Reimagining the potential of Earth observations for ecosystem service assessments.

The benefits nature provides to people, called ecosystem services, are increasingly recognized and accounted for in assessments of infrastructure development, agricultural management, conservation prioritization, and sustainable sourcing. These assessments are often limited by data, however, a gap with tremendous potential to be filled through Earth observations (EO), which produce a variety of data across spatial and temporal extents and resolutions. Despite widespread recognition of this potential, in practice few ecosystem service studies use EO. Here, we identify challenges and opportunities to using EO in ecosystem service modeling and assessment. Some challenges are technical, related to data awareness, processing, and access. These challenges require systematic investment in model platforms and data management. Other challenges are more conceptual but still systemic; they are byproducts of the structure of existing ecosystem service models and addressing them requires scientific investment in solutions and tools applicable to a wide range of models and approaches. We also highlight new ways in which EO can be leveraged for ecosystem service assessments, identifying promising new areas of research. More widespread use of EO for ecosystem service assessment will only be achieved if all of these types of challenges are addressed. This will require non-traditional funding and partnering opportunities from private and public agencies to promote data exploration, sharing, and archiving. Investing in this integration will be reflected in better and more accurate ecosystem service assessments worldwide.

Effects of human demand on conservation planning for biodiversity and ecosystem services.

Safeguarding ecosystem services and biodiversity is critical to achieving sustainable development. To date, ecosystem services quantification has focused on the biophysical supply of services with less emphasis on human beneficiaries (i.e., demand). Only when both occur do ecosystems benefit people, but demand may shift ecosystem service priorities toward human-dominated landscapes that support less biodiversity. We quantified how accounting for demand affects the efficiency of conservation in capturing both human benefits and biodiversity by comparing conservation priorities identified with and without accounting for demand. We mapped supply and benefit for 3 ecosystem services (flood mitigation, crop pollination, and nature-based recreation) by adapting existing ecosystem service models to include and exclude factors representing human demand. We then identified conservation priorities for each with the conservation planning program Marxan. Particularly for flood mitigation and crop pollination, supply served as a poor proxy for benefit because demand changed the spatial distribution of ecosystem service provision. Including demand when jointly targeting biodiversity and ecosystem service increased the efficiency of conservation efforts targeting ecosystem services without reducing biodiversity outcomes. Our results highlight the importance of incorporating demand when quantifying ecosystem services for conservation planning.

Efectos de la Demanda Humana sobre la Planeación de la Conservación para la Biodiversidad y los Servicios Ambientales Resumen La salvaguardia de los servicios ambientales y de la biodiversidad es muy importante para lograr el desarrollo sustentable. A la fecha, la cuantificación de los servicios ambientales se ha enfocado en el suministro biofísico de servicios con un menor énfasis en los beneficiarios humanos (es decir, la demanda). Es sólo cuando se considera a ambos que los ecosistemas benefician a las personas, pero la demanda puede cambiar las prioridades de los servicios ambientales hacia los paisajes dominados por humanos, los cuales mantienen una menor biodiversidad. Cuantificamos cómo afecta la consideración de la demanda a la eficiencia de la conservación en la captura de los beneficios humanos y de la biodiversidad al comparar las prioridades de conservación con y sin la consideración de la demanda. Mapeamos el suministro y el beneficio para tres servicios ambientales (mitigación de inundaciones, polinización de cultivos y actividades recreativas basadas en la naturaleza) al adaptar los modelos de servicios ambientales existentes para que incluyeran y excluyeran los factores que representan la demanda humana. Después identificamos las prioridades de conservación para cada uno con el programa de planeación de la conservación Marxan. En el caso particular de la mitigación de inundaciones y la polinización de cultivos, el suministro fue un sustituto pobre para el beneficio debido a que la demanda cambió la distribución espacial de la provisión de servicios ambientales. La inclusión de la demanda cuando nos enfocamos en la biodiversidad y en los servicios ambientales como conjunto incrementó la eficiencia de los esfuerzos de conservación enfocados en los servicios ambientales sin reducir los resultados para la biodiversidad. Nuestros resultados resaltan la importancia de la incorporación de la demanda cuando se cuantifican los servicios ambientales para la planeación de la conservación.

Disaggregating the evidence linking biodiversity and ecosystem services.

Ecosystem services (ES) are an increasingly popular policy framework for connecting biodiversity with human well-being. These efforts typically assume that biodiversity and ES covary, but the relationship between them remains remarkably unclear. Here we analyse >500 recent papers and show that reported relationships differ among ES, methods of measuring biodiversity and ES, and three different approaches to linking them (spatial correlations, management comparisons and functional experiments). For spatial correlations, biodiversity relates more strongly to measures of ES supply than to resulting human benefits. For management comparisons, biodiversity of 'service providers' predicts ES more often than biodiversity of functionally unrelated taxa, but the opposite is true for spatial correlations. Functional experiments occur at smaller spatial scales than management and spatial studies, which show contrasting responses to scale. Our results illuminate the varying dynamics relating biodiversity to ES, and show the importance of matching management efforts to the most relevant scientific evidence.

