Bone marrow‐derived mesenchymal stem cells (MSCs) hold great promise for treating immune disorders because of their immunoregulatory capacity, but the mechanism remains controversial. As we show here, the mechanism of MSC‐mediated immunosuppression varies among different species. Immunosuppression by human‐ or monkey‐derived MSCs is mediated by indoleamine 2,3‐dioxygenase (IDO), whereas mouse MSCs utilize nitric oxide, under the same culture conditions. When the expression of IDO and inducible nitric oxide synthase (iNOS) were examined in human and mouse MSCs after stimulation with their respective inflammatory cytokines, we found that human MSCs expressed extremely high levels of IDO, and very low levels of iNOS, whereas mouse MSCs expressed abundant iNOS and very little IDO. Immunosuppression by human MSCs was not intrinsic, but was induced by inflammatory cytokines and was chemokine‐dependent, as it is in mouse. These findings provide critical information about the immunosuppression of MSCs and for better application of MSCs in treating immune disorders. STEM CELLS 2009;27:1954–1962

Species Variation in the Mechanisms of Mesenchymal Stem Cell-Mediated Immunosuppression

Global food demand is rising, and serious questions remain about whether supply can increase sustainably1 Land-based expansion is possible but may exacerbate climate change and biodiversity loss, and compromise the delivery of other ecosystem services2–6 As food from the sea represents only 17% of the current production of edible meat, we ask how much food we can expect the ocean to sustainably produce by 2050 Here we examine the main food-producing sectors in the ocean—wild fisheries, finfish mariculture and bivalve mariculture—to estimate ‘sustainable supply curves’ that account for ecological, economic, regulatory and technological constraints We overlay these supply curves with demand scenarios to estimate future seafood production We find that under our estimated demand shifts and supply scenarios (which account for policy reform and technology improvements), edible food from the sea could increase by 21–44 million tonnes by 2050, a 36–74% increase compared to current yields This represents 12–25% of the estimated increase in all meat needed to feed 98 billion people by 2050 Increases in all three sectors are likely, but are most pronounced for mariculture Whether these production potentials are realized sustainably will depend on factors such as policy reforms, technological innovation and the extent of future shifts in demand Modelled supply curves show that, with policy reform and technological innovation, the production of food from the sea may increase sustainably, perhaps supplying 25% of the increase in demand for meat products by 2050

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The future of food from the sea.

Historically, human uses of land have transformed and fragmented ecosystems1,2, degraded biodiversity3,4, disrupted carbon and nitrogen cycles5,6 and added prodigious quantities of greenhouse gases (GHGs) to the atmosphere7,8. However, in contrast to fossil-fuel carbon dioxide (CO2) emissions, trends and drivers of GHG emissions from land management and land-use change (together referred to as ‘land-use emissions’) have not been as comprehensively and systematically assessed. Here we present country-, process-, GHG- and product-specific inventories of global land-use emissions from 1961 to 2017, we decompose key demographic, economic and technical drivers of emissions and we assess the uncertainties and the sensitivity of results to different accounting assumptions. Despite steady increases in population (+144 per cent) and agricultural production per capita (+58 per cent), as well as smaller increases in emissions per land area used (+8 per cent), decreases in land required per unit of agricultural production (–70 per cent) kept global annual land-use emissions relatively constant at about 11 gigatonnes CO2-equivalent until 2001. After 2001, driven by rising emissions per land area, emissions increased by 2.4 gigatonnes CO2-equivalent per decade to 14.6 gigatonnes CO2-equivalent in 2017 (about 25 per cent of total anthropogenic GHG emissions). Although emissions intensity decreased in all regions, large differences across regions persist over time. The three highest-emitting regions (Latin America, Southeast Asia and sub-Saharan Africa) dominate global emissions growth from 1961 to 2017, driven by rapid and extensive growth of agricultural production and related land-use change. In addition, disproportionate emissions are related to certain products: beef and a few other red meats supply only 1 per cent of calories worldwide, but account for 25 per cent of all land-use emissions. Even where land-use change emissions are negligible or negative, total per capita CO2-equivalent land-use emissions remain near 0.5 tonnes per capita, suggesting the current frontier of mitigation efforts. Our results are consistent with existing knowledge—for example, on the role of population and economic growth and dietary choice—but provide additional insight into regional and sectoral trends. Trends in the rate of region- and sector-specific land-use greenhouse gas emissions in 1961–2017 show an acceleration of about 20% per decade after 2001.

