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.

Arts-based research in design education

There is an urgent need in terms of changing world conditions to move beyond the dualist paradigm that has traditionally informed design research, education and practice. Rather than attempt to reduce uncertainty, novelty and complexity as is the conventional approach, an argument is presented in this article that seeks to exploit these qualities through a reconceptualisation of design in creative as well as systematic, rigorous and ethical terms. Arts-based research, which 'brings together the systematic and rigorous qualities of inquiry with the creative and imaginative qualities of the arts', is presented as being central to this reconceptualisation. This is exemplified in the application of art-informed inquiry in a research unit for graduating tertiary-level interior design students. The application is described in this article and is shown to rely substantially on the image and its capacity to open up and reveal new possibilities and meaning.

Experiential ethics education for IT professionals

This chapter presents a new approach to IT ethics education that may be used by teachers in academic institutions, employees responsible for promoting ethics in organisations and individuals wanting to pursue their own professional development. Experiential ethics education emphasises deep learning that prompts a changed experience of ethics. We first consider how this approach complements other ways of engaging in ethics education. We then explore what it means to strive for experiential change and offer a model which may be useful in pursuing IT professional ethics education in this way.

Service-learning within higher education : rhizomatic interconnections between university and the real world

This paper discusses Service-learning within an Australian higher education context as pedagogy to teach about inclusive education. Using Deleuze and Guattari’s (1987) model of the rhizome, this study conceptualises pre-service teachers’ learning experiences as multiple, hydra and continuous. Data from reflection logs of pre-service teachers highlight how the learning experience allowed them to gain insights in knowledge as socially just, ethical and inclusive. The paper concludes by arguing the need to consider Service-learning as integral to university education for pre-service teachers.

Benchmarking local E-Government

Increasingly, almost everything we do in our daily lives is being influenced by information and communications technologies (ICTs) including the Internet. The task of governance is no exception with an increasing number of national, state, and local governments utilizing ICTs to support government operations, engage citizens, and provide government services. As with other things, the process of governance is now being prefixed with an “e”. E-governance can range from simple Web sites that convey basic information to complex sites that transform the customary ways of delivering all sorts of government services. In this respect local e-government is the form of e-governance that specifically focuses on the online delivery of suitable local services by local authorities. In practice local e-government reflects four dimensions, each one dealing with the functions of government itself. The four are: (a) e-services, the electronic delivery of government information, programs, and services often over the Internet; (b) e-management, the use of information technology to improve the management of government. This might range from streamlining business processes to improving the flow of information within government departments; (c) e-democracy the use of electronic communication vehicles, such as e-mail and the Internet, to increase citizen participation in the public decision-making process; (d) e-commerce, the exchange of money for goods and services over the Internet which might include citizens paying taxes and utility bills, renewing vehicle registrations, and paying for recreation programs, or government buying office supplies and auctioning surplus equipment (Cook, LaVigne, Pagano, Dawes, & Pardo, 2002). Commensurate with the rapid increase in the process of developing e-governance tools, there has been an increased interest in benchmarking the process of local e-governance. This benchmarking, which includes the processes involved in e-governance as well as the extent of e-governance adoption or take-up is important as it allows for improved processes and enables government agencies to move towards world best practice. It is within this context that this article discusses benchmarking local e-government. It brings together a number of discussions regarding the significance of benchmarking, best practices and actions for local e-government, and key elements of a successful local e-government project.

Enhancing professional ethics : service-learning in teacher education

The ethical conduct of professionals has been the focus of increasing scrutiny over the past several decades as members of the public, the media, professional bodies, and legislative authorities have struggled to define ethical behaviour in times of governmental change, increasing internationalisation, globalised communications, threats of terrorism, and the challenges of developments in science and medicine (e.g., Demmke & Bossaert, 2004). National governments and transnational bodies have responded to these concerns about ethics and corruption through measures such as the United Nations Convention Against Corruption (United Nations Office on Drugs and Crime, 2004), Transparency International’s annual corruption index (2010) and Queensland’s Public Sector Ethics Act 1994 (Queensland Parliament 1994). Similarly, academic interest in ethics and its application across a range of domains(e.g., business, health care, social welfare, criminal justice, law, journalism, defence, environment, and media) has also increased. To illustrate, in 1993, a non-partisan, non-profit national umbrella organisation, the Australian Association for Professional and Applied Ethics, was formed following a conference concerned with the teaching of ethics (http://www.arts.unsw.edu.au./aapae/about_aapae/about_aapae.htm), while a recent review of the Excellence in Research for Australian rankings of national and international academic journals revealed that 16 journals related to ethics had received the top ratings of A* or A (Australian Research Council, 2009). In this chapter we examine professional ethics and argue, with specific reference to the context of pre-service teacher education, that Service-learning is one way of enhancing emerging professionals’ understanding of ethics.

Does pornography harm young people?

