Dimethyl Fumarate ameliorates pulmonary arterial hypertension and lung fibrosis by targeting multiple pathways.

Pulmonary arterial hypertension (PAH) is a fatal condition for which there is no cure. Dimethyl Fumarate (DMF) is an FDA approved anti-oxidative and anti-inflammatory agent with a favorable safety record. The goal of this study was to assess the effectiveness of DMF as a therapy for PAH using patient-derived cells and murine models.

TSP1-CD47 signaling is upregulated in clinical pulmonary hypertension and contributes to pulmonary arterial vasculopathy and dysfunction.

Aims: Thrombospondin-1 (TSP1) is a ligand for CD47 and TSP1 mice are protected from pulmonary hypertension (PH). We hypothesized the TSP1-CD47 axis is upregulated in human PH and promotes pulmonary arterial vasculopathy.

Methods And Results: We analyzed the molecular signature and functional response of lung tissue and distal pulmonary arteries (PAs) from individuals with (n = 23) and without (n = 16) PH.

Implanted scaffold-free prevascularized constructs promote tissue repair.

To evaluate the anastomotic potential of prevascular tissue constructs generated from scaffold-free self-assembly of human endothelial and fibroblast cells, tissue constructs were implanted into athymic mice and immune-competent rats. Analysis of xenografts placed into hind limb muscle defects showed vascular anastomotic activity by 3 days after implantation and persisting for 2 weeks. Integration of the implanted prevascular tissue constructs with the host circulatory system was evident from presence of red blood cells in the implant as early as 3 days after implantation.

Self-assembly of prevascular tissues from endothelial and fibroblast cells under scaffold-free, nonadherent conditions.

To advance the emerging field of bioengineered prevascularized tissues, we investigated factors that control primary vascular network formation in scaffold-free, high-density cell suspension-derived tissues. Fabricating primary vascular networks in a scaffold-free system requires endothelial cells (ECs) and extracellular matrix (ECM)-producing cells that act together to elaborate a permissive matrix. We report findings on the effects to vascular patterning induced by altering the ratio of human endothelial to human fibroblast cells.

Scaffold-free tissue engineering: organization of the tissue cytoskeleton and its effects on tissue shape.

Work described herein characterizes tissues formed using scaffold-free, non-adherent systems and investigates their utility in modular approaches to tissue engineering. Immunofluorescence analysis revealed that all tissues formed using scaffold-free, non-adherent systems organize tissue cortical cytoskeletons that appear to be under tension. Tension in these tissues was also evident when modules (spheroids) were used to generate larger tissues.

Extracellular matrix powder protects against bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis refers to a group of lung diseases characterized by inflammation, fibroblast proliferation, and excessive collagen deposition. Although the mechanisms underlying pulmonary fibrosis are poorly understood, current evidence suggests that epithelial injury contributes to the development of fibrosis. Regenerative medicine approaches using extracellular matrix (ECM) scaffolds have been shown to promote site-specific tissue remodeling.

Hydrated xenogeneic decellularized tracheal matrix as a scaffold for tracheal reconstruction.

Tracheal injury is a rare but complex problem. Primary tracheal reconstructions are commonly performed, but complications such as tension and inadequate vascular supply limit the length of surgical resection. The objective of the present study was to determine whether a hydrated, decellularized porcine tracheal extracellular matrix showed the potential to serve as a functional tracheal replacement graft.

Preparation of cardiac extracellular matrix from an intact porcine heart.

Whole organ engineering would benefit from a three-dimensional scaffold produced from intact organ-specific extracellular matrix (ECM). The microenvironment and architecture provided by such a scaffold would likely support site-appropriate cell differentiation and spatial organization. The methods to produce such scaffolds from intact organs require customized decellularization protocols.