Abstract.
This paper focuses on Cap Gemini’s electronic commerce system, TransLease. TransLease is an interorganizational information system (IOS), which facilitates electronic commerce between motor vehicle leasing and repair companies. During our investigation, the system was used by approximately 1000 repair agents working for seven of the UK’s leading vehicle leasing and contract hire companies. This system was originally developed by AT&T and acquired by Cap Gemini in July 1998. At the time of acquisition, the system was seen as being of high strategic value, although it was also seen as underperforming. This paper reports the results of an action research project, which formed one element of the process by which Cap Gemini investigated the former problem. In the paper, TransLease is described as a complex electronic community, dependent upon the existence of symbiotic relationships. As such, the problems that the system users and developers experienced can be attributed to factors that impeded the mutual benefit accruing from participation in the system. The efficacy of the terms of exchange and the degree to which participants mutually benefit through electronic interaction is determined by the complex interplay of a number of relational and organizational factors. The research therefore illustrates the importance of the ‘soft’ organizational issues in IOS management and development, and suggests a conceptual model of the factors relevant in this case. At the time of this study, TransLease was still in the early stages of its life cycle, having only been available in the marketplace for approximately 18 months. During this time, through recognizing the complex problems and issues detailed in this paper, Cap Gemini accordingly redressed the way in which the system was managed and maintained. TransLease is now seen as having matured into a highly successful example of an IOS – a view reflected by its position as market leader in the industry. As this paper will show, the key to improving the existing service has been the emphasis Cap Gemini now places on managing the ‘soft’ aspects of the electronic community.
Islet transplantation is an efficacious therapy for type 1 diabetes; however, islets from multiple donor pancreata are required, and a gradual attrition in transplant function is seen. Here, we manufactured human umbilical cord perivascular mesenchymal stromal cells (HUCPVCs) to Good Manufacturing Practice (GMP) standards. HUCPVCs showed a stable phenotype while undergoing rapid ex vivo expansion at passage 2 (p2) to passage 4 (p4) and produced proregenerative factors, strongly suppressing T cell responses in the resting state and in response to inflammation. Transplanting an islet equivalent (IEQ):HUCPVC ratio of 1:30 under the kidney capsule in diabetic NSG mice demonstrated the fastest return to normoglycemia by 3 days after transplant: Superior glycemic control was seen at both early (2.7 weeks) and later stages (7, 12, and 16 weeks) versus ratios of 1:0, 1:10, and 1:50, respectively. Syngeneic islet transplantation in immunocompetent mice using the clinically relevant hepatic portal route with a marginal islet mass showed that mice transplanted with an IEQ:HUCPVC ratio of 1:150 had superior glycemic control versus ratios of 1:0, 1:90, and 1:210 up to 6 weeks after transplant. Immunodeficient mice transplanted with human islets (IEQ:HUCPVC ratio of 1:150) exhibited better glycemic control for 7 weeks after transplant versus islet transplant alone, and islets transplanted via the hepatic portal vein in an allogeneic mouse model using a curative islet mass demonstrated delayed rejection of islets when cotransplanted with HUCPVCs (IEQ:HUCPVC ratio of 1:150). The immunosuppressive and proregenerative properties of HUCPVCs demonstrated long-term positive effects on graft function in vivo, indicating that they may improve long-term human islet allotransplantation outcomes.
Background aims: Mesenchymal stromal cells (MSCs) isolated from various tissues are under investigation as cellular therapeutics in a wide range of diseases. It is appreciated that the basic biological functions of MSCs vary depending on tissue source. However, in-depth comparative analyses between MSCs isolated from different tissue sources under Good Manufacturing Practice (GMP) conditions are lacking. Human clinical-grade low-purity islet (LPI) fractions are generated as a byproduct of islet isolation for transplantation. MSC isolates were derived from LPI fractions with the aim of performing a systematic, standardized comparative analysis of these cells with clinically relevant bone marrow-derived MSCs (BM MSCs). Methods: MSC isolates were derived from LPI fractions and expanded in platelet lysate-supplemented medium or in commercially available xenogeneic-free medium. Doubling rate, phenotype, differentiation potential, gene expression, protein production and immunomodulatory capacity of LPIs were compared with those of BM MSCs. Results: MSCs can be readily derived in vitro from non-transplanted fractions resulting from islet cell processing (i.e., LPI MSCs). LPI MSCs grow stably in serum-free or platelet lysate-supplemented media and demonstrate in vitro self-renewal, as measured by colony-forming unit assay. LPI MSCs express patterns of chemokines and pro-regenerative factors similar to those of BM MSCs and, importantly, are equally able to attract immune cells in vitro and in vivo and suppress T-cell proliferation in vitro. Additionally, LPI MSCs can be expanded to therapeutically relevant doses at low passage under GMP conditions. Conclusions: LPI MSCs represent an alternative source of GMP MSCs with functions comparable to BM MSCs.
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