Macrophage-mediated angiogenic activation of outgrowth endothelial cells in co-culture with primary osteoblasts.

The successful vascularisation of complex tissue engineered constructs for bone regeneration is still a major challenge in the field of tissue engineering. In this context, co-culture systems of endothelial cells and osteoblasts represent a promising approach to advance the formation of a stable vasculature as well as an excellent in vitro model to identify factors that positively influence bone healing processes, including angiogenesis. Under physiological conditions, the activation phase of angiogenesis is mainly induced by hypoxia or inflammation. Inflammatory cells such as macrophages secrete proinflammatory cytokines and proangiogenic growth factors, finally leading to the formation of…

Third Eular Workshop on Rheumatology Research

Osteoclast-like Giant Cell Tumor of the Pancreas With Ductal Adenocarcinoma: Case Report with Novel Data on Histogenesis

Kommentar auf Anforderung der Schriftleitung

Impaired in vivo vasculogenic potential of endothelial progenitor cells in comparison to human umbilical vein endothelial cells in a spheroid-based implantation model.

Objectives:  Neovascularization represents a major challenge in tissue engineering applications since implantation of voluminous grafts without sufficient vascularity results in hypoxic cell death of implanted cells. An attractive therapeutic approach to overcome this is based on co-implantation of endothelial cells to create vascular networks. We have investigated the potential of human endothelial progenitor cells (EPC) to form functional blood vessels in vivo in direct comparison to vascular-derived endothelial cells, represented by human umbilical vein endothelial cells (HUVEC). Materials and methods:  EPCs were isolated from human peripheral blood, expanded in vitro and analysed in vit…

Expression of fibronectin splice variants and oncofetal glycosylated fibronectin in the synovial membranes of patients with rheumatoid arthritis and osteoarthritis

The aim of this study was to define and compare the expression of fibronectin (Fn) isoforms in synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA).Using monoclonal antibodies specific for total Fn, extra domain (ED)-A Fn, ED-B Fn, and oncofetal glycosylated Fn, we studied the expression of the Fn isoforms in synovium. Furthermore, in situ hybridization for the detection of ED-B Fn mRNA including a double labeling technique for the detection of cell type was applied.Strong expression of total Fn, ED-A Fn, oncofetal glycosylated Fn and, to a lesser extent, ED-B Fn could be demonstrated in the synovial lining layer in both RA and OA. Stromal and vessel expression…

Multinucleated giant cells in the implant bed of bone substitutes are foreign body giant cells-New insights into the material-mediated healing process

In addition to macrophages, multinucleated giant cells (MNGCs) are involved in the tissue reaction to a variety of biomaterials. Especially in the case of bone substitute materials it has been assumed that the MNGCs are osteoclasts, based on the chemical and physical similarity of many materials to the calcified matrix and the bony environment in which they are used. However, many studies indicate that these cells belong to the cell line of the foreign body giant cells (FBGCs), which are of "inflammatory origin", although they have been shown to possess both a pro- and also anti-inflammatory phenotype. Moreover, no information is available about their role in the tissue reaction to bone sub…

Monocyte preseeding leads to an increased implant bed vascularization of biphasic calcium phosphate bone substitutes via vessel maturation

The present study analyzes the influence of the addition of monocytes to a biphasic bone substitute with two granule sizes (400-700 μm and 500-1000 μm). The majority of the added monocytes was detectable as mononuclear cells, while also low amounts of (chimeric) multinucleated giant cells (MNGCs) were found. No increase in the total number of MNGCs was established, but a significantly increased percent vascularization. Altogether, the results show that the added monocytes become involved in the tissue response to a biomaterial without marked changes in the overall reaction. Monocyte addition enables an increased implant bed vascularization especially via induction of vessel maturation and, …

Massive Adenomyose bei einer Patientin mit Uterus septus completus

Septate uterus is a malformation caused by the defective resorption of the Mullerian ducts. It may be incomplete, or -- less frequently -- complete. We present a case of a uterus septus completus with special emphasis on the endometrial changes. We describe a 46-year-old female patient (nullipara) with a known uterus septus suffering from hypermenorrhea. Sonography demonstrated a massively enlarged uterus with several nodes. Hysterectomy was performed and tissue specimens were routinely processed. Macroscopical examination revealed a 1 230 g-weight uterus septus completus. In particular, the myometrium was enlarged and exhibited a cystic cut surface with several nodes measuring up to 4.5 cm…

Superoxide Flux in Endothelial Cells via the Chloride Channel-3 Mediates Intracellular Signaling

Reactive oxygen species (ROS) have been implicated in both cell signaling and pathology. A major source of ROS in endothelial cells is NADPH oxidase, which generates superoxide (O2.−) on the extracellular side of the plasma membrane but can result in intracellular signaling. To study possible transmembrane flux of O2.−, pulmonary microvascular endothelial cells were preloaded with the O2.−-sensitive fluorophore hydroethidine (HE). Application of an extracellular bolus of O2.−resulted in rapid and concentration-dependent transient HE oxidation that was followed by a progressive and nonreversible increase in nuclear HE fluorescence. These fluorescence changes were inhibited by superoxide dism…

Biomimetic strategy towards gelatin coatings on PET. Effect of protocol on coating stability and cell-interactive properties

Gelatin-modified poly(ethylene terephthalate) (PET) surfaces have been previously realized via an intermediate dopamine coating procedure that resulted in surfaces with superior haemocompatibility compared to unfunctionalized PET. The present study addresses the biocompatibility assessment of these coated PET surfaces. In this context, the stability of the gelatin coating upon exposure to physiological conditions and its cell-interactive properties were investigated. The proposed gelatin–dopamine-PET surfaces showed an increased protein coating stability up to 24 days and promoted the attachment and spreading of both endothelial cells (ECs) and smooth muscle cells (SMCs). In parallel, physi…

Comparative study assessing effects of sonic hedgehog and VEGF in a human co-culture model for bone vascularisation strategies.

The morphogen sonic hedgehog (Shh) seems to mediate adult repair processes in bone regeneration and vascularisation. In this study we investigated the effects of Shh on co-cultures consisting of human primary osteoblasts and outgrowth endothelial cells in terms of angiogenic activation and vessel maturation in comparison to the treatment with the commonly used proangiogenic factor, VEGF. Both, stimulation with VEGF or Shh, leads to an increase in the formation of microvessel-like structures compared to untreated controls. In contrast to VEGF, proangiogenic effects by Shh could already be observed after 24 h of treatment. Nevertheless, after 14 days the angiogenic activity of OEC was compara…