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.

Mesoporous bioglass/silk composite scaffolds for bone tissue engineering

In the past 20 years, mesoporous materials have been attracted great attention due to their significant feature of large surface area, ordered mesoporous structure, tunable pore size and volume, and well-defined surface property. They have many potential applications, such as catalysis, adsorption/separation, biomedicine, etc. [1]. Recently, the studies of the applications of mesoporous materials have been expanded into the field of biomaterials science. A new class of bioactive glass, referred to as mesoporous bioactive glass (MBG), was first developed in 2004. This material has a highly ordered mesopore channel structure with a pore size ranging from 5–20 nm [1]. Compared to non-mesopore bioactive glass (BG), MBG possesses a more optimal surface area, pore volume and improved in vitro apatite mineralization in simulated body fluids [1,2]. Vallet-Regí et al. has systematically investigated the in vitro apatite formation of different types of mesoporous materials, and they demonstrated that an apatite-like layer can be formed on the surfaces of Mobil Composition of Matters (MCM)-48, hexagonal mesoporous silica (SBA-15), phosphorous-doped MCM-41, bioglass-containing MCM-41 and ordered mesoporous MBG, allowing their use in biomedical engineering for tissue regeneration [2-4]. Chang et al. has found that MBG particles can be used for a bioactive drug-delivery system [5,6]. Our study has shown that MBG powders, when incorporated into a poly (lactide-co-glycolide) (PLGA) film, significantly enhance the apatite-mineralization ability and cell response of PLGA films. compared to BG [7]. These studies suggest that MBG is a very promising bioactive material with respect to bone regeneration. It is known that for bone defect repair, tissue engineering represents an optional method by creating three-dimensional (3D) porous scaffolds which will have more advantages than powders or granules as 3D scaffolds will provide an interconnected macroporous network to allow cell migration, nutrient delivery, bone ingrowth, and eventually vascularization [8]. For this reason, we try to apply MBG for bone tissue engineering by developing MBG scaffolds. However, one of the main disadvantages of MBG scaffolds is their low mechanical strength and high brittleness; the other issue is that they have very quick degradation, which leads to an unstable surface for bone cell growth limiting their applications. Silk fibroin, as a new family of native biomaterials, has been widely studied for bone and cartilage repair applications in the form of pure silk or its composite scaffolds [9-14]. Compared to traditional synthetic polymer materials, such as PLGA and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), the chief advantage of silk fibroin is its water-soluble nature, which eliminates the need for organic solvents, that tend to be highly cytotoxic in the process of scaffold preparation [15]. Other advantages of silk scaffolds are their excellent mechanical properties, controllable biodegradability and cytocompatibility [15-17]. However, for the purposes of bone tissue engineering, the osteoconductivity of pure silk scaffolds is suboptimal. It is expected that combining MBG with silk to produce MBG/silk composite scaffolds would greatly improve their physiochemical and osteogenic properties for bone tissue engineering application. Therefore, in this chapter, we will introduce the research development of MBG/silk scaffolds for bone tissue engineering.

Strategy in developing cell based therapy for large bone

Regeneration of osseous defects by tissue-engineering approach provides a novel means of treatment utilizing cell biology, materials science, and molecular biology. The concept of in vitro cultured osteoblasts having an ability to induce new bone formation has been demonstrated in the critical size defects using small animal models. The bone derived cells can be incorporated into bioengineered scaffolds and synthesize bone matrix, which on implantation can induce new bone formation. In search of optimal cell delivery materials, the extracellular matrix as cell carriers for the repair and regeneration of tissues is receiving increased attention. We have investigated extracellular matrix formed by osteoblasts in vitro as a scaffold for osteoblasts transplantation and found a mineralized matrix, formed by human osteoblasts in vitro, can initiate bone formation by activating endogenous mesenchymal cells. To repair the large bone defects, osteogenic or stem cells need to be prefabricated in a large three dimensional scaffold usually made of synthetic biomaterials, which have inadequate interaction with cells and lead to in vivo foreign body reactions. The interstitial extracellular matrix has been applied to modify biomaterials surface and identified vitronectin, which binds the heparin domain and RGD (Arg-Gly-Asp) sequence can modulate cell spreading, migration and matrix formation on biomaterials. We also synthesized a tri-block copolymer, methoxy-terminated poly(ethylene glycol)(MPEG)-polyL-lactide(PLLA)-polylysine(PLL) for human osteoblasts delivery. We identified osteogenic activity can be regulated by the molecular weight and composition of the triblock copolymers. Due to the sequential loss of lineage differentiation potential during the culture of bone marrow stromal cells that hinderers their potential clinical application, we have developed a clonal culture system and established several stem cell clones with fast growing and multi-differentiation properties. Using proteomics and subtractive immunization, several differential proteins have been identified and verified their potential application in stem cell characterization and tissue regeneration

