Growth Of Human Endothelial Cells Research Articles

Lithium-Doped Titanium Dioxide-Based Multilayer Hierarchical Structure for Accelerating Nerve-Induced Bone Regeneration.

Despite considerable advances in artificial bone tissues, the absence of neural network reconstruction in their design often leads to delayed or ineffective bone healing. Hence, we propose a multilayer hierarchical lithium (Li)-doped titanium dioxide structure, constructed through microarc oxidation combined with alkaline heat treatment. This structure can induce the sustained release of Li ions, mimicking the environment of neurogenic osteogenesis characterized by high brain-derived neurotrophic factor (BDNF) expression. During in vitro experiments, the structure enhanced the differentiation of Schwann cells (SCs) and the growth of human umbilical vein endothelial cells (HUVECs) and mouse embryo osteoblast progenitor cells (MC3T3-E1). Additionally, in a coculture system, the SC-conditioned media markedly increased alkaline phosphatase expression and the formation of calcium nodules, demonstrating the excellent potential of the material for nerve-induced bone regeneration. In an in vivo experiment based on a rat distal femoral lesion model, the structure substantially enhanced bone healing by increasing the density of the neural network in the tissue around the implant. In conclusion, this study elucidates the neuromodulatory pathways involved in bone regeneration, providing a promising method for addressing bone deformities.

Methacrylated gelatin hydrogel conjugated with ε-polylysine and enriched with platelet-rich plasma for chronically infected wounds

While numerous hydrogel dressings are available for treating chronically infected wounds, their clinical application is impeded by intricate preparation processes, low mechanical strength, and frequent reliance on exogenous antimicrobial agents. The latter often leads to antibiotic misuse and compromises the bioactivity of cell growth-promoting substances. Therefore, the field of therapeutic treatment is faced with a pressing need to prepare high-mechanical-strength hydrogels through a facile procedure, achieving endogenous antibacterial characteristics and long-term healing abilities for chronically infected wounds. In this study, employing the Michael addition reaction principle, we conducted the conjugate addition of the natural antimicrobial poly amino acid, ε-polylysine (ε-PL), to gelatin methacrylate. This not only augmented the hydrogel’s mechanical strength but also preserved its antimicrobial efficacy. Subsequently, platelet-rich plasma (PRP), capable of releasing diverse growth factors, was introduced. Injectable and degradable hydrogels with high mechanical strength and water absorption were prepared through UV curing while retaining PRP bioactivity. The combination of PRP and ε-PL substantiated the enhanced antimicrobial properties and promotion of human umbilical vein endothelial cell growth, as validated through bacterial inhibition experiments, such as live-dead bacterial staining and cellular assays, including cell proliferation. Therefore, the as-developed PL-PRP hydrogel presents as a promising hydrogel dressing for the treatment of chronically infected wounds.

Abstract 2734: RC148, a novel bispecific antibody targeting PD-1 and VEGF for cancer immunotherapy

Abstract Vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic factors in modulating tumor microenvironment (TME), and the concentration of VEGF in TME is significantly higher than that of peripheral. Inhibiting VEGF can improve immunotherapy efficacy by modulating the TME, preventing angiogenesis and regulating immune cell populations. Combined anti-VEGF and anti-Programmed cell death protein 1 (PD-1)/Programmed cell death ligand (PD-L1) therapies have exerted potent antitumor effect in preclinic and clinic studies. Therefore, we developed a novel humanized IgG1 silenced bispecific antibody RC148 to target VEGF and PD-1. RC148 allows dimeric VEGF crosslinking and gradually enhances PD-1 binding activity, potentially reduces systemic toxicity of anti-VEGF therapy and enhances antitumor potency via VEGF trigged enrichment in tumor areas. In preclinical studies, RC148 blocks the binding of VEGF to VEGFR and PD-1 to PD-L1, prevents the growth and migration of human umbilical vein endothelial cells, enables efficient T cell activation, exhibited synergistic antitumor effects in rodent models and showed safety profiles in non-human primate studies. Citation Format: Jianmin Fang, Dong Li, Kaiyue Wu, Sisi Wang, Du Li, Guorui Zhao, Shenjun Li, Jing Jiang. RC148, a novel bispecific antibody targeting PD-1 and VEGF for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2734.

