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Targeted therapies using biopharmaceuticals are of growing clinical importance in disease treatment. Currently, there are several limitations of protein-based therapeutics (biologicals), including suboptimal biodistribution, lack of stability, and systemic side effects. A promising approach to overcoming these limitations could be a therapeutic cell-loaded 3D construct consisting of a suitable matrix component that harbors producer cells continuously secreting the biological of interest. Here, the recombinant spider silk proteins eADF4(C16), eADF4(C16)-RGD, and eADF4(C16)-RGE have been processed together with HEK293 producer cells stably secreting the highly traceable reporter biological TNFR2-Fc-GpL, a fusion protein consisting of the extracellular domain of TNFR2, the Fc domain of human IgG1, and the luciferase of

Introduction: For the regeneration of large volume tissue defects, the interaction between angiogenesis and osteogenesis is a crucial prerequisite. The surgically induced angiogenesis by means of a...

OBJECTIVE Transplantation of prefabricated tissue-engineered flaps can be a potential alternative for healing large tissue defects. Providing adequate vascular supply for an engineered tissue construct is one of the key points in establishing successful tissue engineering based treatment approaches. In tissue engineering-based vascularization techniques like the AV loop, vascular grafts with high angiogenic potential can help to enhance neovascularization and tissue formation. Therefore, our study aimed to compare the angiogenic potential of vascular grafts from different locations in the rat. METHODS The angiogenic activity was investigated by an ex vivo vessel outgrowth ring assay using 1 mm height vascular segments embedded in fibrin for two weeks. RESULTS Maximum vessel outgrowth was observed on days 10-12. Upper extremity vessels exhibited stronger outgrowth than lower extremity vessels. Moreover, arterial vessels demonstrated higher angiogenic potential compared to venous vessels. CONCLUSION Collectively, our ex vivo findings suggest that upper extremity arterial vessels have a higher angiogenic capacity, which could be used to improve neovascularization and tissue formation in tissue engineering.

Hexagonal boron nitride (h-BN) monolayers were grown on Pt(110) using borazine as a precursor molecule. The resulting surface structure was studied by scanning tunneling microscopy, low-energy electron diffraction, and density functional theory calculations. Borazine fragments reduce the roughening temperature of pristine Pt(110) ( Tr = 1090 K); consequently, growth below T = 1100 K results in a serrated h-BN/Pt(110) surface with small terraces, defects, and domain boundaries. Surprisingly, h-BN deposition at T > 1100 K yields large terraces covered by a carpet-like single-domain h-BN monolayer. Despite the incommensurability and different symmetry, the epitaxial growth is almost perfect. The key to this counterintuitive behavior is the "soft" Pt(110) surface responding to the h-BN overlayer in two ways: First, the (1 × 2)-missing-row (m.r.) reconstruction is converted into a (1 × n)-m.r. reconstruction with a regular alternation of n = 5 and 6, yielding a superperiodicity of the Moire pattern. Second, the remaining rows experience significant relaxations. Some Pt surface atoms are mobile underneath the h-BN monolayer, even at room temperature. Under growth conditions, the top metal layer is disordered and highly mobile, rendering the h-BN growth comparable to that on liquid gold. Such a mechanism may be of general relevance for the epitaxial growth of 2D materials. Because epitaxial deposition of Pt(110) on various substrates has been demonstrated, the present system appears scalable, and its regular 1D grooves render it a promising template for nanowire arrays.

Due to its low immunogenic potential and the possibility to fine-tune their properties, materials made of recombinant engineered spider silks are promising candidates for tissue engineering applications. However, vascularization of silk-based scaffolds is one critical step for the generation of bioartificial tissues and consequently for clinical application. To circumvent insufficient vascularization, the surgically induced angiogenesis by means of arteriovenous loops (AVL) represents a highly effective methodology. Here, previously established hydrogels consisting of nano-fibrillary recombinant eADF4(C16) were transferred into Teflon isolation chambers and vascularized in the rat AVL model over 4 weeks. To improve vascularization, also RGD-tagged eADF4(C16) hydrogels were implanted in the AVL model over 2 and 4 weeks. Thereafter, the specimen were explanted and analyzed using histology and microcomputed tomography. We were able to confirm biocompatibility and tissue formation over time. Functionalizing eADF4(C16) with RGD-motifs improved hydrogel stability and enhanced vascularization even outperforming other hydrogels, such as fibrin. This study demonstrates that the scaffold ultrastructure as well as biofunctionalization with RGD-motifs are powerful tools to optimize silk-based biomaterials for tissue engineering applications.

