Human embryonic and mesenchymal stem cell therapies may offer significant benefit to a large number of patients. Recently, however, human embryonic stem cell lines cultured on mouse feeder cells were reported to be contaminated by the xeno-carbohydrate N-glycolylneuraminic acid (Neu5Gc) and considered potentially unfit for human therapy. To determine the extent of the problem of Neu5Gc contamination for the development of stem cell therapies, we investigated whether it also occurs in cells cultured on human feeder cells and in mesenchymal stem cells, what are the sources of contamination, and whether the contamination is reversible. We found that N-glycolylneuraminic acid was present in embryonic stem cells cultured on human feeder cells, correlating with the presence of Neu5Gc in components of the commercial serum replacement culture medium. Similar contamination occurred in mesenchymal stem cells cultured in the presence of fetal bovine serum. The results suggest that the Neu5Gc is present in both glycoprotein and lipid-linked glycans, as detected by mass spectrometric analysis and monoclonal antibody staining, respectively. Significantly, the contamination was largely reversible in the progeny of both cell types, suggesting that decontaminated cells may be derived from existing stem cell lines. Although major complications have not been reported in the clinical trials with mesenchymal stem cells exposed to fetal bovine serum, the immunogenic contamination may potentially be reflected in the viability and efficacy of the transplanted cells and thus bias the published results. Definition of safe culture conditions for stem cells is essential for future development of cellular therapies. STEM CELLS 2007;25: 197-202

Surrogate concepts are used in all sub-disciplines of environmental science. However, controversy remains regarding the extent to which surrogates are useful for resolving environmental problems. Here, we argue that conflicts about the utility of surrogates (and the related concepts of indicators and proxies) often reflect context-specific differences in trade-offs between measurement accuracy and practical constraints. By examining different approaches for selecting and applying surrogates, we identify five trade-offs that correspond to key points of contention in the application of surrogates. We then present an 8-step Adaptive Surrogacy Framework that incorporates cross-disciplinary perspectives from a wide spectrum of the environmental sciences, aiming to unify surrogate concepts across disciplines and applications. Our synthesis of the science of surrogates is intended as a first step towards fully leveraging knowledge accumulated across disciplines, thus consolidating lessons learned so that they may be accessible to all those operating in different fields, yet facing similar hurdles.

Human mesenchymal stem cells (MSCs) are adult multipotent progenitor cells. They hold an enormous therapeutic potential, but at the moment there is little information on the properties of MSCs, including their surface structures. In the present study, we analyzed the mesenchymal stem cell glycome by using mass spectrometric profiling as well as a panel of glycan binding proteins. Structural verifications were obtained by nuclear magnetic resonance spectroscopy, mass spectrometric fragmentation, and glycosidase digestions. The MSC glycome was compared to the glycome of corresponding osteogenically differentiated cells. More than one hundred glycan signals were detected in mesenchymal stem cells and osteoblasts differentiated from them. The glycan profiles of MSCs and osteoblasts were consistently different in biological replicates, indicating that stem cells and osteoblasts have characteristic glycosylation features. Glycosylation features associated with MSCs rather than differentiated cells included high-mannose type N-glycans, linear poly-N-acetyllactosamine chains and α2-3-sialylation.

The current sustainability challenges and the required systemic transformation highlight the need for innovations on multiple levels. Ecodesign integrates environmental aspects into product and process design to reduce environmental impacts, whereas eco‐innovation also concerns nontechnological solutions. In this paper, we formulate a model that combines eco‐innovation targets ad mechanisms with sustainability maturity, which also concerns stimuli and barriers faced by companies and ecodesign tools used. The results are based on a questionnaire sent to 902 textile and information technology (IT) companies (N = 104) in the Nordic countries. The tools that Nordic textile and IT companies use in particular are life cycle assessment, type I ecolabel, and carbon footprint. Internal stimuli, especially general willingness, were important for eco‐innovativeness, while legislation and customer demand also pushed companies forward. Specific no‐go barriers were not identified, although increase in costs was a common barrier. The respondents focus often on technological product innovations, but rarely on functional innovation, renting of products, and so forth. This highlights the need to address the availability of the right kind of tools to support a broader suite of innovation that can drive toward the circular economy.

The expression of the epitopes recognized by the monoclonal antibodies Tra-1-60 and Tra-1-81 is routinely used to assess the pluripotency status of human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells. Although it is known that the epitopes recognized by Tra-1-60 and Tra-1-81 are carbohydrates, the exact molecular identity of these epitopes has been unclear. Glycan array analysis with more than 500 oligosaccharide structures revealed specific binding of Tra-1-60 and Tra-1-81 to two molecules containing terminal type 1 lactosamine: Galβ1-3GlcNAcβ1-3Galβ1-4GlcNAc and Galβ1-3GlcNAcβ1-3Galβ1-4GlcNAcβ1-6(Galβ1-3GlcNAcβ1-3)Galβ1-4Glc. The type 1 disaccharide in itself was not sufficient for binding, indicating that the complete epitope requires an extended tetrasaccharide structure where the type 1 disaccharide is β1,3-linked to type 2 lactosamine. Our mass spectrometric analysis complemented with glycosidase digestions of hESC O-glycans indicated the presence of the extended tetrasaccharide epitope on an O-glycan with the likely structure Galβ1-3GlcNAcβ1-3Galβ1-4GlcNAcβ1-6(Galβ1-3)GalNAc. Thus, the present data indicate that the pluripotency marker antibodies Tra-1-60 and Tra-1-81 recognize the minimal epitope Galβ1-3GlcNAcβ1-3Galβ1-4GlcNAc, which is present in hESCs as a part of a mucin-type O-glycan structure. The exact molecular identity of Tra-1-60 and Tra-1-81 is important for the development of improved tools to characterize the pluripotent phenotype.

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Ecological surrogacy-here defined as using a process or element (e.g., species, ecosystem, or abiotic factor) to represent another aspect of an ecological system-is a widely used concept, but many applications of the surrogate concept have been controversial. We argue that some of this controversy reflects differences among users with different goals, a distinction that can be crystalized by recognizing two basic types of surrogate. First, many ecologists and natural resource managers measure "indicator surrogates" to provide information about ecological systems. Second, and often overlooked, are "management surrogates" (e.g., umbrella species) that are primarily used to facilitate achieving management goals, especially broad goals such as "maintain biodiversity" or "increase ecosystem resilience." We propose that 47 distinguishing these two overarching roles for surrogacy may facilitate better communication about project goals. This is critical when evaluating the usefulness of different surrogates, especially where a potential surrogate might be useful in one role but not another. Our classification for ecological surrogacy applies to species, ecosystems, ecological processes, abiotic factors, and genetics, and thus can provide coherence across a broad range of uses.

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