Bone Marrow Mesenchymal Stem Cell-derived Exosomal microRNA- 99b-5p Promotes Cell Growth of High Glucose-treated Human Umbilical Vein Endothelial Cells by Modulating THAP Domain Containing 2 Expression.

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) may function as novel candidates for treating diabetic wounds due to their ability to promote angiogenesis. This study investigated the effects of BMSC-exos on the growth and metastasis of human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG). The exosomes were separated from BMSCs and identified. The cell phenotype was detected by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and 5-ethynyl-2'-deoxyuridine, wound healing, and transwell assays, while the number of tubes was measured via tube formation assay. The RNA and protein expression levels were studied using reverse transcription-quantitative polymerase chain reaction and western blotting, whereas integration of microRNA-99b-5p (miR-99b-5p) with THAP domain containing 2 (THAP2) was confirmed via dual-luciferase reporter and RNA pull-down assays. Results of transmission electron microscopy, nanoparticle tracking analysis, and laser scanning confocal microscopy revealed that exosomes were successfully separated from BMSCs and endocytosed into the cytoplasm by HUVECs. Similarly, BMSC-exos were found to promote the growth of HG-treated HUVECs, while their growth was inhibited by suppressing miR-99b-5p. THAP2 was found to bind to miR-99b-5p, where THAP2 inhibition reversed the miR-99b-5p-induced effects on cell growth, migration, and tube numbers. In conclusion, miR-99b-5p in BMSC-exo protects HUVECs by negatively regulating THAP2 expression.

Strengthened Decellularized Porcine Valves via Polyvinyl Alcohol as a Template Improving Processability.

The heart valve is crucial for the human body, which directly affects the efficiency of blood transport and the normal functioning of all organs. Generally, decellularization is one method of tissue-engineered heart valve (TEHV), which can deteriorate the mechanical properties and eliminate allograft immunogenicity. In this study, removable polyvinyl alcohol (PVA) is used to encapsulate decellularized porcine heart valves (DHVs) as a dynamic template to improve the processability of DHVs, such as suturing. Mechanical tests show that the strength and elastic modulus of DHVs treated with different concentrations of PVA significantly improve. Without the PVA layer, the valve would shift during suture puncture and not achieve the desired suture result. The in vitro results indicate that decellularized valves treated with PVA can sustain the adhesion and growth of human umbilical vein endothelial cells (HUVECs). All results above show that the DHVs treated with water-soluble PVA have good mechanical properties and cytocompatibility to ensure post-treatment. On this basis, the improved processability of DHV treated with PVA enables a new paradigm for the manufacturing of scaffolds, making it easy to apply.

Comparison of Silk Hydrogels Prepared via Different Methods.

Silk fibroin (SF) hydrogels have garnered extensive attention in biomedical materials, owing to their superior biological properties. However, the challenges facing the targeted silk fibroin hydrogels involve chemical agents and shortfalls in performance. In this study, the silk fibroin hydrogels were prepared in different ways: sonication induction, chemical crosslinking, photopolymerization, and enzyme-catalyzed crosslinking. The SF hydrogels derived from photopolymerization exhibited higher compressive properties, with 124 Kpa fracture compressive stress and breaks at about 46% compression. The chemical crosslinking and enzyme-catalyzed silk fibroin hydrogels showed superior toughness, yet sonication-induced hydrogels showed brittle performance resulting from an increase in silk II crystals. The chemical-crosslinked hydrogel demonstrated lower thermostability due to the weaker crosslinking degree. In vitro, all silk fibroin hydrogels supported the growth of human umbilical vein endothelial cells, as the cell viability of hydrogels without chemical agents was relatively higher. This study provides insights into the formation process of silk fibroin hydrogels and optimizes their design strategy for biomedical applications.

Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models.

