114 resultados para Endosteal niche


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The determinants and key mechanisms of cancer cell osteotropism have not been identified, mainly due to the lack of reproducible animal models representing the biological, genetic and clinical features seen in humans. An ideal model should be capable of recapitulating as many steps of the metastatic cascade as possible, thus facilitating the development of prognostic markers and novel therapeutic strategies. Most animal models of bone metastasis still have to be derived experimentally as most syngeneic and transgeneic approaches do not provide a robust skeletal phenotype and do not recapitulate the biological processes seen in humans. The xenotransplantation of human cancer cells or tumour tissue into immunocompromised murine hosts provides the possibility to simulate early and late stages of the human disease. Human bone or tissue-engineered human bone constructs can be implanted into the animal to recapitulate more subtle, species-specific aspects of the mutual interaction between human cancer cells and the human bone microenvironment. Moreover, the replication of the entire "organ" bone makes it possible to analyse the interaction between cancer cells and the haematopoietic niche and to confer at least a partial human immunity to the murine host. This process of humanisation is facilitated by novel immunocompromised mouse strains that allow a high engraftment rate of human cells or tissue. These humanised xenograft models provide an important research tool to study human biological processes of bone metastasis.

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From the early-to-mid 2000s, the Australian horror film production sector has achieved growth and prosperity of a kind not seen since its heyday of the 1980s. Australian horror films can be traced back to the early 1970s, when they experienced a measure of commercial success. However, throughout the twenty-first-century Australian horror gained levels of international recognition that have surpassed the cult status enjoyed by some of the films in the 1970s and 1980s. In recent years, Australia has emerged as a significant producer of breakout, cult, and solid B-grade horror films, which have circulated in markets worldwide. Australian horror’s recent successes have been driven by one of its distinguishing features: its international dimensions. As this chapter argues, the Australian horror film production sector is an export-oriented industry that relies heavily on international partnerships and presales (the sale of distribution rights prior to a film’s completion), and on its relationships with overseas distributors. Yet, these traits vary from film to film as the sector is comprised of several distinct domains of production activity, from guerrilla films destined for niche video markets like specialist cult video stores and online mail-order websites to high(er)-end pictures made for theatrical markets. Furthermore, the content and style of Australian horror movies has often been tailored for export. While some horror filmmakers have sought to play up the Australianness of their product, others have attempted to pass off their films as faux-American or as placeless films effaced of national reference points.

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A finely-tuned innate immune response plays a pivotal role in protecting host against bacterial invasion during periodontal disease progression. Hyperlipidemia has been suggested to exacerbate periodontal health condition. However, the underlying mechanism has not been addressed. In the present study, we investigated the effect of hyperlipidemia on innate immune responses to periodontal pathogen Porphyromonas gingivalis infection. Apolipoprotein E-deficient and wild-type mice at the age of 20 weeks were used for the study. Peritoneal macrophages were isolated and subsequently used for the study of viable P. gingivalis infection. ApoE−/− mice demonstrated inhibited iNOS production and impaired clearance of P. gingivalis in vitro and in vivo; furthermore, ApoE−/− mice displayed disrupted cytokine production pattern in response to P. gingivalis, with a decreased production of tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β and monocyte chemotactic protein-1. Microarray data demonstrated that Toll-like receptor (TLR) and NOD-like receptor (NLR) pathway were altered in ApoE−/− mice macrophages; further analysis of pattern recognition receptors (PRRs) demonstrated that expression of triggering receptors on myeloid cells-1 (TREM-1), an amplifier of the TLR and NLR pathway, was decreased in ApoE−/− mice macrophages, leading to decreased recruitment of NF-κB onto the promoters of the TNF-α and IL-6. Our data suggest that in ApoE−/− mice hyperlipidemia disrupts the expression of PRRs, and cripples the host’s capability to generate sufficient innate immune response to P. gingivalis, which may facilitate immune evasion, subgingival colonization and establishment of P. gingivalis in the periodontal niche.