Spatial and Temporal Dynamics and Value of Nature-Based Recreation, Estimated via Social Media.

Conserved lands provide multiple ecosystem services, including opportunities for nature-based recreation. Managing this service requires understanding the landscape attributes underpinning its provision, and how changes in land management affect its contribution to human wellbeing over time. However, evidence from both spatially explicit and temporally dynamic analyses is scarce, often due to data limitations. In this study, we investigated nature-based recreation within conserved lands in Vermont, USA. We used geotagged photographs uploaded to the photo-sharing website Flickr to quantify visits by in-state and out-of-state visitors, and we multiplied visits by mean trip expenditures to show that conserved lands contributed US $1.8 billion (US $0.18-20.2 at 95% confidence) to Vermont's tourism industry between 2007 and 2014. We found eight landscape attributes explained the pattern of visits to conserved lands; visits were higher in larger conserved lands, with less forest cover, greater trail density and more opportunities for snow sports. Some of these attributes differed from those found in other locations, but all aligned with our understanding of recreation in Vermont. We also found that using temporally static models to inform conservation decisions may have perverse outcomes for nature-based recreation. For example, static models suggest conserved land with less forest cover receive more visits, but temporally dynamic models suggest clearing forests decreases, rather than increases, visits to these sites. Our results illustrate the importance of understanding both the spatial and temporal dynamics of ecosystem services for conservation decision-making.

Origins of the tumor microenvironment: quantitative assessment of adipose-derived and bone marrow-derived stroma.

To meet the requirements for rapid tumor growth, a complex array of non-neoplastic cells are recruited to the tumor microenvironment. These cells facilitate tumor development by providing matrices, cytokines, growth factors, as well as vascular networks for nutrient and waste exchange, however their precise origins remain unclear. Through multicolored tissue transplant procedures; we have quantitatively determined the contribution of bone marrow-derived and adipose-derived cells to stromal populations within syngeneic ovarian and breast murine tumors. Our results indicate that subpopulations of tumor-associated fibroblasts (TAFs) are recruited from two distinct sources. The majority of fibroblast specific protein (FSP) positive and fibroblast activation protein (FAP) positive TAFs originate from mesenchymal stem/stromal cells (MSC) located in bone marrow sources, whereas most vascular and fibrovascular stroma (pericytes, α-SMA(+) myofibroblasts, and endothelial cells) originates from neighboring adipose tissue. These results highlight the capacity for tumors to utilize multiple sources of structural cells in a systematic and discriminative manner.

Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment.

BACKGROUND AIMS: Because of the inflammatory nature and extensive stromal compartment in pancreatic tumors, we investigated the role of mesenchymal stromal cells (MSC) to engraft selectively in pancreatic carcinomas and serve as anti-tumor drug delivery vehicles to control pancreatic cancer progression. METHODS: Human pancreatic carcinoma cells, PANC-1, expressing renilla luciferase were orthotopically implanted into SCID mice and allowed to develop for 10 days. Firefly luciferase-transduced MSC or MSC expressing interferon (IFN)-beta were then injected intraperitoneally weekly for 3 weeks. Mice were monitored by bioluminescent imaging for expression of renilla (PANC-1) and firefly (MSC) luciferase. RESULTS: MSC selectively homed to sites of primary and metastatic pancreatic tumors and inhibited tumor growth (P=0.032). The production of IFN-beta within the tumor site by MSC-IFN-beta further suppressed tumor growth (P=0.0000083). Prior studies indicated that MSC home to sites of inflammation; therefore, we sought to alter the tumor microenvironment through treatment with a potent anti-inflammatory agent. After treatment, inflammation-associated mediators were effectively down-regulated, including NFkappaB, vascular endothelial growth factor (VEGF) and interleukin (IL)-6 as well as chemokines involved in MSC migration (CCL3 and CCL25). Treatment with the anti-inflammatory agent CDDO-Me before and after MSC-IFN-beta injections resulted in reduction of MSC in the tumors and reversed the positive effect of tumor inhibition by MSC-IFN-beta alone (P=0.041). CONCLUSIONS: These results suggest that MSC exhibit innate anti-tumor effects against PANC-1 cells and can serve as delivery vehicles for IFN-beta for the treatment of pancreatic cancer. However, these beneficial effects may be lost in therapies combining MSC with anti-inflammatory agents.

Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging.

