Regulation of human stem cell research in Australia

Australia is currently well placed to contribute to the global growth of human stem cell research. However, as the science has progressed, authorities have had to deal with the ongoing challenges of regulating such a fast moving field of scientific endeavour. Australia’s past and current approach to regulating the use of embryos in human embryonic stem cell research provides an insight into how Australia may continue to adapt to future regulatory challenges presented by human stem cell research. In the broader context, a number of issues have been identified that may impact upon the success of future human stem cell research in Australia.

Stem cell technologies : regulation, patents and problems

Human embryonic stem cell research promises to deliver in the future a whole range of therapeutic treatments, but currently governments in different jurisdictions must try to regulate this burgeoning area. Part of the problem has been, and continues to be, polarised community opinion on the use of human embryonic stem cells for research. This article compares the approaches of the Australian, United Kingdom and United States governments in regulating human embryonic stem cell research. To date, these governments have approached the issue through implementing legislation or policy to control research. Similarly, the three jurisdictions have viewed the patentability of human embryonic stem cell technologies in their own ways with different policies being adopted by the three patent offices. This article examines these different approaches and discusses the inevitable concerns that have been raised due to the lack of a universal approach in relation to the regulation of research; the patenting of stem cell technologies; and the effects patents granted are having on further human embryonic stem cell research.

Temporal construal in advertising : the moderating role of temporal orientation and attribute importance in consumer evaluations

In two experiments, we study how the temporal orientation of consumers (i.e., future-oriented or present-oriented), temporal construal (distant future, near future), and product attribute importance (primary, secondary) influence advertisement evaluations. Data suggest that future-oriented consumers react most favorably to ads that feature a product to be released in the distant future and that highlight primary product attributes. In contrast, present-oriented consumers prefer near-future ads that highlight secondary product attributes. Study 2 shows that consumer attitudes are mediated by perceptions of attribute diagnosticity (i.e., the perceived usefulness of the attribute information). Together, these experiments shed light on how individual differences, such as temporal orientation, offer valuable insights into temporal construal effects in advertising.

Stem cell regulatory gene expression in human adult dental pulp and periodontal ligament cells undergoing odontogenic/osteogenic differentiation

Introduction During development and regeneration, odontogenesis and osteogenesis are initiated by a cascade of signals driven by several master regulatory genes. Methods In this study, we investigated the differential expression of 84 stem cell–related genes in dental pulp cells (DPCs) and periodontal ligament cells (PDLCs) undergoing odontogenic/osteogenic differentiation. Results Our results showed that, although there was considerable overlap, certain genes had more differential expression in PDLCs than in DPCs. CCND2, DLL1, and MME were the major upregulated genes in both PDLCs and DPCs, whereas KRT15 was the only gene significantly downregulated in PDLCs and DPCs in both odontogenic and osteogenic differentiation. Interestingly, a large number of regulatory genes in odontogenic and osteogenic differentiation interact or crosstalk via Notch, Wnt, transforming growth factor β (TGF-β)/bone morphogenic protein (BMP), and cadherin signaling pathways, such as the regulation of APC, DLL1, CCND2, BMP2, and CDH1. Using a rat dental pulp and periodontal defect model, the expression and distribution of both BMP2 and CDH1 have been verified for their spatial localization in dental pulp and periodontal tissue regeneration. Conclusions This study has generated an overview of stem cell–related gene expression in DPCs and PDLCs during odontogenic/osteogenic differentiation and revealed that these genes may interact through the Notch, Wnt, TGF-β/BMP, and cadherin signalling pathways to play a crucial role in determining the fate of dental derived cell and dental tissue regeneration. These findings provided a new insight into the molecular mechanisms of the dental tissue mineralization and regeneration

Amniotic fluid stem cells produce robust mineral deposits on biodegradable scaffolds

Insufficient availability of osteogenic cells limits bone regeneration through cell-based therapies. This study investigated the potential of amniotic fluid–derived stem (AFS) cells to synthesize mineralized extracellular matrix within porous medical-grade poly-e-caprolactone (mPCL) scaffolds. The AFS cells were initially differentiated in two-dimensional (2D) culture to determine appropriate osteogenic culture conditions and verify physiologic mineral production by the AFS cells. The AFS cells were then cultured on 3D mPCL scaffolds (6-mm diameter9-mm height) and analyzed for their ability to differentiate to osteoblastic cells in this environment. The amount and distribution of mineralized matrix production was quantified throughout the mPCL scaffold using nondestructive micro computed tomography (microCT) analysis and confirmed through biochemical assays. Sterile microCT scanning provided longitudinal analysis of long-term cultured mPCL constructs to determine the rate and distribution of mineral matrix within the scaffolds. The AFS cells deposited mineralized matrix throughout the mPCL scaffolds and remained viable after 15 weeks of 3D culture. The effect of predifferentiation of the AFS cells on the subsequent bone formation in vivo was determined in a rat subcutaneous model. Cells that were pre-differentiated for 28 days in vitro produced seven times more mineralized matrix when implanted subcutaneously in vivo. This study demonstrated the potential of AFS cells to produce 3D mineralized bioengineered constructs in vitro and in vivo and suggests that AFS cells may be an effective cell source for functional repair of large bone defects

