Bone Marrow-Derived Progenitor Cells Augment Venous Remodeling in a Mouse Dorsal Skinfold Chamber Model

The delivery of bone marrow-derived cells (BMDCs) has been widely used to stimulate angiogenesis and arteriogenesis. We identified a progenitor-enriched subpopulation of BMDCs that is able to augment venular remodeling, a generally unexplored area in microvascular research. Two populations of BMDCs, whole bone marrow (WBM) and Lin−/Sca-1+ progenitor cells, were encapsulated in sodium alginate and delivered to a mouse dorsal skinfold chamber model. Upon observation that encapsulated Sca-1+ progenitor cells enhance venular remodeling, the cells and tissue were analyzed on structural and molecular levels. Venule walls were thickened and contained more nuclei after Sca-1+ progenitor cell delivery. In addition, progenitors expressed mRNA transcript levels of chemokine (C-X-C motif) ligand 2 (CXCL2) and interferon gamma (IFNγ) that are over 5-fold higher compared to WBM. Tissues that received progenitors expressed significantly higher protein levels of vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and platelet derived growth factor-BB (PDGF-BB) compared to tissues that received an alginate control construct. Nine days following cell delivery, tissue from progenitor recipients contained 39% more CD45+ leukocytes, suggesting that these cells may enhance venular remodeling through the modulation of the local immune environment. Results show that different BMDC populations elicit different microvascular responses. In this model, Sca-1+ progenitor cell-derived CXCL2 and IFNγ may mediate venule enlargement via modulation of the local inflammatory environment

Murine 5T multiple myeloma cells induce angiogenesis in vitro and in vivo

Multiple myeloma is a B cell malignancy. Recently, it has been demonstrated that bone marrow samples of patients with multiple myeloma display an enhanced angiogenesis. The mechanisms involved seem to be multiple and complex. We here demonstrate that the murine 5T multiple myeloma models are able to induce angiogenesis in vitro by using a rat aortic ring assay and in vivo by determining the microvessel density. The rat aortic rings cultured in 5T multiple myeloma conditioned medium exhibit a higher number of longer and more branched microvessels than the rings cultured in control medium. In bone marrow samples from 5T multiple myeloma diseased mice, a statistically significant increase of the microvessel density was observed when compared to bone marrow samples from age-matched controls. The angiogenic phenotype of both 5T multiple myeloma cells could be related, at least in part, to their capacity to produce vascular endothelial growth factor. These data clearly demonstrate that the 5T multiple myeloma models are good models to study angiogenesis in multiple myeloma and will allow to unravel the mechanisms of neovascularisation, as well as to test new putative inhibitors of angiogenesis

Stem Cell Therapy: Pieces of the Puzzle

Acute ischemic injury and chronic cardiomyopathies can cause irreversible loss of cardiac tissue leading to heart failure. Cellular therapy offers a new paradigm for treatment of heart disease. Stem cell therapies in animal models show that transplantation of various cell preparations improves ventricular function after injury. The first clinical trials in patients produced some encouraging results, despite limited evidence for the long-term survival of transplanted cells. Ongoing research at the bench and the bedside aims to compare sources of donor cells, test methods of cell delivery, improve myocardial homing, bolster cell survival, and promote cardiomyocyte differentiation. This article reviews progress toward these goals

Artisanal fish fences pose broad and unexpected threats to the tropical coastal seascape

Gear restrictions are an important management tool in small-scale tropical fisheries, improving sustainability and building resilience to climate change. Yet to identify the management challenges and complete footprint of individual gears, a broader systems approach is required that integrates ecological, economic and social sciences. Here we apply this approach to artisanal fish fences, intensively used across three oceans, to identify a previously underrecognized gear requiring urgent management attention. A longitudinal case study shows increased effort matched with large declines in catch success and corresponding reef fish abundance. We find fish fences to disrupt vital ecological connectivity, exploit > 500 species with high juvenile removal, and directly damage seagrass ecosystems with cascading impacts on connected coral reefs and mangroves. As semi-permanent structures in otherwise open-access fisheries, they create social conflict by assuming unofficial and unregulated property rights, while their unique high-investment-low-effort nature removes traditional economic and social barriers to overfishing