N-terminal processing by methionine aminopeptidases (MetAP) is a crucial step in the maturation of proteins during protein biosynthesis. Small-molecule inhibitors of MetAP2 have antiangiogenic and antitumoral activity. Herein, we characterize the structurally novel MetAP2 inhibitor M8891. M8891 is a potent, selective, reversible small-molecule inhibitor blocking the growth of human endothelial cells and differentially inhibiting cancer cell growth. A CRISPR genome-wide screen identified the tumor suppressor p53 and MetAP1/MetAP2 as determinants of resistance and sensitivity to pharmacologic MetAP2 inhibition. A newly identified substrate of MetAP2, translation elongation factor 1-alpha-1 (EF1a-1), served as a pharmacodynamic biomarker to follow target inhibition in cell and mouse studies. Robust angiogenesis and tumor growth inhibition was observed with M8891 monotherapy. In combination with VEGF receptor inhibitors, tumor stasis and regression occurred in patient-derived xenograft renal cell carcinoma models, particularly those that were p53 wild-type, had Von Hippel-Landau gene (VHL) loss-of-function mutations, and a mid/high MetAP1/2 expression score.

Chirality-Dependent Angiogenic Activity of MoS2 Quantum Dots toward Regulatable Tissue Regeneration.

Despite great advances in understanding the biological behaviors of chiral materials, the effect of chirality-configured nanoparticles on tissue regeneration-related biological processes remains poorly understood. Herein, the chirality of MoS2 quantum dots (QDs) is tailored by functionalization with l-/d-penicillamine, and the profound chiral effects of MoS2 QDs on cellular activities, angiogenesis, and tissue regeneration are thoroughly investigated. Specifically, d-MoS2 QDs show a positive effect in promoting the growth, proliferation, and migration of human umbilical vein endothelial cells. The expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and fibroblast growth factor (FGF) in d-MoS2 QDs group is substantially up-regulated, resulting in enhanced tube formation activity. This distinct phenomenon is largely due to the higher internalization efficiency of d-MoS2 QDs than l-MoS2 QDs and chirality-dependent nano-bio interactions. In vivo angiogenic assay shows the expression level of angiogenic markersin newly-formed skin tissues of d-MoS2 QDs group is higher than that in l-MoS2 QDs group, leading to an accelerated re-epithelialization and improved skin regeneration. The findings of chirality-dependent angiogenesis activity of MoS2 QDs provide new insights into the biological activity of MoS2 nanomaterials, which also opens up a new path to the rational design of chiral nanomaterials for tissue regeneration application.

Small diameter expanded polytetrafluoroethylene vascular graft with differentiated inner and outer biomacromolecules for collaborative endothelialization, anti-thrombogenicity and anti-inflammation

Without differentiated inner and outer biological function, expanded polytetrafluoroethylene (ePTFE) small-diameter (<6 mm) artificial blood vessels would fail in vivo due to foreign body rejection, thrombosis, and hyperplasia. In order to synergistically promote endothelialization, anti-thrombogenicity, and anti-inflammatory function, we modified the inner and outer surface of ePTFE, respectively, by grafting functional biomolecules, such as heparin and epigallocatechin gallate (EGCG), into the inner surface and polyethyleneimine and rapamycin into the outer surface via layer-by-layer self-assembly. Fourier-transform infrared spectroscopy showed the successful incorporation of EGCG, heparin, and rapamycin. The collaborative release profile of heparin and rapamycin lasted for 42 days, respectively. The inner surface promoted human umbilical vein endothelial cells (HUVECs) adhesion and growth and that the outer surface inhibited smooth muscle cells growth and proliferation. The modified ePTFE effectively regulated the differentiation behavior of RAW264.7, inhibited the expression of proinflammatory mediator TNF-α, and up-regulated the expression of anti-inflammatory genes Arg1 and Tgfb-1. The ex vivo circulation results indicated that the occlusions and total thrombus weight of modified ePTFE was much lower than that of the thrombus formed on the ePTFE, presenting good anti-thrombogenic properties. Hence, the straightforward yet efficient synergistic surface functionalization approach presented a potential resolution for the prospective clinical application of small-diameter ePTFE blood vessel grafts.