In recent debates about the regulation of technologies that deliver pornographic content, the greatest concerns have been about the increasing ease with which young people can access such material. Because of the ethical difficulties in researching this topic, little data has been available on the potential harm done to young people by exposure to pornography. This paper gathers a number of data sources that address this issue indirectly—including the results of our own survey of over 1000 consumers of pornography—to explore this issue. Research shows that healthy sexual development includes natural curiosity about sexuality. Retrospective studies show that accidental exposure to real-life scenes of sexuality does not harm children. Our survey shows that age of first exposure to pornography does not correlate with negative attitudes towards women. Studies with non-explicit representations of sexuality show that young people who seek out sexualised representations tend to be those with a pre-existing interest in sexuality. These studies also suggest that current generations of children are no more sexualised than previous generations, that they are not innocent about sexuality, and that a key negative effect of this knowledge is the requirement for them to feign ignorance in order to satisfy adults’ expectations of them. Research also suggests important differences between pre- and post-pubescent attitudes towards pornography, and that pornography is not addictive.

Ethics and Socially Responsible Investment : A Philosophical Approach

This volume breaks new ground by approaching Socially Responsible Investment (SRI) as an explicitly ethical practice in financial markets. The work explains the philosophical and practical shortcomings of ‘long term shareholder value’ and the origins and conceptual structure of SRI, and links its pursuit to both its deeper philosophical foundations and the broader, multi-dimensional global movement towards greater social responsibility in global markets. Interviews with fund managers in the Australian SRI sector generate recommendations for better integrating ethics into SRI practice via ethically informed engagement with invested companies, and an in-depth discussion of the central practical SRI issue of fiduciary responsibility strengthens the case in favour of SRI. The practical and ethical theoretical perspectives are then brought together to sketch out an achievable ideal for SRI worldwide, in which those who are involved in investment and business decisions become part of an ‘ethical chain’ of decision makers linking the ultimate owners of capital with the business executives who frame, advocate and implement business strategies. In between there are investment advisors, fund managers, business analysts and boards. The problem lies in the fact that the ultimate owners are discouraged from considering their own values, or even their own long term interests, whilst the others often look only to short term interests. The solution lies in the latter recognising themselves as links in the ethical chain.

Adam Smith's Dinner

The Future of Financial Regulation is an edited collection of papers presented at a major conference at the University of Glasgow in Spring 2009. It draws together a variety of different perspectives on the international financial crisis which began in August 2007 and later turned into a more widespread economic crisis following the collapse of Lehman Brothers in the Autumn of 2008. Spring 2009 was in many respects the nadir since valuations in financial markets had reached their low point and crisis management rather than regulatory reform was the main focus of attention. The conference and book were deliberately framed as an attempt to re-focus attention from the former to the latter. The first part of the book focuses on the context of the crisis, discussing the general characteristics of financial crises and the specific influences that were at work during this time. The second part focuses more specifically on regulatory techniques and practices implicated in the crisis, noting in particular an over-reliance on the capacity of regulators and financial institutions to manage risk and on the capacity of markets to self-correct. The third part focuses on the role of governance and ethics in the crisis and in particular the need for a common ethical framework to underpin governance practices and to provide greater clarity in the design of accountability mechanisms. The final part focuses on the trajectory of regulatory reform, noting the considerable potential for change as a result of the role of the state in the rescue and recuperation of the financial system and stressing the need for fundamental re-appraisal of business and regulatory models. This informative book will be of interest to financial regulators and theorists, commercial and financial law practitioners, and academics involved in the law and economics of regulation.

Re-conceiving the good life : the key to sustainable globalisation

Resource-intensive, high-carbon, Western lifestyles are frequently criticised as unsustainable and deeply unsatisfying. However, these lifestyles are still attractive to the majority of Westerners and to a high proportion of the developing world’s middle classes. This paper argues that the imminent threat of catastrophic climate change constitutes an immediate political, economic and ethical challenge for citizens of the developed world that cannot be tackled by appeals to asceticism or restraint. There can be no solution to climate change until sustainable conceptions of the good life are developed that those in the west want to live and which others might want to live. While the ultimate solution to climate change is the development of low carbon lifestyles, it is important that government initiatives, governance arrangements and economic incentives support rather than undermine that search. Like the global financial crisis, the climate change crisis also demonstrates what happens when weaknesses in national, corporate and professional governance are exacerbated by weaknesses in global governance. In tackling the latter, it is critical the mistakes now evidenced in the former are avoided – including a rethinking of carbon market and carbon tax alternatives. It is also critical that individuals must take responsibility for their actions as consumers, voters and investors.

Defending the sanctity of life principle : a reply to John Keown

This article is a response to Professor Keown’s criticism of my paper “Finding a Way Through the Ethical and Legal Maze: Withdrawal of Medical Treatment and Euthanasia” (2005) 13 (3) Medical Law Review 357. The article takes up and responds to a number of criticisms raised by Keown in an attempt to further the debate concerning the moral and legal status of withdrawing life-sustaining measures, its distinction from euthanasia, and the implications of the lawfulness of withdrawal for the principle of the sanctity of life.