Due to its low immunogenic potential and the possibility to fine-tune their properties, materials made of recombinant engineered spider silks are promising candidates for tissue engineering applications. However, vascularization of silk-based scaffolds is one critical step for the generation of bioartificial tissues and consequently for clinical application. To circumvent insufficient vascularization, the surgically induced angiogenesis by means of arteriovenous loops (AVL) represents a highly effective methodology. Here, previously established hydrogels consisting of nano-fibrillary recombinant eADF4(C16) were transferred into Teflon isolation chambers and vascularized in the rat AVL model over 4 weeks. To improve vascularization, also RGD-tagged eADF4(C16) hydrogels were implanted in the AVL model over 2 and 4 weeks. Thereafter, the specimen were explanted and analyzed using histology and microcomputed tomography. We were able to confirm biocompatibility and tissue formation over time. Functionalizing eADF4(C16) with RGD-motifs improved hydrogel stability and enhanced vascularization even outperforming other hydrogels, such as fibrin. This study demonstrates that the scaffold ultrastructure as well as biofunctionalization with RGD-motifs are powerful tools to optimize silk-based biomaterials for tissue engineering applications.

Metal halides are a class of layered materials with promising electronic and magnetic properties persisting down to the two-dimensional limit. While most recent studies focused on the trihalide components of this family, the rather unexplored metal dihalides are also van der Waals layered systems with distinctive magnetic properties. Here we show that the dihalide NiBr2 grows epitaxially on a Au(111) substrate and exhibits semiconducting and magnetic behavior starting from a single layer. Through a combination of a low-temperature scanning-tunneling microscopy, low-energy electron diffraction, X-ray photoelectron spectroscopy, and photoemission electron microscopy, we identify two competing layer structures of NiBr2 coexisting at the interface and a stoichiometrically pure layer-by-layer growth beyond. Interestingly, X-ray absorption spectroscopy measurements revealed a magnetically ordered state below 27 K with in-plane magnetic anisotropy and zero-remanence in the single layer of NiBr2/Au(111), which we attribute to a noncollinear magnetic structure. The combination of such two-dimensional magnetic order with the semiconducting behavior down to the 2D limit offers the attractive perspective of using these films as ultrathin crystalline barriers in tunneling junctions and low-dimensional devices., D.B. acknowledges funding from the Austrian Science Fund (FWF) under the Erwin Schrödinger fellowship agreement (project number: J4395-N). C.G.-O. and M.P.-D. acknowledge funding of the Ph.D. fellowship from the MPC Foundation. We gratefully acknowledge financial support from Spanish AEI (Grant Nos. PID2019-107338RB-C6, RTI-2018-095303-C53, and the Maria de Maeztu Units of Excellence Programme MDM-2016-0618) and from the European Union (EU) through Horizon 2020 (SUPERTED Grant No. 800923), from Interred POCTEFA V-A Spain/France/Andorra Program (EFA 194/16/TNSI), the Basque Government (GV/EJ) under grants IT-1255-19, and the European Regional Development Fund. P.G. acknowledges funding from MINECO Grant No. FIS2016-78591-C3-2-R and FLAG-ERA Grant No. PCI2019-111908-2.

The authors study the band structure of a hexagonal Boron Nitride monolayer on a Pt(110) surface with rectangular symmetry using angle-resolved photoemission and density functional theory, and show that the bonding is dominated by van-der-Waals forces.

Abdominal free flaps such as the muscle sparing transverse rectus abdominis myocutaneous (ms-TRAM) or deep inferior epigastric artery perforator (DIEP) flap represent the gold standard in autologous breast reconstruction. We describe a salvage procedure during bilateral free flap breast reconstruction due to insufficient venous drainage using a venous cross-over bypass. A 54-year-old woman with a thrombosis of the left subclavian port-system in the medical history was elected for simultaneous bilateral breast reconstruction with ms-TRAM and DIEP flaps. Intraoperatively, a venous congestion of the DIEP flap, which was connected to the left cranial internal mammary vessels, appeared. In the absence of sufficient ipsilateral venous recipient vessels, we performed a salvage procedure requiring a 15 cm small saphenous vein graft and presternal subcutaneous tunneling. The flap vein was anastomosed end-to-end with the contralateral caudal internal mammary vein using a coupler system. The postoperative course was uneventful and both flaps survived. We describe the cross-over venous emergency bypass as a useful tool in unexpected venous thrombosis during bilateral free flap breast reconstruction.