Scaffolding large units for small group collaborative learning : a case study.

Undergraduates working in teams can be a problematic endeavour, sometimes exacerbated for the student by poor prior experiences, a predisposition to an individual orientation of assessment, and simply the busyness that now typifies the life of a student. But effort in pedagogical design is worthwhile where team work is often a prerequisite in terms of graduate capabilities, robust learning, increased motivation, and indeed in terms of equipping individuals for emergent knowledge-age work practice, often epitomised by collaborative effort in both blended and virtual contexts. Through an iterative approach, based extensively on the established literature, we have developed a successful scaffold which is workable with a large cohort group (n >800), such that it affords students the lived experience of being a part of a learning network. Individuals within teams work together, to develop individual components that are subsequently aggregated and reified to an overall team knowledge artefact. We describe our case and propose a pedagogical model of scaffolding based on three perspectives: conceptual, rule-based and community-driven. This model provides designers with guidelines for producing and refining assessment tasks for team-based learning.

Regulating for Sustainability : Property Issues

All Australian governments recognize the need to ensure that land and natural resources are used sustainably. In this context, ‘resources’ includes natural resources found on land such as trees and other vegetation, fauna, soil and minerals, and cultural resources found on land such as archaeological sites and artefacts. Regulators use a wide range of techniques to promote sustainability. To achieve their objectives, they may, for example, create economic incentives through bounties, grants and subsidies, encourage the development of self-regulatory codes, or enter into agreements with landowners specifying how the land is to be managed. A common way of regulating is by making administrative orders, determinations or decisions under powers given to regulators by Acts of Parliament (statutes) or by regulations (delegated legislation). Generally the legislation provides for specified rights or duties, and authorises a regulator to make an order or decision to apply the legislative provisions to particular land or cases. For example, legislation might empower a regulator to make an order that requires the owner of a contaminated site to remediate it. When the regulator exercises the power by making an order in relation to particular land, the owner is placed under a statutory duty to remediate. When regulators exercise their statutory powers to manage the use of private land or natural or cultural resources on private land, property law issues can arise. The owner of land has a private property right that the law will enforce against anybody else who interferes with the enjoyment of the right, without legal authority to do so. The law dealing with the enforcement of private property rights forms part of private law. This report focuses on the relationship between the law of private property and the regulation of land and resources by legislation and by administrative decisions made under powers given by legislation (statutory powers).

Crown copyright

Copyright protects much of the creative, cultural, educational, scientific and informational material generated by federal, State/Territory and local governments and their constituent departments and agencies. Governments at all levels develop, manage and distribute a vast array of materials in the form of documents, reports, websites, datasets and databases on CD or DVD and files that can be downloaded from a website. Under the Copyright Act 1968 (Cth), with few exceptions government copyright is treated the same as copyright owned by non-government parties insofar as the range of protected materials and the exclusive proprietary rights attaching to them are concerned. However, the rationale for recognizing copyright in public sector materials and vesting ownership of copyright in governments is fundamentally different to the main rationales underpinning copyright generally. The central justification for recognizing Crown copyright is to ensure that government documents and materials created for public administrative purposes are disseminated in an accurate and reliable form. Consequently, the exclusive rights held by governments as copyright owners must be exercised in a manner consistent with the rationale for conferring copyright ownership on them. Since Crown copyright exists primarily to ensure that documents and materials produced for use in the conduct of government are circulated in an accurate and reliable form, governments should exercise their exclusive rights to ensure that their copyright materials are made available for access and reuse, in accordance with any laws and policies relating to access to public sector materials. While copyright law vests copyright owners with extensive bundles of exclusive rights which can be exercised to prevent others making use of the copyright material, in the case of Crown copyright materials these rights should rarely be asserted by government to deviate from the general rule that Crown copyright materials will be available for “full and free reproduction” by the community at large.

