor cell, which heads down a path of differentiation. Asymmetric division of stem cells helps reparative process, and also ensures that the stem cells pool does not decrease, whereas symmetric division is responsible for stem cells undergoing self renewal and proliferation. The factors which prompt the stem cells to undergo asymmetric division are, however, not well understood, but it is clear that the delicate balance between the self renewal and differentiation is what maintains tissue homeostasis.

Mesenchymal stem cells in osteoarthritis therapy : current status of theory, technology, and applications

Osteoarthritis (OA) is a chronic, non-inflammatory type of arthritis, which usually affects the movable and weight bearing joints of the body. It is the most common joint disease in human beings and common in elderly people. Till date, there are no safe and effective diseases modifying OA drugs (DMOADs) to treat the millions of patients suffering from this serious and debilitating disease. However, recent studies provide strong evidence for the use of mesenchymal stem cell (MSC) therapy in curing cartilage related disorders. Due to their natural differentiation properties, MSCs can serve as vehicles for the delivery of effective, targeted treatment to damaged cartilage in OA disease. In vitro, MSCs can readily be tailored with transgenes with anti-catabolic or pro-anabolic effects to create cartilage-friendly therapeutic vehicles. On the other hand, tissue engineering constructs with scaffolds and biomaterials holds promising biological cartilage therapy. Many of these strategies have been validated in a wide range of in vitro and in vivo studies assessing treatment feasibility or efficacy. In this review, we provide an outline of the rationale and status of stem-cell-based treatments for OA cartilage, and we discuss prospects for clinical implementation and the factors crucial for maintaining the drive towards this goal.

The 3D model of l(IT)eracy and the English curriculum

The field of literacy studies has always been challenged by the changing technologies that humans have used to express, represent and communicate their feelings, ideas, understandings and knowledge. However, while the written word has remained central to literacy processes over a long period, it is generally accepted that there have been significant changes to what constitutes ‘literate’ practice. In particular, the status of the printed word has been challenged by the increasing dominance of the image, along with the multimodal meaning-making systems facilitated by digital media. For example, Gunther Kress and other members of the New London Group have argued that the second half of the twentieth century saw a significant cultural shift from the linguistic to the visual as the dominant semiotic mode. This in turn, they suggest, was accompanied by a cultural shift ‘from page to screen’ as a dominant space of representation (e.g. Cope & Kalantzis, 2000; Kress, 2003; New London Group, 1996). In a similar vein, Bill Green has noted that we have witnessed a shift from the regime of the print apparatus to a regime of the digital electronic apparatus (Lankshear, Snyder and Green, 2000). For these reasons, the field of literacy education has been challenged to find new ways to conceptualise what is meant by ‘literacy’ in the twenty first century and to rethink the conditions under which children might best be taught to be fully literate so that they can operate with agency in today’s world.

The ecological approach to visual perception and the actor performance captured in the gaming landscape

The use of Performance Capture techniques in the creation of games that involve Motion Capture is a relatively new phenomenon. To date there is no prescribed methodology that prepares actors for the rigors of this new industry and as such there are many questions to be answered around how actors navigate these environments successfully when all available training and theoretical material is focused on performance for theatre and film. This article proposes that through a deployment of an Ecological Approach to Visual Perception we may begin to chart this territory for actors and begin to contend with the demands of performing for the motion captured gaming scenario.

Understanding the factors influencing safe and unsafe motorcycle rider intentions

The increasing popularity of motorcycles in Australia is a significant concern as motorcycle riders represent 15% of all road fatalities and an even greater proportion of serious injuries. This study assessed the psychosocial factors influencing motorcycle riders’ intentions to perform both safe and risky riding behaviours. Using an extended theory of planned behaviour (TPB), motorcycle riders (n = 229) from Queensland, Australia were surveyed to assess their riding attitudes, subjective norm (general and specific), perceived behavioural control (PBC), group norm, self-identity, sensation seeking, and aggression, as well as their intentions, in relation to three safe (e.g., handle my motorcycle skilfully) and three risky (e.g., bend road rules to get through traffic) riding behaviours. Although there was variability in the predictors of intention across the behaviours, results revealed that safer rider intentions were most consistently predicted by PBC, while riskier intentions were predicted by attitudes and sensation seeking. The TPB was able to explain a greater proportion of the variance for intentions to perform risky behaviours. Overall, this study has provided insight into the complexity of factors contributing to rider intentions and suggests that different practical strategies need to be adopted to facilitate safer and reduce risky rider decisions.