Multipotent mesenchymal stromal/stem cells (MSC) have shown potential clinical utility. However, previous assessments of MSC behavior in recipients have relied on visual detection in host tissue following sacrifice, failing to monitor in vivo MSC dispersion in a single animal and limiting the number of variables that can be observed concurrently. In this study, we used noninvasive, in vivo bioluminescent imaging to determine conditions under which MSC selectively engraft in sites of inflammation. MSC modified to express firefly luciferase (ffLuc-MSC) were injected into healthy mice or mice bearing inflammatory insults, and MSC localization was followed with bioluminescent imaging. The inflammatory insults investigated included cutaneous needle-stick and surgical incision wounds, as well as xenogeneic and syngeneic tumors. We also compared tumor models in which MSC were i.v. or i.p. delivered. Our results demonstrate that ffLuc-expressing human MSC (hMSC) systemically delivered to nontumor-bearing animals initially reside in the lungs, then egress to the liver and spleen, and decrease in signal over time. However, hMSC in wounded mice engraft and remain detectable only at injured sites. Similarly, in syngeneic and xenogeneic breast carcinoma-bearing mice, bioluminescent detection of systemically delivered MSC revealed persistent, specific colocalization with sites of tumor development. This pattern of tropism was also observed in an ovarian tumor model in which MSC were i.p. injected. In this study, we identified conditions under which MSC tropism and selective engraftment in sites of inflammation can be monitored by bioluminescent imaging over time. Importantly, these consistent findings were independent of tumor type, immunocompetence, and route of MSC delivery.

Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression.

BACKGROUND: Tumor associated fibroblasts (TAF), are essential for tumor progression providing both a functional and structural supportive environment. TAF, known as activated fibroblasts, have an established biological impact on tumorigenesis as matrix synthesizing or matrix degrading cells, contractile cells, and even blood vessel associated cells. The production of growth factors, cytokines, chemokines, matrix-degrading enzymes, and immunomodulatory mechanisms by these cells augment tumor progression by providing a suitable environment. There are several suggested origins of the TAF including tissue-resident, circulating, and epithelial-to-mesenchymal-transitioned cells. METHODOLOGY/PRINCIPAL FINDINGS: We provide evidence that TAF are derived from mesenchymal stem cells (MSC) that acquire a TAF phenotype following exposure to or systemic recruitment into adenocarcinoma xenograft models including breast, pancreatic, and ovarian. We define the MSC derived TAF in a xenograft ovarian carcinoma model by the immunohistochemical presence of 1) fibroblast specific protein and fibroblast activated protein; 2) markers phenotypically associated with aggressiveness, including tenascin-c, thrombospondin-1, and stromelysin-1; 3) production of pro-tumorigenic growth factors including hepatocyte growth factor, epidermal growth factor, and interleukin-6; and 4) factors indicative of vascularization, including alpha-smooth muscle actin, desmin, and vascular endothelial growth factor. We demonstrate that under long-term tumor conditioning in vitro, MSC express TAF-like proteins. Additionally, human MSC but not murine MSC stimulated tumor growth primarily through the paracrine production of secreted IL6. CONCLUSIONS/SIGNIFICANCE: Our results suggest the dependence of in vitro Skov-3 tumor cell proliferation is due to the presence of tumor-stimulated MSC secreted IL6. The subsequent TAF phenotype arises from the MSC which ultimately promotes tumor growth through the contribution of microvascularization, stromal networks, and the production of tumor-stimulating paracrine factors.

The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells.

Bone marrow-derived mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) have been shown to engraft into the stroma of several tumor types, where they contribute to tumor progression and metastasis. However, the chemotactic signals mediating MSC migration to tumors remain poorly understood. Previous studies have shown that LL-37 (leucine, leucine-37), the C-terminal peptide of human cationic antimicrobial protein 18, stimulates the migration of various cell types and is overexpressed in ovarian, breast, and lung cancers. Although there is evidence to support a pro-tumorigenic role for LL-37, the function of the peptide in tumors remains unclear. Here, we demonstrate that neutralization of LL-37 in vivo significantly reduces the engraftment of MSCs into ovarian tumor xenografts, resulting in inhibition of tumor growth as well as disruption of the fibrovascular network. Migration and invasion experiments conducted in vitro indicated that the LL-37-mediated migration of MSCs to tumors likely occurs through formyl peptide receptor like-1. To assess the response of MSCs to the LL-37-rich tumor microenvironment, conditioned medium from LL-37-treated MSCs was assessed and found to contain increased levels of several cytokines and pro-angiogenic factors compared with controls, including IL-1 receptor antagonist, IL-6, IL-10, CCL5, VEGF, and matrix metalloproteinase-2. Similarly, Matrigel mixed with LL-37, MSCs, or the combination of the two resulted in a significant number of vascular channels in nude mice. These data indicate that LL-37 facilitates ovarian tumor progression through recruitment of progenitor cell populations to serve as pro-angiogenic factor-expressing tumor stromal cells.