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Purpose – The purpose of this paper is to investigate information communications technologies (ICT)-mediated inclusion and exclusion in terms of sexuality through a study of a commercial social networking web site for gay men. Design/methodology/approach – The paper uses an approach based on technological inscription and the commodification of difference to study Gaydar, a commercial social networking site. Findings – Through the activities, events and interactions offered by Gaydar, the study identifies a series of contrasting identity constructions and market segmentations that are constructed through the cyclic commodification of difference. These are fuelled by a particular series of meanings attached to gay male sexualities which serve to keep gay men positioned as a niche market. Research limitations/implications – The research centres on the study of one, albeit widely used, web site with a very specific set of purposes. The study offers a model for future research on sexuality and ICTs. Originality/value – This study places sexuality centre stage in an ICT-mediated environment and provides insights into the contemporary phenomenon of social networking. As a sexualised object, Gaydar presents a semiosis of politicised messages that question heteronormativity while simultaneously contributing to the definition of an increasingly globalised, commercialised and monolithic form of gay male sexuality defined against ICT

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Few science fiction films have been made in Australia by Australians for Australian audiences, with most of the handful of locally-produced films made since the mid-1990s. Yet there has always been a solid Australian audience for non-Australian science fiction films and a strong international niche audience for the genre. While Australia has provided below-the-line crews and heads of departments (cinematographers, production designers, and so on) for many non-Australian science fiction films produced domestically, few Australian film directors have specialised in the genre. This is somewhat surprising considering that Alex Proyas achieved a degree of international success for his gothic science fiction film Dark City (1998), and George Miller achieved international fame following the worldwide success of Mad Max II (1981). Although the science fiction element of Mad Max II is tenuous – and even more so in the case of the original Mad Max (George Miller, 1979) – Miller is credited with creating a new (sub)genre which incorporates science fiction elements and has been widely imitated internationally: the dystopian, post-apocalyptic movie. Nevertheless, Australia has only produced a small number of science fiction movies. In addition to the above films, key titles include: Mad Max Beyond Thunderdome (George Miller, 1985), Shirley Thompson versus the Aliens (Jim Sharman, 1972), The Time Guardian (Brian Hannant, 1987), The Chain Reaction (Ian Barry, 1980) and, more recently, Knowing (Alex Proyas, 2009), Daybreakers (Michael and Peter Spierig, 2009), and Iron Sky (Timo Vuorensola, 2012).

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This paper aims to contribute to an understanding of what actually takes place during consulting engagements. It draws on data collected from a qualitative case study of eight engagements by a niche consultancy in Australia to describe how consultants actively engage boundary crossing processes to address knowledge boundaries encountered during formal interactions with clients. While consultants actively managed knowledge boundary processes during interactions, by applying techniques such as evoking an ‘ideal state’ for clients, the engagements also yielded many missed opportunities for knowledge transformation.