Background: Breast cancer is the most common malignancy in women. The interdisciplinary treatment is based on the histological tumor type, the TNM classification, and the patient's wishes. Following tumor resection and (neo-) adjuvant therapy strategies, breast reconstruction represents the final step in the individual interdisciplinary treatment plan. Although manifold flaps have been described, abdominal free flaps, such as the deep inferior epigastric artery perforator (DIEP) or the muscle-sparing transverse rectus abdominis myocutaneous (ms-TRAM) flap, are the current gold standard for autologous breast reconstruction. This retrospective study focuses on the safety of autologous breast reconstruction upon mastectomy using abdominal free flaps. Methods: From April 2012 until December 2018, 193 women received 217 abdominal free flaps for autologous breast reconstruction at the University Hospital of Erlangen. For perforator mapping, we performed computed tomography angiography (CTA). Venous anastomosis was standardized using a ring pin coupler system, and flap perfusion was assessed with fluorescence angiography. A retrospective analysis was performed based on medical records, the surgery report, and follow-up of outpatient course. Results: In most cases, autologous breast reconstruction was performed as a secondary reconstructive procedure after mastectomy and radiotherapy. In total, 132 ms1-TRAM, 23 ms2-TRAM, and 62 DIEP flaps were performed with 21 major complications (10%) during hospital stay including five free flap losses (2.3%). In all cases of free flap loss, we found an arterial thrombosis as the main cause. In 24 patients a bilateral breast reconstruction was performed without free flap loss. The majority of free flaps (96.7%) did not need additional supercharging or turbocharging to improve venous outflow. Median venous coupler size was 2.5 mm (range, 1.5–3.5 mm). Conclusion: Using CTA, intraoperative fluorescence angiography, titanized hernia meshes for rectus sheath reconstruction, and venous coupler systems, autologous breast reconstruction with DIEP or ms-TRAM free flaps is a safe and standardized procedure in high-volume microsurgery centers.

The microvascular endothelial network is essential for bone formation and regeneration. In this context, endothelial cells not only support vascularization but also influence bone physiology via cell contact‐dependent mechanisms. In order to improve vascularization and osteogenesis in tissue engineering applications, several strategies have been developed. One promising approach is the coapplication of endothelial and adipose derived stem cells (ADSCs). In this study, we aimed at investigating the best ratio of human umbilical vein endothelial cells (HUVECs) and osteogenic differentiated ADSCs with regard to proliferation, apoptosis, osteogenesis and angiogenesis. For this purpose, cocultures of ADSCs and HUVECs with ratios of 25%:75%, 50%:50% and 75%:25% were performed. We were able to prove that cocultivation supports proliferation whereas apoptosis was unidirectional decreased in cocultured HUVECs mediated by a p‐BAD‐dependent mechanism. Moreover, coculturing ADSCs and HUVECs stimulated matrix mineralization and the activity of alkaline phosphatase (ALP). Increased gene expression of the proangiogenic markers eNOS, Flt, Ang2 and MMP3 as well as sprouting phenomena in matrigel assays proved the angiogenic potential of the coculture. In summary, coculturing ADSCs and HUVECs stimulates proliferation, cell survival, osteogenesis and angiogenesis particularly in the 50%:50% coculture.

Vascularization of bioartificial tissues can be significantly enhanced by the generation of an arteriovenous (AV) loop. Besides the surgical vascularization, the choice of the scaffold and the applied cells are indispensable cofactors. The combination of alginate dialdehyde and gelatin (ADA-GEL) and mesenchymal stem cells (MSCs) is a promising approach with regard to biocompatibility, biodegradation, as well as de novo tissue formation. In this study, we targeted the investigation of the vascularization of ADA-GEL with and in the absence of encapsulated MSCs in the AV loop model. A Teflon chamber filled with ADA-GEL microcapsules was placed in the groin of Lewis rats and an AV loop was placed into the chamber. Group A encompassed the ADA-GEL without MSCs, whereas group B contained 2 × 10

It is well known that dust resistivity and particle size play a major role in electrostatic precipitation processes. The electrostatic precipitator design also has to be adapted for carbon rich fly ashes such as those found in heavy fuel oil combustion plants. In this work, an ash sample from an electrostatic precipitator downstream an industrial biomass boiler operated under poor combustion conditions was air classified into 5 particle size fractions. Those fractions were then analyzed regarding chemical composition, loss on ignition, particle size distribution and dust resistivity. Furthermore scanning electron as well as optical microscope images were taken to investigate particle structure and shape. Diverse types of particles were found in the different fractions, varying from unburned coal particles to inorganic sand-like particles. It was also found that chemical composition as well as resistivity varied significantly with different size fractions. During resistivity measurements, fluctuating voltage and current values were recognized, similar to what can be seen during the back-corona phenomenon, but found at medium resistivity values. Furthermore, suggestions for an electrostatic precipitator design will be given based on findings in this study.