Global and regional drivers of land-use emissions in 1961–2017

Mitigating the carbon footprint and improving productivity of ruminant livestock agriculture using a red seaweed

Blue Growth Potential to Mitigate Climate Change through Seaweed Offsetting.

Recent studies using batch-fermentation suggest that the red macroalgae Asparagopsis taxiformis has the potential to reduce methane (CH4) production from beef cattle by up to ~ 99% when added to Rhodes grass hay; a common feed in the Australian beef industry. These experiments have shown significant reductions in CH4 without compromising other fermentation parameters (i.e. volatile fatty acid production) with A. taxiformis organic matter (OM) inclusion rates of up to 5%. In the study presented here, A. taxiformis was evaluated for its ability to reduce methane production from dairy cattle fed a mixed ration widely utilized in California, the largest milk producing state in the US. Fermentation in a semi-continuous in-vitro rumen system suggests that A. taxiformis can reduce methane production from enteric fermentation in dairy cattle by 95% when added at a 5% OM inclusion rate without any obvious negative impacts on volatile fatty acid production. High-throughput 16S ribosomal RNA (rRNA) gene amplicon sequencing showed that seaweed amendment effects rumen microbiome consistent with the Anna Karenina hypothesis, with increased β-diversity, over time scales of approximately 3 days. The relative abundance of methanogens in the fermentation vessels amended with A. taxiformis decreased significantly compared to control vessels, but this reduction in methanogen abundance was only significant when averaged over the course of the experiment. Alternatively, significant reductions of CH4 in the A. taxiformis amended vessels was measured in the early stages of the experiment. This suggests that A. taxiformis has an immediate effect on the metabolic functionality of rumen methanogens whereas its impact on microbiome assemblage, specifically methanogen abundance, is delayed. The methane reducing effect of A. taxiformis during rumen fermentation makes this macroalgae a promising candidate as a biotic methane mitigation strategy for dairy cattle. But its effect in-vivo (i.e. in dairy cattle) remains to be investigated in animal trials. Furthermore, to obtain a holistic understanding of the biochemistry responsible for the significant reduction of methane, gene expression profiles of the rumen microbiome and the host animal are warranted.

/pdf/effect-of-the-macroalgae-asparagopsis-taxiformis-on-methane-45m7f141b2.pdf

Effect of the macroalgae Asparagopsis taxiformis on methane production and rumen microbiome assemblage