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Chlamydia trachomatis infections of the male and female reproductive tracts are the world's leading sexually transmitted bacterial disease, and can lead to damaging pathology, scarring and infertility. The resolution of chlamydial infection requires the development of adaptive immune responses to infection, and includes cell-mediated and humoral immunity. Whilst cluster of differentiation (CD)4+ T cells are known to be essential in clearance of infection [1], they are also associated with immune cell infiltration, autoimmunity and infertility in the testes [2-3]. Conversely, antibodies are less associated with inflammation, are readily transported into the reproductive tracts, and can offer lumenal neutralization of chlamydiae prior to infection. Antibodies, or immunoglobulins (Ig), play a supportive role in the resolution of chlamydial infections, and this thesis sought to define the function of IgA and IgG, against a variety of chlamydial antigens expressed during the intracellular and extracellular stages of the chlamydial developmental cycle. Transport of IgA and IgG into the mucosal lumen is facilitated by receptor-mediated transcytosis yet the expression profile (under normal conditions and during urogenital chlamydial infection) of the polymeric immunoglobulin receptor (pIgR) and the neonatal Fc receptor (FcRn) remains unknown. The expression profile of pIgR and FcRn in the murine male reproductive tract was found to be polarized to the lower and upper reproductive tract tissues respectively. This demonstrates that the two receptors have a tissue tropism, which must be considered when targeting pathogens that colonize different sites. In contrast, the expression of pIgR and FcRn in the female mouse was found to be distributed in both the upper and lower reproductive tracts. When urogenitally infected with Chlamydia muridarum, both male and female reproductive tracts up-regulated expression of pIgR and down-regulated expression of FcRn. Unsurprisingly, the up-regulation of pIgR increased the concentration of IgA in the lumen. However, down-regulation of FcRn, prevented IgG uptake and led to an increase or pooling of IgG in lumenal secretions. As previous studies have identified the importance of pIgR-mediated delivery of IgA, as well as the potential of IgA to bind and neutralize intracellular pathogens, IgA against a variety of chlamydial antigens was investigated. The protection afforded by IgA against the extracellular antigen major outer membrane protein (MOMP), was found to be dependent on pIgR expression in vitro and in vivo. It was also found that in the absence of pIgR, no protection was afforded to mice previously immunized with MOMP. The protection afforded from polyclonal IgA against the intracellular chlamydial antigens; inclusion membrane protein A (IncA), inclusion membrane proteins (IncMem) and secreted chlamydial protease-like activity factor (CPAF) were produced and investigated in vitro. Antigen-specific intracellular IgA was found to bind to the respective antigen within the infected cell, but did not significantly reduce inclusion formation (p > 0.05). This suggests that whilst IgA specific for the selected antigens was transported by pIgR to the chlamydial inclusion, it was unable to prevent growth. Similarly, immunization of male mice with intracellular chlamydial antigens (IncA or IncMem), followed by depletion CD4+ T cells, and subsequent urogenital C. muridarum challenge, provided minimal pIgR-mediated protection. Wild type male mice immunized with IncA showed a 57 % reduction (p < 0.05), and mice deficient in pIgR showed a 35 % reduction (p < 0.05) in reproductive tract chlamydial burden compared to control antigen, and in the absence of CD4+ T cells. This suggests that pIgR and secretory IgA (SIgA) were playing a protective role (21 % pIgR-mediated) in unison with another antigen-specific immune mechanism (36 %). Interestingly, IgA generated during a primary respiratory C. muridarum infection did not provide a significant amount of protection to secondary urogenital C. muridarum challenge. Together, these data suggest that IgA specific for an extracellular antigen (MOMP) can play a strong protective role in chlamydial infections, and that IgA targeting intracellular antigens is also effective but dependent on pIgR expression in tissues. However, whilst not investigated here, IgA targeting and blocking other intracellular chlamydial antigens, that are more essential for replication or type III secretion, may be more efficacious in subunit vaccines. Recently, studies have demonstrated that IgG can neutralize influenza virus by trafficking IgG-bound virus to lysosomes [4]. We sought to determine if this process could also traffic chlamydial antigens for degradation by lysosomes, despite Chlamydia spp. actively inhibiting fusion with the host endocytic pathway. As observed in pIgR-mediated delivery of anti-IncA IgA, FcRn similarly transported IgG specific for IncA which bound the inclusion membrane. Interestingly, FcRn-mediated delivery of anti-IncA IgG significantly decreased inclusion formation by 36 % (p < 0.01), and induced aberrant inclusion morphology. This suggests that unlike IgA, IgG can facilitate additional host cellular responses which affect the intracellular niche of chlamydial growth. Fluorescence microscopy revealed that IgG also bound the inclusion, but unlike influenza studies, did not induce the recruitment of lysosomes. Notably, anti-IncA IgG recruited sequestosomes to the inclusion membrane, markers of the ubiquitin/proteasome pathway and major histocompatibility complex (MHC) class I loading. To determine if the protection against C. muridarum infection afforded by IncA IgG in vitro translated in vivo, wild type mice and mice deficient in functional FcRn and MHC-I, were immunized, depleted of CD4+, and urogenitally infected with C. muridarum. Unlike in pIgR-deficient mice, the protection afforded from IncA immunization was completely abrogated in mice lacking functional FcRn and MHC-I/CD8+. Thus, both anti-IncA IgA and IgG can bind the inclusion in a pIgR and FcRn-mediated manner, respectively. However, only IgG mediates a higher reduction in chlamydial infection in vitro and in vivo suggesting more than steric blocking of IncA had occurred. Unlike anti-MOMP IgA, which reduced chlamydial infection of epithelial cells and male mouse tissues, IgG was found to enhance infectivity in vitro, and in vivo. Opsonization of EBs with MOMP-IgG enhanced inclusion formation of epithelial cells in a MOMP-IgG dose-dependent and FcRn-dependent manner. When MOMP-IgG opsonized EBs were inoculated into the vagina of female mice, a small but non-significant (p > 0.05) enhancement of cervicovaginal C. muridarum shedding was observed three days post infection in mice with functional FcRn. Interestingly, infection with opsonized EBs reduced the intensity of the peak of infection (day six) but protracted the duration of infection by 60 % in wild type mice only. Infection with EBs opsonized in IgG also significantly increased (p < 0.05) hydrosalpinx formation in the oviducts and induced lymphocyte infiltration uterine horns. As MOMP is an immunodominant antigen, and is widely used in vaccines, the ability of IgG specific to extracellular chlamydial antigens to enhance infection and induce pathology needs to be considered. Together, these data suggest that immunoglobulins play a dichotomous role in chlamydial infections, and are dependent on antigen specificity, FcRn and pIgR expression. FcRn was found to be highly expressed in upper male reproductive tract, whilst pIgR was dominantly expressed in the lower reproductive tract. Conversely, female mice expressed FcRn and pIgR in both the lower and upper reproductive tracts. In response to a normal chlamydial infection, pIgR is up-regulated increasing secretory IgA release, but FcRn is down-regulated preventing IgG uptake. Similarly to other studies [5-6], we demonstrate that IgA and IgG generated during primary chlamydial infections plays a minor role in recall immunity, and that antigen-specific subunit vaccines can offer more protection. We also show that both IgA and IgG can be used to target intracellular chlamydial antigens, but that IgG is more effective. Finally, IgA against the extracellular antigen MOMP can afford protection, whist IgG plays a deleterious role by increasing infectivity and inducing damaging immunopathology. Further investigations with additional antigens or combination subunit vaccines will enhance our understanding the protection afforded by antibodies against intracellular and extracellular pathogenic antigens, and help improve the development of an efficacious chlamydial vaccine.