The electrochemical lithiation/delithiation behavior of self-organized amorphous and anatase titanium dioxide (TiO2) nanotubes (NTs) is analyzed by means of electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS). The bulk lithiation properties are governed by the different phase transitions in amorphous and anatase TiO2. While in the case of amorphous nanotubes the phase transition only leads to a thermodynamic limitation of the bulk Li content, it additionally limits the lithiation kinetics for the anatase case. This kinetic constraint is found to originate from underlithiation of the anatase TiO2–x bulk caused by the instant first phase transition during lithium insertion. Together with the surface lithiation properties, it leads to different lithiation characteristics. Amorphous nanotubes are characterized by a reversible surface chemistry and thus pseudocapacitive lithiation/delithiation behavior. As a result, amorphous TiO2 nanotubes show higher overall capacities due...

In situ tissue engineering is an emerging field aiming at the generation of ready-to-use three-dimensional tissues. One solution to supply a proper vascularization of larger tissues to provide oxygen and nutrients is the arteriovenous loop (AVL) model. However, for this model, suitable scaffold materials are needed that are biocompatible/non-immunogenic, slowly degradable, and allow vascularization. Here, we investigate the suitability of the known gelatin methacryloyl (GelMA)-based hydrogel for in-situ tissue engineering utilizing the AVL model. Rat AVLs are embedded by two layers of GelMA hydrogel in an inert PTFE chamber and implanted in the groin. Constructs were explanted after 2 or 4 weeks and analyzed. For this purpose, gross morphological, histological, and multiphoton microscopic analysis were performed. Immune response was analyzed based on anti-CD68 and anti-CD163 staining of immune cells. The occurrence of matrix degradation was assayed by anti-MMP3 staining. Vascularization was analyzed by anti-α-smooth muscle actin staining, multiphoton microscopy, as well as expression analysis of 53 angiogenesis-related proteins utilizing a proteome profiler angiogenesis array kit. Here we show that GelMA hydrogels are stable for at least 4 weeks in the rat AVL model. Furthermore, our data indicate that GelMA hydrogels are biocompatible. Finally, we provide evidence that GelMA hydrogels in the AVL model allow connective tissue formation, as well as vascularization, introducing multiphoton microscopy as a new methodology to visualize neovessel formation originating from the AVL. GelMA is a suitable material for in situ and in vivo TE in the AVL model.

Adsorption, desorption and fragmentation of borazine on Pt(110) are studied by temperature-programmed desorption, ultraviolet photoemission spectroscopy, workfunction measurements and density functional theory. Borazine adsorbs in part dissociatively, forming an upright (B3N3H5˙)ads adsorption complex. Radicals with a N–Pt bond are weakly bound and desorb recombinatively following second-order kinetics. Radicals with a B–Pt bond are similar in binding strength to the molecularly adsorbed species, which binds through dispersive forces to the (111) facets of the (1 × 2) reconstructed Pt(110). Both do not desorb but are dehydrogenated beyond T = 150 K. As T approaches 600 K the B–N ring progressively breaks down into its atomic constituents. The borazine ice multilayer is capable of trapping significant amounts of hydrogen. Previous studies of borazine adsorption on other transition metal surfaces yield a very similar pattern. Reported multiple molecular desorption peaks are artefacts. Implications for the nucleation and growth of h-BN monolayers at high temperatures are discussed.