Curcumin-loaded porous scaffold: an anti-angiogenic approach to inhibit endochondral ossification

Bone marrow stem cells (BMSCs) are recognized for their robust proliferative capabilities and multidirectional differentiation potential. Ectopic endochondral ossification of BMSC-generated cartilage in subcutaneous environments is a concern associated with vascularization. Hence, devising a reliable strategy to inhibit vascularization is crucial. In this study, an anti-angiogenic drug, curcumin (Cur), was encapsulated into gelatin to create a porous Cur/Gelatin scaffold, with the aim of inhibiting vascular invasion and preventing endochondral ossification of BMSC-regenerated cartilage. In vitro wound healing tests demonstrated that a 30 μM Cur solution could inhibit the migration and growth of human umbilical vein endothelial cells without impeding BMSCs migration and growth. Compared to the gelatin scaffold, our findings verified that the Cur/Gelatin scaffold significantly inhibited vascular invasion after being subcutaneously implanted into rabbits for 12 weeks, as evidenced by gross observation and immunofluorescence CD31 staining. Moreover, both the porous gelatin and Cur/Gelatin scaffolds were populated with BMSCs and underwent in vitro chondrogenic cultivation to produce cartilage, followed by subcutaneous implantation in rabbits for 12 weeks. Histological examinations (including HE, Safranin-O/Fast Green, toluidine blue, and immunohistochemical COL II staining) revealed that the BMSC-generated cartilage in the gelatin group exhibited prominent endochondral ossification. In contrast, the BMSC-generated cartilage in the Cur/Gelatin group maintained cartilage features, such as cartilage matrix and lacunar structure. This study suggests that Cur-loaded scaffolds offer a reliable platform to inhibit endochondral ossification of BMSC-generated cartilage.

EDIL3 and VEGF Synergistically Affect Angiogenesis in Endothelial Cells.

Angiogenesis is one of the histologically predominant characteristics of psoriasis. Vascular endothelial growth factor (VEGF) and epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) have critical effects on angiogenesis. Both these proteins are vital proangiogenic factors in tumor occurrence and progression; however, the relationship between EDIL3 and VEGF with psoriasis remains unclear. We aimed to elucidate the role of EDIL3 and VEGF and the involved mechanisms in psoriasis-associated angiogenesis. EDIL3 and VEGF expression in cutaneous tissue was determined by immunohistochemical assay. The effects of EDIL3 on VEGF, VEGFR2, and the growth, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were analyzed by Western blotting assay, cell counting kit-8 assay, Transwell assay, and Matrigel tube formation assay. EDIL3 and VEGF levels in psoriatic lesions significantly increased as compared to those in normal individuals and showed a positive relationship with the Psoriasis Area and Severity Index. The downregulation of EDIL3 decreased VEGF and VEGFR2 expression in HUVECs. Moreover, the decreased expression of EDIL3 and VEGF reduced the growth, invasion, and tube formation abilities of HUVECs, while EDIL3 resistance to VEGF and VEGFR2 was restored by using the EDIL3 recombinant protein. These results suggest that psoriasis is also characterized by EDIL3 and VEGF-mediated angiogenesis. Thus, EDIL3 and VEGF could serve as novel targets for treating psoriasis.

Woven Vascular Stent-Grafts with Surface Modification of Silk Fibroin-Based Paclitaxel/Metformin Microspheres.

In-stent restenosis caused by tumor ingrowth increases the risk of secondary surgery for patients with abdominal aortic aneurysms (AAA) because conventional vascular stent grafts suffer from mechanical fatigue, thrombosis, and endothelial hyperplasia. For that, we report a woven vascular stent-graft with robust mechanical properties, biocompatibility, and drug delivery functions to inhibit thrombosis and the growth of AAA. Paclitaxel (PTX)/metformin (MET)-loaded silk fibroin (SF) microspheres were self-assembly synthesized by emulsification-precipitation technology and layer-by-layer coated on the surface of a woven stent via electrostatic bonding. The woven vascular stent-graft before and after coating drug-loaded membranes were characterized and analyzed systematically. The results show that small-sized drug-loaded microspheres increased the specific surface area and promoted the dissolution/release of drugs. The stent-grafts with drug-loaded membranes exhibited a slow drug-release profile more for than 70 h and low water permeability at 158.33 ± 17.56 mL/cm2·min. The combination of PTX and MET inhibited the growth of human umbilical vein endothelial cells. Therefore, it was possible to generate dual-drug-loaded woven vascular stent-grafts to achieve the more effective treatment of AAA.