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Since its launch in 2006, Twitter has turned from a niche service to a mass phenomenon. By the beginning of 2013, the platform claims to have more than 200 million active users, who “post over 400 million tweets per day” (Twitter, 2013). Its success is spreading globally; Twitter is now available in 33 different languages, and has significantly increased its support for languages that use non-Latin character sets. While Twitter, Inc. has occasionally changed the appearance of the service and added new features—often in reaction to users’ developing their own conventions, such as adding ‘#’ in front of important keywords to tag them—the basic idea behind the service has stayed the same: users may post short messages (tweets) of up to 140 characters and follow the updates posted by other users. This leads to the formation of complex follower networks with unidirectional as well as bidirectional connections between individuals, but also between media outlets, NGOs, and other organisations. While originally ‘microblogs’ were perceived as a new genre of online communication, of which Twitter was just one exemplar, the platform has become synonymous with microblogging in most countries. A notable exception is Sina Weibo, popular in China where Twitter is not available. Other similar platforms have been shut down (e.g., Jaiku), or are being used in slightly different ways (e.g., Tumblr), thus making Twitter a unique service within the social media landscape.

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Over the past decade, social media have gone through a process of legitimation and official adoption, and they are now becoming embedded as part of the official communications apparatus of many commercial and public-sector organisations— in turn, providing platforms like Twitter with their own sources of legitimacy. Arguably, the demonstrated utility of social media platforms and tools in times of crisis—from civil unrest and violent crime through to natural disasters like bushfires, earthquakes, and floods—has been a crucial driver of this newfound legitimacy. In the mid-2000s, user-created content and ‘Web 2.0’ platforms were known to play a role in crisis communication; back then, the involvement of extra-institutional actors in providing and sharing information around such events involved distributed, ad hoc, or niche platforms (like Flickr), and was more likely to be framed as ‘citizen journalism’ or ‘crowdsourcing’ (see, for example, Liu, Palen, Sutton, Hughes, & Vieweg, 2008, on the then-emerging role of photo-sharing in disasters). Since then, the dramatically increased take-up of mainstream social media platforms like Facebook and Twitter means that the pool of potential participants in online crisis communication has broadened to include a much larger proportion of the general population, as well as traditional media and official emergency response organisations.

