Scalability and process transfer of mesenchymal stromal cell production from monolayer to microcarrier culture using human platelet lysate

Background aims: The selection of medium and associated reagents for human mesenchymal stromal cell (hMSC) culture forms an integral part of manufacturing process development and must be suitable for multiple process scales and expansion technologies. Methods: In this work, we have expanded BM-hMSCs in fetal bovine serum (FBS)- and human platelet lysate (HPL)-containing media in both a monolayer and a suspension-based microcarrier process. Results: The introduction of HPL into the monolayer process increased the BM-hMSC growth rate at the first experimental passage by 0.049 day and 0.127/day for the two BM-hMSC donors compared with the FBS-based monolayer process. This increase in growth rate in HPL-containing medium was associated with an increase in the inter-donor consistency, with an inter-donor range of 0.406 cumulative population doublings after 18 days compared with 2.013 in FBS-containing medium. Identity and quality characteristics of the BM-hMSCs are also comparable between conditions in terms of colony-forming potential, osteogenic potential and expression of key genes during monolayer and post-harvest from microcarrier expansion. BM-hMSCs cultured on microcarriers in HPL-containing medium demonstrated a reduction in the initial lag phase for both BM-hMSC donors and an increased BM-hMSC yield after 6 days of culture to 1.20 ± 0.17 × 105 and 1.02 ± 0.005 × 105 cells/mL compared with 0.79 ± 0.05 × 105 and 0.36 ± 0.04 × 105 cells/mL in FBS-containing medium. Conclusions: This study has demonstrated that HPL, compared with FBS-containing medium, delivers increased growth and comparability across two BM-hMSC donors between monolayer and microcarrier culture, which will have key implications for process transfer during scale-up.

Ozone and climate:scientific consensus and leadership

This article compares the cases of ozone layer protection and climate change. In both cases, scientific expertise has played a comparatively important role in the policy process. The author argues that against conventional assumptions, scientific consensus is not necessary to achieve ambitious political goals. However, the architects of the Intergovernmental Panel on Climate Change operated under such assumptions. The author argues that this is problematic both from a theoretical viewpoint and from empirical evidence. Contrary to conventional assumptions, ambitious political regulations in the ozone case were agreed under scientific uncertainty, whereas the negotiations on climate change were much more modest albeit based on a large scientific consensus. On the basis of a media analysis, the author shows that the creation of a climate of expectation plus pressure from leader countries is crucial for success. © 2006 Sage Publication.

Strategizing:the challenges of a practice perspective

While the strategy-as-practice research agenda has gained considerable momentum over the past five years, many challenges still remain in developing it into a robust field of research. In this editorial, we define the study of strategy from a practice perspective and propose five main questions that the strategy-as-practice agenda seeks to address. We argue that a coherent approach to answering these questions may be facilitated using an overarching conceptual framework of praxis, practices and practitioners. This framework is used to explain the key challenges underlying the strategy-as-practice agenda and how they may be examined empirically. In discussing these challenges, we refer to the contributions made by existing empirical research and highlight under-explored areas that will provide fruitful avenues for future research. The editorial concludes by introducing the articles in the special issue.

Transformational leadership, innovative behavior and task performance:test of mediation and moderation processes

We use the self-concept based theory of leadership and social exchange theory to hypothesize processes linking transformational leadership to follower performance outcomes. Specifically, we hypothesize that (a) transformational leadership relates to followers' work engagement both directly and indirectly through their psychological states, (b) work engagement relates to innovative behavior, (c) innovative behavior relates to task performance, and (d) the work engagement–innovative behavior relationship is moderated by leader–member exchange. Results from a test of these relationships in a sample of employees of a large telecommunication company in China largely support our hypothesized model.

A polymorphism in the growth hormone (GH)-releasing hormone (GHRH) receptor gene is associated with elevated response to GHRH by human pituitary somatotrophinomas in vitro

A previous study has suggested that a G to A base change at position 169 of the GHRH-receptor gene in human somatotrophinomas is a mutation and confers hypersensitivity to GHRH. The alternative base converts codon 57 from GCG to AGC, resulting in replacement of alanine (Ala) with threonine (Thr). In the present study, two of five human GH-secreting somatotrophinomas were found to possess the codon 57 AGC sequence. The GCG allele was also detected, indicating heterozygosity. However, the patients' normal blood-derived DNA also yielded the same sequence pattern, indicating that the Ala=> Thr amino acid change is a normal polymorphism, and not a somatic mutation. Nevertheless, in vitro, the tumors possessing the Ala=> Thr amino acid change responded very strongly to GHRH in terms of cAMP formation, being increased 40- and 200-fold, in comparison to the 2-fold increases by tumors without the alternative GHRH-receptor sequence. Likewise, the in vitro response of GH secretion to GHRH was elevated. One of the two tumors with the alternative Thr residue, and the highest responder to GHRH, possessed a gsp muration, despite the fact that these defects are thought to reduce responsiveness to GHRH. These results fail to confirm that the GCG => AGC at codon 57 of the GHRH-receptor gene is a mutation, but do support the concept that the alternative form with Thr confers increased sensitivity to GHRH. (C) 2000 Academic Press.