Critical literacy : foundational notes

This article traces the lineage of critical literacy from Freire through critical pedagogies and discourse analysis. It discusses the need for a contingent definition of critical literacy, given the increasingly sophisticated nature of texts and discourses.

Periodontal regeneration and mesenchymal stem cells

The ultimate goal of periodontal therapy is to regenerate periodontal supporting tissues, but this is hard to achieve as the results of periodontal techniques for regeneration are clinically unpredictable. Stem cells owing to their plasticity and proliferation potential provides a new paradigm for periodontal regeneration. Stem cells from mesenchyme can self renew and generate new dental tissues (including dentin and cementum), alveolar bone and periodontal ligament, and thus they have great potential in periodontal regeneration. This chapter presents an insight into mesenchymal stem cells and their potential use in periodontal regeneration. In this chapter the cellular and molecular biology in periodontal regeneration will be introduced, followed by a range of conventional surgical procedures for periodontal regeneration will be discussed. Mesenchymal stem cells applied in regenerated periodontal tissue and their biological characterizations in vitro will be also introduced. Lastly, the use of mesenchymal stem cell to repair periodontal tissues in large animal models will be also reviewed.

Order supported by law : the enforcement of norms in virtual communities

As online social spaces continue to grow in importance, the complex relationship between users and the private providers of the platforms continues to raise increasingly difficult questions about legitimacy in online governance. This article examines two issues that go to the core of egitimate governance in online communities: how are rules enforced and punishments imposed, and how should the law support legitimate governance and protect participants from the illegitimate exercise of power? Because the rules of online communities are generally ultimately backed by contractual terms of service, the imposition of punishment for the breach of internal rules exists in a difficult conceptual gap between criminal law and the predominantly compensatory remedies of contractual doctrine. When theorists have addressed the need for the rules of virtual communities to be enforced, a dichotomy has generally emerged between the appropriate role of criminal law for 'real' crimes, and the private, internal resolution of 'virtual' or 'fantasy' crimes. In this structure, the punitive effect of internal measures is downplayed and the harm that can be caused to participants by internal sanctions is systemically undervalued.

Strategies for managing osteoarthritis

Background Although there are recommendations for the management of osteoarthritis (OA), little is known about how people with OA actually manage this chronic condition. Purpose The aims of this study were to identify the non-pharmacological and pharmacological therapies most commonly used for the management of hip or knee OA, in a community-based sample of adults, and to compare these with evidence-based recommendations. Methods A questionnaire was mailed to 2200 adult members of Arthritis Queensland living in Brisbane, Australia. It included questions about OA symptoms, management therapies and demographic characteristics. Results Of the 485 participants (192 men, 293 women) with hip or knee OA who completed the questionnaire, most had mild to moderate symptoms. Ninety-six percent of participants (aged 27–95 years) reported using at least one non-pharmacological therapy, and 78% reported using at least one pharmacological therapy. The most common currently used non-pharmacological strategy was range-of-motion exercises (men 52%, women 61%, p=0.05) and the most common frequently used pharmacological strategy was glucosamine/chondroitin (men 51%, women 60%, ns). For the most highly recommended strategies, 65% of men and 54% of women had never attended an information/education course (p=0.04), and fewer than half (46% of women and 42% of men, p=0.03) were frequent users of anti-inflammatory agents. Conclusion The findings suggest that many people with knee or hip OA do not follow the most highly endorsed of the OARSI (Osteoarthritis Research Society International) recommendations for management of OA. Health professionals should be encouraged to recommend evidence-based therapies to their patients.