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Much academic writing on pornography focuses on the genre’s exceptionalism (the ways in which it is different from other forms of culture). This paper rather focuses on its typicality as a Creative Industry. As with other Creative Industries, in the production and distribution of pornography it is producers who make most money. While a small number of on-camera performers become wealthy and powerful the majority lack creative control and are poorly paid. The careers of performers are typically short examples of “nomadic labour”. Many creative workers are involved in the production of pornography apart those in front of the camera, and the skills of these behind-the-camera creatives can be transferable across sectors. Like other Creative Industries, the pornography business is facing challenges from increased digitalization and globalization; and like other Creative Industries the solutions to these challenges lie in branding, niche marketing, and exploiting new technological possibilities.

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Introduction. Stem cells are regularly cultured under normoxic conditions. However, the physiological oxygen tension in the stem cell niche is known to be as low as 1-2% oxygen, suggesting that hypoxia has a distinct impact on stem cell maintenance. Periodontal ligament cells (PDLCs) and dental pulp cells (DPCs) are attractive candidates in dental tissue regeneration. It is of great interest to know whether hypoxia plays a role in maintaining the stemness and differentiation capacity of PDLCs and DPCs. Methods. PDLCs and DPCs were cultured either in normoxia (20% O2) or hypoxia (2% O2). Cell viability assays were performed and the expressions of pluripotency markers (Oct-4, Sox2, and c-Myc) were detected by qRT-PCR and western blotting. Mineralization, glycosaminoglycan (GAG) deposition, and lipid droplets formation were assessed by Alizarin red S, Safranin O, and Oil red O staining, respectively. Results. Hypoxia did not show negative effects on the proliferation of PDLCs and DPCs. The pluripotency markers and differentiation potentials of PDLCs and DPCs significantly increased in response to hypoxic environment. Conclusions. Our findings suggest that hypoxia plays an important role in maintaining the stemness and differentiation capacity of PDLCs and DPCs.

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Big Data presents many challenges related to volume, whether one is interested in studying past datasets or, even more problematically, attempting to work with live streams of data. The most obvious challenge, in a ‘noisy’ environment such as contemporary social media, is to collect the pertinent information; be that information for a specific study, tweets which can inform emergency services or other responders to an ongoing crisis, or give an advantage to those involved in prediction markets. Often, such a process is iterative, with keywords and hashtags changing with the passage of time, and both collection and analytic methodologies need to be continually adapted to respond to this changing information. While many of the data sets collected and analyzed are preformed, that is they are built around a particular keyword, hashtag, or set of authors, they still contain a large volume of information, much of which is unnecessary for the current purpose and/or potentially useful for future projects. Accordingly, this panel considers methods for separating and combining data to optimize big data research and report findings to stakeholders. The first paper considers possible coding mechanisms for incoming tweets during a crisis, taking a large stream of incoming tweets and selecting which of those need to be immediately placed in front of responders, for manual filtering and possible action. The paper suggests two solutions for this, content analysis and user profiling. In the former case, aspects of the tweet are assigned a score to assess its likely relationship to the topic at hand, and the urgency of the information, whilst the latter attempts to identify those users who are either serving as amplifiers of information or are known as an authoritative source. Through these techniques, the information contained in a large dataset could be filtered down to match the expected capacity of emergency responders, and knowledge as to the core keywords or hashtags relating to the current event is constantly refined for future data collection. The second paper is also concerned with identifying significant tweets, but in this case tweets relevant to particular prediction market; tennis betting. As increasing numbers of professional sports men and women create Twitter accounts to communicate with their fans, information is being shared regarding injuries, form and emotions which have the potential to impact on future results. As has already been demonstrated with leading US sports, such information is extremely valuable. Tennis, as with American Football (NFL) and Baseball (MLB) has paid subscription services which manually filter incoming news sources, including tweets, for information valuable to gamblers, gambling operators, and fantasy sports players. However, whilst such services are still niche operations, much of the value of information is lost by the time it reaches one of these services. The paper thus considers how information could be filtered from twitter user lists and hash tag or keyword monitoring, assessing the value of the source, information, and the prediction markets to which it may relate. The third paper examines methods for collecting Twitter data and following changes in an ongoing, dynamic social movement, such as the Occupy Wall Street movement. It involves the development of technical infrastructure to collect and make the tweets available for exploration and analysis. A strategy to respond to changes in the social movement is also required or the resulting tweets will only reflect the discussions and strategies the movement used at the time the keyword list is created — in a way, keyword creation is part strategy and part art. In this paper we describe strategies for the creation of a social media archive, specifically tweets related to the Occupy Wall Street movement, and methods for continuing to adapt data collection strategies as the movement’s presence in Twitter changes over time. We also discuss the opportunities and methods to extract data smaller slices of data from an archive of social media data to support a multitude of research projects in multiple fields of study. The common theme amongst these papers is that of constructing a data set, filtering it for a specific purpose, and then using the resulting information to aid in future data collection. The intention is that through the papers presented, and subsequent discussion, the panel will inform the wider research community not only on the objectives and limitations of data collection, live analytics, and filtering, but also on current and in-development methodologies that could be adopted by those working with such datasets, and how such approaches could be customized depending on the project stakeholders.