The surgically induced angiogenesis by means of arteriovenous (AV) loops represents a powerful method to significantly enhance vascularization of biomaterials. Regarding tissue engineering applications, spider silk is a promising biomaterial with a good biocompatibility and slow biodegradation. This study aims at investigating vascularization as well as

Vascularization is important for bone development, fracture healing and engineering of artificial bone tissue. In the context of bone tissue engineering, it was shown that coimplantation of human primary umbilical vein endothelial cells (HUVECs) and human osteoblasts (hOBs) results in the formation of functional blood vessels and enhanced bone regeneration. Implanted endothelial cells do not only contribute to blood vessel formation, but also support proliferation, cell survival and osteogenic differentiation of coimplanted hOBs. These effects are partially mediated by direct heterotypic cell contacts. In a previous report we could show that cocultivated hOBs strongly increase the expression of genes involved in extracellular matrix (ECM) formation in HUVECs, suggesting that ECM may be involved in the intercellular communication between hOBs and HUVECs. The present study aimed at investigating whether comparable changes occur in hOBs. We therefore performed a microarray analysis of hOBs cultivated in direct contact with HUVECs, revealing 1,004 differentially expressed genes. The differentially expressed genes could be assigned to the functional clusters ECM, proliferation, apoptosis and osteogenic differentiation. The microarray data could be confirmed by performing quantitative real time RT-PCR on selected genes. Furthermore, we could show that the ECM produced by HUVECs increased the expression of the osteogenic differentiation marker alkaline phosphatase (ALP) in hOBs. In summary, our data demonstrate that HUVECs provoke complex changes in gene expression patterns in cocultivated hOBs and that ECM plays and important role in this interaction. J. Cell. Biochem. 117: 1869-1879, 2016. © 2016 Wiley Periodicals, Inc.

Integrating bioartificial tissues into the host vasculature is a prerequisite for tissue engineering applications. Endothelial progenitor cells (EPCs) display a high angiogenic potential and a low donor-site morbidity, making them ideal for tissue engineering applications. In our study we used a murine EPC cell line (T17b) and rat mesenchymal stem cells (MSCs) for cocultivation experiments. MSCs were cocultured with increasing T17b EPC amounts. Furthermore, MSCs in monoculture were treated with conditioned medium (CM) from T17b EPCs and T17b EPCs were treated with CM from MSCs. Proliferation and apoptosis were quantified with a bromodeoxyuridine ELISA and a DNA fragmentation ELISA, respectively. Osteogenic differentiation was detected with an alkaline phosphatase assay and bone morphogenetic protein-2 ELISA. The production of proangiogenic molecules was measured with a matrix metalloproteinase-3 and vascular endothelial growth factor ELISA as well as nitric oxide assay. We could show that T17b EPCs stimulated MSC proliferation but not vice versa. On the other hand, MSCs promoted the cell survival of EPCs. The growth-inducing and antiapoptotic effects were dependent on heterotypic cell contacts and paracrine mediators. Moreover, proangiogenic growth factors were found in the coculture. Collectively, our results indicate that the coapplication of MSCs and T17b EPCs provides new perspectives for tissue engineering applications.

Scalp reconstruction is a challenging task for the reconstructive surgeon. In consideration of the anatomical and cosmetic characteristics, the defect depth and size, an armamentarium of reconstructive procedures ranging from skin grafts over local flaps to free tissue transfer has been described. In this 10-year retrospective study, 85 operative procedures for scalp reconstruction were performed at our department. The underlying entity, defect size/depth, reconstructive procedure, complications, and mean hospital stay were analyzed. In most cases, scalp reconstruction was necessary after oncologic resection (67%) or radiation therapy (16%). A total of 85 operative procedures were performed for scalp reconstruction including local flaps (n = 50), free tissue transfer (n = 18), and skin grafts (n = 17). Regarding the complication rate, we could detect an overall major complication rate of 16.5% with one free flap loss. Briefly, local flaps are an adequate and safe procedure for limited scalp defects. In the case of extensive scalp defects affecting the calvarium, prior multiple surgical interventions and/or radiation, we prefer free tissue transfer.

Sinter plant off-gas is usually de-dusted by electrostatic precipitators. Compliance with the dust emission limits is often difficult because of the high specific resistivity of the emitted dust. Mechanical properties of the dust are also relevant for the electrostatic precipitator design. Dust samples from the four consecutive electrostatic precipitator fields were characterized in this study. Most measured parameters showed a considerable variation in the various dust samples. The particle size of the dust as well as its bulk density continuously decreased from the first field to the fourth field. The flowability of the dusts was generally bad and decreased from the first to the last field. In contrast, the wall friction angles with structural steel were quite constant at approximately 30°. The Fe content was lower in the dust from the last two fields while the concentration of K, Na, Cl(-) and [Formula: see text] was significantly higher. At the same time the particle density was lower. The maximum specific dust resistivity for the first field and second field dust was approximately 3 × 10(11) Ω cm and no signs for the occurrence of back corona were detected. For the dusts from the last two fields the maximum value was approximately 2 × 10(12) Ω cm. Back corona was observed in the temperature range from 120°C to 210°C. In this area the dust resistivity values were higher than 4 × 10(11) Ω cm.