Antiangiogenic Pterocarpan and Flavonoid Constituents of Erythrina lysistemon.

The roots of Erythrina lysistemon, growing in Egypt, yielded 24 flavonoid compounds, including 17 pterocarpans, two isoflavanones, one flavanone, two isoflavans, one 2-arylbenzofuran, and an isoflava-3-ene. Nine pterocarpans have not been reported previously (7-9, 11-14, 19, and 20), and 11 are reported here for the first time from this species. Structures were established using HRESIMS, NMR, and circular dichroism techniques. Selected compounds were tested for their ability to block the growth of human retinal endothelial cells and antiangiogenic activity in vitro. The isoflavonoids 5 and 6, and the pterocarpans 1, 2, 4, 20, and 22 demonstrated selective antiproliferative activities on endothelial cells compared to a nonendothelial cell type, with concentration-dependent antiangiogenic effects in vitro against HRECs, a cell type relevant to neovascular eye diseases.

An Aligned Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Scaffold Fixed with Fibronectin to Enhance the Attachment and Growth of Human Endothelial Progenitor Cells

An Aligned Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Scaffold Fixed with Fibronectin to Enhance the Attachment and Growth of Human Endothelial Progenitor Cells

Expanded polytetrafluoroethylene/poly(3-hydroxybutyrate) (ePTFE/PHB) triboelectric nanogenerators and their potential applications as self-powered and sensing vascular grafts

Being able to detect or monitor the onset of thrombosis, recurrent stenosis, or other vascular disorders in newly transplanted vascular grafts will be very beneficial for patients who received the artificial blood vessel through bypass surgeries. The inherent advantages of triboelectric nanogenerators (TENGs) in self-powered signal monitoring presents a feasible solution. In this study, a double-layer TENG intended for self-powered and real-time sensing of vascular graft applications was constructed using two biocompatible materials commonly used in tissue engineering. In particular, an electrospun poly(3-hydroxybutyrate) (PHB) membrane as a positive tribomaterial was combined with an expanded polytetrafluoroethylene (ePTFE) membrane, a strong negative tribomaterial, to construct an ePTFE/PHB TENG. While possessing power generation, charging capacities, and operation stability, the ePTFE/PHB TENG was capable of supporting the growth of human umbilical vein endothelial cells (HUVECs) and monitoring changing hemodynamic conditions. Although many challenges remain and necessary future developments are needed, this study demonstrated the feasibility of a self-powered and sensing TENG vascular graft.

Computer-aided patterning of PCL microspheres to build modular scaffolds featuring improved strength and neovascularized tissue integration

In the past decade, modular scaffolds prepared by assembling biocompatible and biodegradable building blocks (e.g. microspheres) have found promising applications in tissue engineering (TE) towards the repair/regeneration of damaged and impaired tissues. Nevertheless, to date this approach has failed to be transferred to the clinic due to technological limitations regarding microspheres patterning, a crucial issue for the control of scaffold strength, vascularization and integration in vivo. In this work, we propose a robust and reliable approach to address this issue through the fabrication of polycaprolactone (PCL) microsphere-based scaffolds with in-silico designed microarchitectures and high compression moduli. The scaffold fabrication technique consists of four main steps, starting with the manufacture of uniform PCL microspheres by fluidic emulsion technique. In the second step, patterned polydimethylsiloxane (PDMS) moulds were prepared by soft lithography. Then, layers of 500 µm PCL microspheres with geometrically inspired patterns were obtained by casting the microspheres onto PDMS moulds followed by their thermal sintering. Finally, three-dimensional porous scaffolds were built by the alignment, stacking and sintering of multiple (up to six) layers. The so prepared scaffolds showed excellent morphological and microstructural fidelity with respect to the in-silico models, and mechanical compression properties suitable for load bearing TE applications. Designed porosity and pore size features enabled in vitro human endothelial cells adhesion and growth as well as tissue integration and blood vessels invasion in vivo. Our results highlighted the strong impact of spatial patterning of microspheres on modular scaffolds response, and pay the way about the possibility to fabricate in silico-designed structures featuring biomimetic composition and architectures for specific TE purposes.