Cellular senescence and longevity of osteophyte-derived mesenchymal stem cells compared to patient-matched bone marrow stromal cells

This study aimed to determine the cellular aging of osteophyte-derived mesenchymal cells (oMSCs) in comparison to patient-matched bone marrow stromal cells (bMSCs). Extensive expansion of the cell cultures was performed and early and late passage cells (passages 4 and 9, respectively) were used to study signs of cellular aging, telomere length, telomerase activity, and cell-cycle-related gene expression. Our results showed that cellular aging was more prominent in bMSCs than in oMSCs, and that oMSCs had longer telomere length in late passages compared with bMSCs, although there was no significant difference in telomere lengths in the early passages in either cell type. Telomerase activity was detectable only in early passage oMSCs and not in bMSCs. In osteophyte tissues telomerase-positive cells were found to be located perivascularly and were Stro-1 positive. Fifteen cell-cycle regulator genes were investigated and only three genes (APC, CCND2, and BMP2) were differentially expressed between bMSC and oMSC. Our results indicate that oMSCs retain a level of telomerase activity in vitro, which may account for the relatively greater longevity of these cells, compared with bMSCs, by preventing replicative senescence. J. Cell. Biochem. 108: 839-850, 2009. (c) 2009 Wiley-Liss, Inc.

A 1H-MRS investigation of the medial temporal lobe in antipsychotic-naïve and early-treated first episode psychosis

Schizophrenia is associated with significant brain abnormalities, including changes in brain metabolites as measured by proton magnetic resonance spectroscopy (MRS). What remains unclear is the extent to which these changes are a consequence of the emergence of psychotic disorders or the result of treatment with antipsychotic medication. We assessed 34 patients with first episode psychosis (15 antipsychotic naïve) and 19 age- and gender-matched controls using short-echo MRS in the medial temporal lobe bilaterally. Overall, there were no differences in any metabolite, regardless of treatment status. However, when the analysis was limited to patients with a diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, significant elevations of creatine/phosphocreatine (Cr/PCr) and myo-inositol (mI) were found in the treated group. These data indicate a relative absence of temporal lobe metabolic abnormalities in first episode psychosis, but suggest that some treatment-related changes in mI might be apparent in patients with schizophrenia-spectrum diagnoses. Seemingly illness-related Cr/PCr elevations were also specific to the diagnosis of schizophrenia-spectrum disorder and seem worthy of future study.

Strategic short termism as an issue of top-teams’ temporal orientation

Short-termism among firms, the tendency to excessively discount long-term benefits and favour less valuable short-term benefits, has been a prominent issue in business and public policy debates but research to date has been inconclusive. We study how managers frame, interpret, and resolve problems of intertemporal choice in actual decisions by using computer aided text analysis to measure the frequency of top-team temporal references in 1653 listed Australian firms between 1992-2005. Contrary to short-termism arguments we find evidence of a significant general increase in Future orientation and a significant decrease in Current/Past orientation. We also show top-teams’ temporal orientation is related to their strategic orientation, specifically the extent to which they focus on Innovation-Expansion and Capacity Building.

Functional outcome of transfemoral amputees fitted with an osseointegrated fixation : temporal gait characteristics

The purpose of this study was to characterise the functional outcome of 12 transfemoral amputees fitted with osseointegrated fixation using temporal gait characteristics. The objectives were (A) to present the cadence, duration of gait cycle, support and swing phases with an emphasis on the stride-to-stride and participant-to-participant variability, and (B) to compare these temporal variables with normative data extracted from the literature focusing on transfemoral amputees fitted with a socket and able-bodied participants. The temporal variables were extracted from the load applied on the residuum during straight level walking, which was collected at 200 Hz by a transducer. A total of 613 strides were assessed. The cadence (46±4 strides/min), the duration of the gait cycle (1.29±0.11 s), support (0.73±0.07 s, 57±3% of CG) and swing (0.56±0.07 s, 43±3% of GC) phases of the participants were 2% quicker, 3%, 6% shorter and 1% longer than transfemoral amputees using a socket as well as 11% slower, 9%, 6% and 13% longer than able-bodied, respectively. All combined, the results indicated that the fitting of an osseointegrated fixation has enabled this group of amputees to restore their locomotion with a highly functional level. Further longitudinal and cross-sectional studies would be required to confirm these outcomes. Nonetheless, the data presented can be used as benchmark for future comparisons. It can also be used as input in generic algorithms using templates of patterns of loading to recognise activities of daily living and to detect falls.