Vascularization is important for bone development, fracture healing and engineering of artificial bone tissue. In the context of bone tissue engineering, it was shown that coimplantation of human primary umbilical vein endothelial cells (HUVECs) and human osteoblasts (hOBs) results in the formation of functional blood vessels and enhanced bone regeneration. Implanted endothelial cells do not only contribute to blood vessel formation, but also support proliferation, cell survival and osteogenic differentiation of coimplanted hOBs. These effects are partially mediated by direct heterotypic cell contacts. In a previous report we could show that cocultivated hOBs strongly increase the expression of genes involved in extracellular matrix (ECM) formation in HUVECs, suggesting that ECM may be involved in the intercellular communication between hOBs and HUVECs. The present study aimed at investigating whether comparable changes occur in hOBs. We therefore performed a microarray analysis of hOBs cultivated in direct contact with HUVECs, revealing 1,004 differentially expressed genes. The differentially expressed genes could be assigned to the functional clusters ECM, proliferation, apoptosis and osteogenic differentiation. The microarray data could be confirmed by performing quantitative real time RT-PCR on selected genes. Furthermore, we could show that the ECM produced by HUVECs increased the expression of the osteogenic differentiation marker alkaline phosphatase (ALP) in hOBs. In summary, our data demonstrate that HUVECs provoke complex changes in gene expression patterns in cocultivated hOBs and that ECM plays and important role in this interaction. J. Cell. Biochem. 117: 1869-1879, 2016. © 2016 Wiley Periodicals, Inc.

Surrogate taxa as indicators for biodiversity are widely used in conservation biology and ecology. However, available studies on the congruence of species diversity patterns in different taxa yielded inconsistent results, and correlations between taxa were few. To conserve or restore biodiversity in agricultural landscapes, knowledge on the response of different taxa to management regimes is crucial. In the present study we evaluated the congruence of diversity and similarity patterns among three insect taxa, i.e., bees, grasshoppers, and aculeate wasps, in a mosaic landscape in the Swiss Alps comprising extensively used grassland under different management regimes. In addition, we studied the influence of land use on the diversity and species composition of the three taxa. While species numbers were not significantly correlated between any pair of taxa, community similarities were positively correlated between bees and grasshoppers. The number of red-listed species was not correlated with the total number of species in bees and in grasshoppers. None of the investigated taxa reflected the species numbers or community similarities of the other taxa well enough to qualify as a general indicator for biodiversity. Remarkably, land use clearly influenced species composition, while its effect on species numbers was not significant. All management regimes of the grassland in the study area contribute substantially to the overall diversity of the three insect taxa. Conserving the variety of agricultural land uses will be the most promising step towards the conservation of biodiversity in the study area.

Angiogenesis is a fundamental process in bone formation, remodeling, and regeneration. Moreover, for the regeneration of bone in tissue engineering applications, it is essential to support neovascularization. This can be achieved by cell-based therapies using primary endothelial cells, which are able to form functional blood vessels upon implantation. In bone composite grafts, coimplanted endothelial cells do not only support neovascularization but also support osteogenic differentiation of osteoblasts and osteoprogenitor cells. In this study, we investigated the effect of endothelial cells on proliferation and cell survival of human primary osteoblasts (hOBs) and human mesenchymal stem cells (MSCs). Human umbilical vein endothelial cells (HUVECs) stimulated hOB and MSC proliferation, whereas proliferation of HUVECs was unaffected by cocultured hOBs or MSCs. The effect of HUVEC cocultivation on hOB and MSC proliferation was more pronounced in direct cocultures than in indirect cocultures, indicating that this effect is at least partially dependent on the formation of heterotypic cell contacts between HUVECs and hOBs or MSCs. Furthermore, HUVEC cocultivation reduced low-serum induced apotosis of hOBs and MSCs by a mechanism involving increased phosphorylation and inactivation of the proapoptotic protein Bad. In summary, our experiments have shown that cocultured HUVECs increase the proliferation and reduce low-serum induced apoptosis of hOBs and MSCs.