Privacy v IP Litigation : preliminary third party discovery on the Internet

The enforcement of Intellectual Property rights poses one of the greatest current threats to the privacy of individuals online. Recent trends have shown that the balance between privacy and intellectual property enforcement has been shifted in favour of intellectual property owners. This article discusses the ways in which the scope of preliminary discovery and Anton Piller orders have been overly expanded in actions where large amounts of electronic information is available, especially against online intermediaries (service providers and content hosts). The victim in these cases is usually the end user whose privacy has been infringed without a right of reply and sometimes without notice. This article proposes some ways in which the delicate balance can be restored, and considers some safeguards for user privacy. These safeguards include restructuring the threshold tests for discovery, limiting the scope of information disclosed, distinguishing identity discovery from information discovery, and distinguishing information preservation from preliminary discovery.

Using a social networking site such as Facebook, to enhance the feeling of belonging, within a first year nursing cohort of a large university

Recently I asked a first year student how he was coping with the transition from high school to university. The young fellow looked at me and said, “Man, everything is so different!” I smiled and said “like what?” with which he seriously replied, “Well for one thing, no one tells you that you have to wear a hat at lunch time.” I have to admit I was a little amused and surprised by this student’s response, as so often the focus, is placed on getting first year students to engage academically, when it is obvious at times, that even the mere transition in to university life and the culture itself, can be a hurdle. While teaching, within a large first year unit for over 10 years, it has become apparent that students want more connection with not only the peers that they study with, but also with the University as a whole. Dr Krause pointed out in her keynote paper, On Being Strategic about the First Year (2006), that this “sense of belonging is conducive to enhancing engagement, satisfaction with learning and commitment to study”. It has also become evident, that the way in which students want to be able to communicate has changed, with the advent of capabilities such as Instant Messaging via a network and Short Message Service SMS texting via their hand held mobile phones. To be able to chat and feel connected on social networking sites such as Bebo, Facebook and Twitter is not only a way of the future, it is here now and it is here to stay.

Parallel user profiling based on folksonomy for Large Scaled Recommender Systems : an implimentation of Cascading MapReduce

The Large scaled emerging user created information in web 2.0 such as tags, reviews, comments and blogs can be used to profile users’ interests and preferences to make personalized recommendations. To solve the scalability problem of the current user profiling and recommender systems, this paper proposes a parallel user profiling approach and a scalable recommender system. The current advanced cloud computing techniques including Hadoop, MapReduce and Cascading are employed to implement the proposed approaches. The experiments were conducted on Amazon EC2 Elastic MapReduce and S3 with a real world large scaled dataset from Del.icio.us website.

CRE workshop part I : comprehending the context

CRE (Corporate Real Estate) decisions should not simply deal with the management of individual facilities, but should especially be concerned with the relationships that a facility has with the corporate business strategy and with the larger real estate markets. Both the practice and the research of CRE management have historically tended to emphasize real estate issues and ignore the corporation’s business issues, causing real estate strategies to be disconnected from the goal and priorities of the corporation’s senior management. With regard to office cycles, a large number of econometric models have been proposed during the last 20 years. However, evidence from historical data and previous research in the field of real estate forecasting seem to agree only on one thing: the existence of interconnected property cycles that are concentrated on vacancy rates (demand). Vacancy also represents the linkage between the inadequacy of existing CRE strategies and the inability of existing econometric models to correctly forecast office rent cycles. Business cycles, across different industry sectors, have decreased from 5-7 years to 1-3 years today, yet corporations are still entering into leases of 5-10 years, causing hidden vacancy levels to rise. Possibly, once CRE strategies are totally in tune with the overall business, hidden vacancy will fade away providing forecasters with better quality data. The aim of this paper is not to investigate whether and when the supply-side will eventually evolve to provide flexible occupancy arrangements to accommodate corporate agility requirements, but rather to propose a general framework for corporations to improve the decision making process of their CRE executives, while emphasizing the importance of understanding the context as a precondition to effective real estate involvements.