Adipose-derived mesenchymal stem cells (ASCs) are a promising cell therapy to treat inflammatory and immune-mediated diseases. Development of appropriate pre-clinical animal models is critical to determine safety and attain early efficacy data for the most promising therapeutic candidates. Naturally occurring diseases in cats already serve as valuable models to inform human clinical trials in oncologic, cardiovascular, and genetic diseases. The objective of this study was to complete a comprehensive side-by-side comparison of human and feline ASCs, with an emphasis on their immunomodulatory capacity and transcriptome. Human and feline ASCs were evaluated for phenotype, immunomodulatory profile, and transcriptome. Additionally, transwells were used to determine the role of cell-cell contact in ASC-mediated inhibition of lymphocyte proliferation in both humans and cats. Similar to human ASCs, feline ASCs were highly proliferative at low passages and fit the minimal criteria of multipotent stem cells including a compatible surface protein phenotype, osteogenic capacity, and normal karyotype. Like ASCs from all species, feline ASCs inhibited mitogen-activated lymphocyte proliferation in vitro, with or without direct ASC-lymphocyte contact. Feline ASCs mimic human ASCs in their mediator secretion pattern, including prostaglandin E2, indoleamine 2,3 dioxygenase, transforming growth factor beta, and interleukin-6, all augmented by interferon gamma secretion by lymphocytes. The transcriptome of three unactivated feline ASC lines were highly similar. Functional analysis of the most highly expressed genes highlighted processes including: 1) the regulation of apoptosis; 2) cell adhesion; 3) response to oxidative stress; and 4) regulation of cell differentiation. Finally, feline ASCs had a similar gene expression profile to noninduced human ASCs. Findings suggest that feline ASCs modulate lymphocyte proliferation using soluble mediators that mirror the human ASC secretion pattern. Uninduced feline ASCs have similar gene expression profiles to uninduced human ASCs, as revealed by transcriptome analysis. These data will help inform clinical trials using cats with naturally occurring diseases as surrogate models for human clinical trials in the regenerative medicine arena.

/pdf/human-and-feline-adipose-derived-mesenchymal-stem-cells-have-46ufhsw8mi.pdf

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome.

/pdf/correction-to-effect-of-the-macroalgae-asparagopsis-bg3b6kwqdz.pdf

Correction to: Effect of the macroalgae Asparagopsis taxiformis on methane production and rumen microbiome assemblage

Background Recent studies using batch-fermentation suggest that the red macroalgae Asparagopsis taxiformis might reduce methane (CH4) emission from beef cattle by up to ∼99% when added to rhodes grass hay, a common feed in the Australian beef industry. These experiments have shown significant reductions in methane without compromising other fermentation parameters (i.e. volatile fatty acid production) with A. taxiformis organic matter (OM) inclusion rates of up to 5%. In the study presented here, A. taxiformis was evaluated for its ability to reduce methane production from dairy cattle fed a mixed ration widely utilized in California; the largest milk producer in the US. Results Fermentation in a semi-continuous in-vitro rumen system suggests that A. taxiformis can reduce methane production from enteric fermentation in dairy cattle by 95% when added at a 5% OM inclusion rate without any obvious negative impacts on volatile fatty acid production. High-throughput 16S ribosomal RNA (rRNA) gene amplicon sequencing showed that seaweed amendment effects rumen microbiome communities consistent with the Anna Karenina hypothesis, with increased beta-diversity, over time scales of approximately three days. The relative abundance of methanogens in the fermentation vessels amended with A. taxiformis decreased significantly compared to control vessels, but this reduction in methanogen abundance was only significant when averaged over the course of the experiment. Alternatively, significant reductions of methane in the A. taxiformis amended vessels was measured in the early stages of the experiment. This suggests that A. taxiformis has an immediate effect on the metabolic functionality of rumen methanogens whereas its impact on microbiome assemblage, specifically methanogen abundance, is delayed. Conclusions The methane reducing effect of A. taxiformis during rumen fermentation makes this macroalgae a promising candidate as a biotic methane mitigation strategy in the largest milk producing state in the US. But its effect in-vivo (i.e. in dairy cattle) remains to be investigated in animal trials. Furthermore, to obtain a holistic understanding of the biochemistry responsible for the significant reduction of methane, gene expression profiles of the rumen microbiome and the host animal are warranted.

/pdf/effect-of-the-macroalgae-asparagopsis-taxiformis-on-methane-1lddhhul33.pdf

Lyndsey Jean Marsh

Papers

Effect of the macroalgae Asparagopsis taxiformis on methane production and rumen microbiome assemblage

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome.

Correction to: Effect of the macroalgae Asparagopsis taxiformis on methane production and rumen microbiome assemblage

Effect of the macroalgae Asparagopsis taxiformis on methane production and the rumen microbiome assemblage