Professions without borders : global ethics and the international rule of law

The emergence of strong sovereign states after the Treaty of Westphalia turned two of the most cosmopolitan professions (law and arms) into two of the least cosmopolitan. Sovereign states determined the content of the law within their borders – including which, if any, ecclesiastical law was to be applied; what form of economic regulation was adopted; and what, if any, international law applied. Similarly, states sought to ensure that all military force was at their disposal in national armies. The erosion of sovereignty in a post-Westphalian world may significantly reverse these processes. The erosion of sovereignty is likely to have profound consequences for the legal profession and the ethics of how, and for what ends, it is practised. Lawyers have played a major role in the civilization of sovereign states through the articulation and institutionalisation of key governance values – starting with the rule of law. An increasingly global profession must take on similar tasks. The same could be said of the military. This essay will review the concept of an international rule of law and its relationship to domestic conceptions and outline the task of building the international rule of law and the role that lawyers can and should play in it.

Reconceiving the good life : the key to sustainable globalisation

Resource-intensive, high-carbon, Western lifestyles are frequently criticised as unsustainable and deeply unsatisfying. However, these lifestyles are still attractive to the majority of Westerners and to a high proportion of the developing world’s middle classes. This paper argues that the imminent threat of catastrophic climate change constitutes an immediate political, economic and ethical challenge for citizens of the developed world that cannot be tackled by appeals to asceticism or restraint. There can be no solution to climate change until sustainable conceptions of the good life are developed that those in the west want to live and which others might want to live. While the ultimate solution to climate change is the development of low carbon lifestyles, it is important that government initiatives, governance arrangements and economic incentives support rather than undermine that search. Like the global financial crisis, the climate change crisis also demonstrates what happens when weaknesses in national, corporate and professional governance are exacerbated by weaknesses in global governance. In tackling the latter, it is critical the mistakes now evidenced in the former are avoided – including a rethinking of carbon market and carbon tax alternatives. It is also critical that individuals must take responsibility for their actions as consumers, voters and investors.

Monitoring mesenchymal stem cell cultures using image processing and pattern recognition techniques

Stem cells have attracted tremendous interest in recent times due to their promise in providing innovative new treatments for a great range of currently debilitating diseases. This is due to their potential ability to regenerate and repair damaged tissue, and hence restore lost body function, in a manner beyond the body's usual healing process. Bone marrow-derived mesenchymal stem cells or bone marrow stromal cells are one type of adult stem cells that are of particular interest. Since they are derived from a living human adult donor, they do not have the ethical issues associated with the use of human embryonic stem cells. They are also able to be taken from a patient or other donors with relative ease and then grown readily in the laboratory for clinical application. Despite the attractive properties of bone marrow stromal cells, there is presently no quick and easy way to determine the quality of a sample of such cells. Presently, a sample must be grown for weeks and subject to various time-consuming assays, under the direction of an expert cell biologist, to determine whether it will be useful. Hence there is a great need for innovative new ways to assess the quality of cell cultures for research and potential clinical application. The research presented in this thesis investigates the use of computerised image processing and pattern recognition techniques to provide a quicker and simpler method for the quality assessment of bone marrow stromal cell cultures. In particular, aim of this work is to find out whether it is possible, through the use of image processing and pattern recognition techniques, to predict the growth potential of a culture of human bone marrow stromal cells at early stages, before it is readily apparent to a human observer. With the above aim in mind, a computerised system was developed to classify the quality of bone marrow stromal cell cultures based on phase contrast microscopy images. Our system was trained and tested on mixed images of both healthy and unhealthy bone marrow stromal cell samples taken from three different patients. This system, when presented with 44 previously unseen bone marrow stromal cell culture images, outperformed human experts in the ability to correctly classify healthy and unhealthy cultures. The system correctly classified the health status of an image 88% of the time compared to an average of 72% of the time for human experts. Extensive training and testing of the system on a set of 139 normal sized images and 567 smaller image tiles showed an average performance of 86% and 85% correct classifications, respectively. The contributions of this thesis include demonstrating the applicability and potential of computerised image processing and pattern recognition techniques to the task of quality assessment of bone marrow stromal cell cultures. As part of this system, an image normalisation method has been suggested and a new segmentation algorithm has been developed for locating cell regions of irregularly shaped cells in phase contrast images. Importantly, we have validated the efficacy of both the normalisation and segmentation method, by demonstrating that both methods quantitatively improve the classification performance of subsequent pattern recognition algorithms, in discriminating between cell cultures of differing health status. We have shown that the quality of a cell culture of bone marrow stromal cells may be assessed without the need to either segment individual cells or to use time-lapse imaging. Finally, we have proposed a set of features, that when extracted from the cell regions of segmented input images, can be used to train current state of the art pattern recognition systems to predict the quality of bone marrow stromal cell cultures earlier and more consistently than human experts.

From allure to ethics : design as a ‘creative industry'

In this chapter I look at the question of design and ethics in a situation where design as a set of related economic practices has been re-positioned as a key identifier for a new kind of ideas-driven industry - the creative industries. Previously marginal to cultural policy in the form of applied arts, in the creative industries agenda design became a privileged meeting place, or indeed broker, for art and industry, economy and commerce. I explore the new kinds of ethical challenges this brings.