Retraction Statement.

Retraction Statement.

Heterogeneous nuclear ribonucleoprotein U-actin complex derived from extracellular vesicles facilitates proliferation and migration of human coronary artery endothelial cells by promoting RNA polymerase II transcription

ABSTRACT Coronary artery disease (CAD) represents a fatal public threat. The involvement of extracellular vesicles (EVs) in CAD has been documented. This study explored the regulation of embryonic stem cells (ESCs)-derived EVs-hnRNPU-actin complex in human coronary artery endothelial cell (HCAEC) growth. Firstly, in vitro HCAEC hypoxia models were established. EVs were extracted from ESCs by ultracentrifugation. HCAECs were treated with EVs and si-VEGF for 24 h under hypoxia, followed by assessment of cell proliferation, apoptosis, migration, and tube formation. Uptake of EVs by HCAECs was testified. Additionally, hnRNPU, VEGF, and RNA Pol II levels were determined using Western blotting and CHIP assays. Interaction between hnRNPU and actin was evaluated by Co-immunoprecipitation assay. HCAEC viability and proliferation were lowered, apoptosis was enhanced, wound fusion was decreased, and the number of tubular capillary structures was reduced under hypoxia, whereas ESC-EVs treatment counteracted these effects. Moreover, EVs transferred hnRNPU into HCAECs. EVs-hnRNPU-actin complex increased RNA Pol II level on the VEGF gene promoter and promoted VEGF expression in HCAECs. Inhibition of hnRNPU or VEGF both annulled the promotion of EVs on HCAEC growth. Collectively, ESC-EVs-hnRNPU-actin increased RNA Pol II phosphorylation and VEGF expression, thus promoting HCAEC growth.

A Biomimetic Composite Bilayer Dressing Composed of Alginate and Fibroin for Enhancing Full-Thickness Wound Healing.

Full-thickness skin wound dressings are critically important for acute cutaneous wound healing. In this study, a bilayer sheet originating from biological macromolecules, mimicking skin hierarchy structure is developed. This sheet is composed of a steady silk fibroin (SF)/sodium alginate (SA) composite scaffold as the bottom regenerative layer and a SA film as the protective top layer. Scanning electron microscope analysis revealed the thickness of the top layer is ≈25µm and is tightly adhered to the composite scaffold layer with interconnected pores (≈150µm). The bilayer sheets are displayed suitable water uptake capacity and high stability in water. The mass retention percentage of the bilayer sheets is ≈50% during three weeks of PBS degradation in vitro. The tensile strength of the bilayer sheets is significantly increased from 13.41±3.75kPa (single scaffold) to 59.81±5.98kPa. The composite scaffolds are more conducive to the growth and proliferation of human dermal microvascular endothelial cells. The experiment results in vivo are demonstrated superior and faster epithelialization and dermal regeneration in the wound treated with bilayer sheets because the sheets are accelerated wound closure, reduced the inflammatory response, and promoted protein synthesis in the extracellular matrix and blood vessel ingrowth.

Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions.

The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to regulate endothelial cell functions and angiogenesis. In this study, the functions of YAP and TAZ in human endothelial progenitor cells (EPCs) were investigated by a loss-of-function study using CRISPR/Cas9-mediated gene knockdown (KD). Depletion of either YAP or TAZ reduced EPC survival and impaired many of their critical functions, including migration, invasion, vessel-formation, and expression of pro-angiogenic genes. Notably, TAZ-KD EPCs exhibited more severe phenotypes in comparison to YAP-KD EPCs. Moreover, the conditioned medium derived from TAZ-KD EPCs reduced the survivability of human lung cancer cells and increased their sensitivity to chemotherapeutic agents. The overexpression of either wild-type or constitutively active TAZ rescued the impaired phenotypes of TAZ-KD EPCs and restored the expression of pro-angiogenic genes in those EPCs. In summary, we demonstrate the crucial role of Hippo signaling components, YAP and TAZ, in controlling several aspects of EPC functions that can potentially be used as a drug target to enhance EPC functions in patients.