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This paper highlights the hypercompetitive nature of the current pharmacy landscape in Australia and to suggest either a superior level of differentiation strategy or a focused differentiation strategy targeting a niche market as two viable, alternative business models to cost leadership for small, independent community pharmacies. A description of the Australian health care system is provided as well as background information on the current community pharmacy environment in Australia. The authors propose a differentiation or focused differentiation strategy based on cognitive professional services (CPS) which must be executed well and of a superior quality to competitors' services. Market research to determine the services valued by target customers and that they are willing to pay for is vital. To achieve the superior level of quality that will engender high patient satisfaction levels and loyalty, pharmacy owners and managers need to develop, maintain and clearly communicate service quality specifications to the staff delivering these services. Otherwise, there will be a proliferation of pharmacies offering the same professional services with no evident service differential. However, to sustain competitive advantage over the long-term, these smaller, independent community pharmacies will need to exploit a broad core competency base in order to be able to continuously introduce new sources of competitive advantage. With the right expertise, the authors argue that smaller, independent community pharmacies can successfully deliver CPS and sustain profitability in a hypercompetitive market.

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The objective of this paper is to explore the relationship between dynamic capabilities and different types of online innovations. Building on qualitative data from the publishing industry, our analysis revealed that companies that had relatively strong dynamic capabilities in all three areas (sensing, seizing and reconfiguration) seem to produce innovations that combine their existing capabilities on either the market or the technology dimension with new capabilities on the other dimension thus resulting in niche creation and revolutionary type innovations. Correspondingly, companies with a weaker or more one-sided set of dynamic capabilities seem to produce more radical innovations requiring both new market and technological capabilities. The study therefore provides an empirical contribution to the emerging work on dynamic capabilities through its in-depth investigation of the capabilities of the four case firms, and by mapping the patterns between the firm's portfolio of dynamic capabilities and innovation outcomes.

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Along with the tri-lineage of bone, cartilage and fat, human mesenchymal stem cells (hMSCs) retain neural lineage potential. Multiple factors have been described that influence lineage fate of hMSCs including the extracellular microenvironment or niche. The niche includes the extracellular matrix (ECM) providing structural composition, as well as other associated proteins and growth factors, which collectively influence hMSC stemness and lineage specification. As such, lineage specific differentiation of MSCs is mediated through interactions including cell–cell and cell–matrix, as well as through specific signalling pathways triggering downstream events. Proteoglycans (PGs) are ubiquitous within this microenvironment and can be localised to the cell surface or embedded within the ECM. In addition, the heparan sulfate (HS) and chondroitin sulfate (CS) families of PGs interact directly with a number of growth factors, signalling pathways and ECM components including FGFs, Wnts and fibronectin. With evidence supporting a role for HSPGs and CSPGs in the specification of hMSCs down the osteogenic, chondrogenic and adipogenic lineages, along with the localisation of PGs in development and regeneration, it is conceivable that these important proteins may also play a role in the differentiation of hMSCs toward the neuronal lineage. Here we summarise the current literature and highlight the potential for HSPG directed neural lineage fate specification in hMSCs, which may provide a new model for brain damage repair.