Using user-friendly telecommunications to improve cardiac and diabetes self-management programme : a pilot study

Previous studies exploring the incidence and readmission rates of cardiac patients admitted to a coronary care unit (CCU) with type 2 diabetes [1] have been undertaken by the first author. Interviews of these patients regarding their experiences in managing their everyday conditions [2] provided the basis for developing the initial cardiac–diabetes self-management programme (CDSMP) [3]. Findings from each of these previous studies highlighted the complexity of self-management for patients with both conditions and contributed to the creation of a new self-management programme, the CDSMP, based on Bandura’s (2004) self-efficacy theory [4]. From patient and staff feedback received for the CDSMP [3], it became evident that further revision of the programme was needed to improve self-management levels of patients and possibility of incorporating methods of information technology (IT). Little is known about the applicability of different methods of technology for delivering self-management programmes for patients with chronic diseases such as those with type 2 diabetes and cardiac conditions. Although there is some evidence supporting the benefits and the great potential of using IT in supporting self-management programmes, it is not strong, and further research on the use of IT in such programmes is recommended [5–7]. Therefore, this study was designed to pilot test feasibility of the CDSMP incorporating telephone and text-messaging as follow-up approaches.

Probabilistic subgroup identification using Bayesian finite mixture modelling : a case study in Parkinson’s disease phenotype identification

This article explores the use of probabilistic classification, namely finite mixture modelling, for identification of complex disease phenotypes, given cross-sectional data. In particular, if focuses on posterior probabilities of subgroup membership, a standard output of finite mixture modelling, and how the quantification of uncertainty in these probabilities can lead to more detailed analyses. Using a Bayesian approach, we describe two practical uses of this uncertainty: (i) as a means of describing a person’s membership to a single or multiple latent subgroups and (ii) as a means of describing identified subgroups by patient-centred covariates not included in model estimation. These proposed uses are demonstrated on a case study in Parkinson’s disease (PD), where latent subgroups are identified using multiple symptoms from the Unified Parkinson’s Disease Rating Scale (UPDRS).

Attribute exclusion strategies in airline choice : accounting for exogenous information on decision maker processing strategies in models of discrete choice

We examine the impact of individual-specific information processing strategies (IPSs) on the inclusion/exclusion of attributes on the parameter estimates and behavioural outputs of models of discrete choice. Current practice assumes that individuals employ a homogenous IPS with regards to how they process attributes of stated choice (SC) experiments. We show how information collected exogenous of the SC experiment on whether respondents either ignored or considered each attribute may be used in the estimation process, and how such information provides outputs that are IPS segment specific. We contend that accounting the inclusion/exclusion of attributes will result in behaviourally richer population parameter estimates.

Implications of the National Rental Affordability Scheme on the valuation of residential property

The provision of shelter is a basic need and in Australia there has been a history of home ownership. However recent economic growth and rising construction costs, particularly over the past decade, has placed home ownership out of reach for some. In response to increased affordability pressures, the Australian Federal Government established the National Rental Affordability Scheme (NRAS) in 2008. The aim of establishing the NRAS initiative is to stimulate the supply of new affordable rental dwellings, targeting 50,000 new properties by June 2012, through the provision of a National Rental Incentive for each “approved” dwelling. To be approved the dwelling must be newly constructed and subsequently rented to eligible low and moderate income households at rentals no greater than 80 percent of market rates. There is a further requirement that the accommodation be provided as part of the scheme for no less than 10 years. The requirement to provide new residential accommodation at below market rentals for no less than 10 years has an impact on value and as such the valuation methodologies employed. To give guidance to valuers this paper investigates the scheme, the impact on value and expectations for the future.

Pedagogies of industry partnership

This chapter discusses the experiences of doctoral students who work across traditional disciplinary and university-industry boundaries. These new contexts for doctoral education are shaping how students are experiencing and responding to requirements for changing knowledge relationships. Drawing on Bernstein's discussion of pedagogic practice as being socially constructed, and his conceptual framework outlining the social implications of the weaker boundaries required for these knowledge relationships, we discuss students' descriptions of their topics, processes and challenges and show their strategies for performing scholarly research across these boundaries as key elements in the nature and achievement of “industry readiness”. In particular, we identify two key elements in the pedagogy of industry partnership: students’ understandings and management of the knowledge relationships involved in this work, and the dispositions they bring to bear in negotiating research and careers across disciplinary and sectoral boundaries.