Dario Furlani

HMGB-1 induces c-kit+ cell microvascular rolling and adhesion via both toll-like receptor-2 and toll-like receptor-4 of endothelial cells.

High‐mobility group box 1 (HMGB‐1) is a strong chemo‐attractive signal for both inflammatory and stem cells. The aim of this study is to evaluate the mechanisms regulating HMGB‐1–mediated adhesion and rolling of c‐kit+ cells and assess whether toll‐like receptor‐2 (TLR‐2) and toll‐like receptor‐4 (TLR‐4) of endothelial cells or c‐kit+ cells are implicated in the activation of downstream migration signals to peripheral c‐kit+ cells. Effects of HMGB‐1 on the c‐kit+ cells/endothelial interaction were evaluated by a cremaster muscle model in wild‐type (WT), TLR‐2 (−/−) and Tlr4 (LPS‐del) mice. The mRNA and protein expression levels of endothelial nitric oxide synthase were determined by quantitative real‐time PCR and immunofluorescence staining. Induction of crucial adhesion molecules for rolling and adhesion of stem cells and leukocytes were monitored in vivo and in vitro. Following local HMGB‐1 administration, a significant increase in cell rolling was detected (32.4 ± 7.1% in ‘WT’ versus 9.9 ± 3.2% in ‘control’, P < 0.05). The number of firmly adherent c‐kit+ cells was more than 13‐fold higher than that of the control group (14.6 ± 5.1 cells/mm2 in ‘WT’ versus 1.1 ± 1.0 cells/mm2 in ‘control’, P < 0.05). In knockout animals, the fraction of rolling cells did not differ significantly from control levels. Firm endothelial adhesion was significantly reduced in TLR‐2 (−/−) and Tlr4 (LPS‐del) mice compared to WT mice (1.5 ± 1.4 cells/mm2 in ‘TLR‐2 (−/−)’ and 2.4 ± 1.4 cells/mm2 in ‘Tlr4 (LPS‐del)’ versus 14.6 ± 5.1 cells/mm2 in ‘WT’, P < 0.05). TLR‐2 (−/−) and Tlr4 (LPS‐del) stem cells in WT mice did not show significant reduction in rolling and adhesion compared to WT cells. HMGB‐1 mediates c‐kit+ cell recruitment via endothelial TLR‐2 and TLR‐4.

Mesenchymal stem cells restore lung function by recruiting resident and nonresident proteins.

Because human lungs are unlikely to repair or regenerate beyond the cellular level, cell therapy has not previously been considered for chronic irreversible obstructive lung diseases. To explore whether cell therapy can restore lung function, we administered allogenic intratracheal mesenchymal stem cells (MSCs) in the trachea of rats with chronic thromboembolic pulmonary hypertension (CTEPH), a disease characterized by single or recurrent pulmonary thromboembolic obliteration and progressive pulmonary vascular remodeling. MSCs were retrieved only in high pressure-exposed lungs recruited via a homing stromal derived factor-1α/ CXCR4 pathway. After MSC administration, a marked and long-lasting improvement of all clinical parameters and a significant change of the proteome level were detected. Beside a variation of liver proteome, such as caspase-3, NF-κB, collagen1A1, and α-SMA, we also identified more than 300 resident and nonresident lung proteins [e.g., myosin light chain 3 (P16409) or mitochondrial ATP synthase subunit alpha (P15999)]. These results suggest that cell therapy restores lung function and the therapeutic effects of MSCs may be related to protein-based tissue reconstituting effects.

Deforestation and the Structure of Frog Communities in the Humedale Terraba-Sierpe, Costa Rica

Loss of tropical forests is a major cause of biodiversity loss worldwide. Although drastic modification of the habitat has been shown to negatively affect amphibians, we are far from a complete understanding of the response of amphibian communities to deforestation. We studied frog assemblages in a gradient of forest modification in a humid area of Costa Rica, where the primary forest has been partially converted into pasture. The study area is a mosaic of primary palm forest, abandoned pasture covered by secondary forest, and pasture. Species richness was assessed by randomized walk surveys and audio strip transects. We also measured ecological features to evaluate the relationship between landscape alteration and amphibian distribution. The study area hosted a large number of amphibian species. We focused our monitoring on six anurans: Leptodactylus labialis, Eleutherodactylus fitzingeri, E. diastema, Hyla rosenbergi, H. microcephala, and Cochranella granulosa. Three species (L. labialis, H. rosenbergi, and H. microcephala) were most abundant in pasture areas with livestock presence, while E. fitzingeri, E. diastema, and C. granulosa were associated with primary forest. Most of the variation in community structure was explained by the joint effect of forest alteration and presence of livestock. Whereas forest specialists suffer direct negative effect from deforestation, generalist species can take advantage of forest alteration and the presence of farm animals. Species that are able to take advantage of the new environmental characteristics associated with human modifications of landscapes will come to prevail in the new communities.

Assessing the value of secondary forest for amphibians: Eleutherodactylus frogs in a gradient of forest alteration

Secondary forests constitute a growing portion of forested areas worldwide. They might have a substantial role for the conservation of biodiversity in tropical areas, but there is little information on their potential to support forest species and the recovery of faunal communities. We studied two forest frogs (Eleutherodactylus diastema and E. fitzingeri) in an area of Costa Rica composed of a mosaic of primary forest, young secondary forest and pasture, and we compared the density of calling males in areas with different forest alteration. Autoregressive models were used to compensate for potentially undesired effects of spatial autocorrelation and pseudoreplication. Both species were most abundant in riparian, primary forest. However, E. fitzingeri was also abundant in riparian secondary forests, and its density far from the river was similar in primary and secondary forest, suggesting that river proximity can influence the recovery of secondary forest for amphibians. Conversely, the density of E. diastema was similar in secondary forest and pasture, stressing interspecific differences for recovery rate. These frogs have a keystone role in nutrient cycling and food webs, and their prompt recovery might represent an important step for the functional recovery of forests. Nevertheless, the strong interspecific differences stress the complexity of these processes.

Retraction: Mesenchymal Stem Cells: Are They Suitable for Systemic Injection? An In Vitro Study

This article is being retracted because another article was published using the same data, but under a different title, in Microvascular Research.