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.

The Law of Real Property Mortgages

This book examines the principles and practice of real estate mortgages in an easily accessible text referenced to all the Australian States. It specifically deals with the major theoretical and practical aspects of the land mortgage including vitiating factors in formation, mortgagees powers and duties and mortgagors’ rights both statutory and other, assignment, insurance and discharge. As a successor to Mortgages Law in Australia, this book adopts an exclusive focus on real estate mortgages in Australia and provides a thorough account of the law through analysis of the plethora of court decisions and statutory provisions in this area. Duncan and Dixon analyse the substance of the mortgage transaction from creation through to rights of enforcement. This analysis includes detailed consideration of the rights and obligations of both mortgagors and mortgagees covering topics such as priorities and tacking, insurance, variation and assignment, rights of discharge, entry into possession, foreclosure and power of sale. In addition, the book contains a separate chapter on factors that may affect the validity and enforcement of a mortgage together with separate consideration of a mortgagee’s right to enforce a guarantee provided on behalf of a mortgagor and the rights and liabilities associated with a receivership regime initiated by a mortgagee. Written for the national market, the book is one of the few substantial works on this subject for practitioners throughout Australia. It is a very accessible text which enables readers to decide whether or not they have a problem and provides primary guidance to its solution. The book has been deliberately, heavily referenced to incorporate statutory references from across Australia and contains extensive case analysis in order to satisfy both these objectives.

Property Agents and Motor Dealers Act : strike three

The Tourism, Racing and Fair Trading (Miscellaneous Provisions) Act 2002 (“the Act”) which was passed on 18 April 2002 contains a number of significant amendments relevant to the operation of the Property Agents and Motor Dealers Act 2000. The main changes relevant to property transactions are: (i) Changes to the process for appointment of a real estate agent and consolidation of the appointment forms; (ii) Additions to the disclosure obligation of agents and property developers; (iii) Simplification of the process for commencing the cooling off period; (iv) Alteration of the common law position concerning when the parties are bound by a contract; (v) Removal of the requirement for a seller’s signature on the warning statement to be witnessed; (vi) Retrospective amendment of s 170 of the Body Corporate and Community Management Act 1997; (vii) Inclusion of a new power to allow inspectors to enter the place of business of a licensee or a marketeer without consent and without a warrant; and (viii) Inclusion of a new power for inspectors to require documents to be produced by marketeers. The majority of the amendments are effective from the date of assent, 24 April 2002, however, some of the amendments do not commence until a date fixed by proclamation. No proclamation has been made at the time of writing (2 May 2002). Where the amendments have not commenced this will be noted in the article. Before providing clients with advice, practitioners should carefully check proclamation details.

Property Agents and Motor Dealers Act : take two

The Property Agents and Motor Dealers Act 2000 commenced on 1 July 2001. Significant changes have now been made to the Act by the Property Agents and Motor Dealers Amendment Act 2001 (“the amending Act”). The amending Act contains two distinct parts. First, ss 11-19 of the amending Act provide for increased disclosure obligations on real estate agents, property developers and lawyers together with an extension of the 5 business day cooling-off period imposed by the original Act to all residential property (other than contracts formed on a sale by auction). These provisions commenced on 29 October 2001. The remaining provisions of the amending Act provide for increased jurisdiction and powers to the Property Agents and Motor Dealers Tribunal (“the Tribunal”) enabling the Tribunal to deal with claims against marketeers. These provisions commenced on the date of assent, 21 September 2001.