ArticleStem cell research & therapy2018
Delivery of VEGFA in bone marrow stromal cells seeded in copolymer scaffold enhances angiogenesis, but is inadequate for osteogenesis as compared with the dual delivery of VEGFA and BMP2 in a subcutaneous mouse model.
Article in Stem cell research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- The Use of Osteo-Inductive 3D-Printed Scaffolds Covered with a Pleiotrophin Peptide for Bone Defects: An In Vivo Experimental Study.Bioengineering (Basel, Switzerland) · 2026Article
- Hyaluronic acid-coated Poly(L-lactide-co-1,3-trimethylene carbonate) modulate early cellular-scaffold interactions and osteogenic potential: a comprehensiveFrontiers in bioengineering and biotechnology · 2026Article
- Osteogenic Differentiation in Chitosan-Based Scaffolds via P28 and VEGF Delivery.Molecules (Basel, Switzerland) · 2025Article
- Preclinical Evaluation and Advancements in Vascularized Bone Tissue Engineering.Biomimetics (Basel, Switzerland) · 2025Review
- Evolution in Bone Tissue Regeneration: From Grafts to Innovative Biomaterials.International journal of molecular sciences · 2025Review
- Research progress of gene therapy combined with tissue engineering to promote bone regeneration.APL bioengineering · 2024Review
- Cascaded controlled delivering growth factors to build vascularized and osteogenic microenvironment for bone regeneration.Materials today. Bio · 2024Article
- Extracellular vesicles: From bone development to regenerative orthopedics.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Bone regeneration of mouse critical-sized calvarial defects with human mesenchymal stem cell sheets co-expressing BMP2 and VEGF.Journal of dental sciences · 2023Article
- Extracellular vesicles derived from human bone marrow mesenchymal stem cells protect rats against acute myocardial infarction-induced heart failure.Cell and tissue research · 2022Article
- Immune-instructive copolymer scaffolds using plant-derived nanoparticles to promote bone regeneration.Inflammation and regeneration · 2022Article
- Synthetic materials in craniofacial regenerative medicine: A comprehensive overview.Frontiers in bioengineering and biotechnology · 2022Review
- Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing.International journal of biological sciences · 2022Article
- Design of 3D Scaffolds for Hard Tissue Engineering: From Apatites to Silicon Mesoporous Materials.Pharmaceutics · 2021Review
- Spatiotemporal blood vessel specification at the osteogenesis and angiogenesis interface of biomimetic nanofiber-enabled bone tissue engineering.Biomaterials · 2021Article
- EGFL6 regulates angiogenesis and osteogenesis in distraction osteogenesis via Wnt/β-catenin signaling.Stem cell research & therapy · 2021Article
- [Research progress ofZhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2021Review
- Angiogenic property of silk fibroin scaffolds with adipose-derived stem cells on chick chorioallantoic membrane.Royal Society open science · 2021Article
- Accelerated Bone Regeneration by Adrenomedullin 2 Through Improving the Coupling of Osteogenesis and Angiogenesis via β-Catenin Signaling.Frontiers in cell and developmental biology · 2021Article
- Effects of ergosteroside combined risedronate on fracture healing and BMP-2, BMP-7 and VEGF expression in rats.Acta cirurgica brasileira · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn bone tissue engineering (BTE), extensive research into vascular endothelial growth factor A (VEGFA)-mediated angiogenesis has yielded inconsistent results. The aim of this study was to investigate the influence on angio- and osteogenesis of adenoviral-mediated delivery of VEGFA alone or in combination with bone morphogenetic protein 2 (BMP2) in bone marrow stromal cells (BMSC) seeded onto a recently developed poly(LLA-co-CL) scaffold.
methodsHuman BMSC were engineered to express VEGFA alone or in combination with BMP2 and seeded onto poly(LLA-co-CL) scaffolds. Changes in angiogenic and osteogenic gene and protein levels were examined by quantitative reverse-transcription polymerase chain reaction (RT-PCR), PCR array, and alkaline phosphatase assay. An in vivo subcutaneous mouse model was used to investigate the effect on angio- and osteogenesis of VEGFA alone or in combination with BMP2, using microcomputed tomography (μCT), histology, immunohistochemistry, and immunofluorescence.
resultsCombined delivery of a lower ratio (1:3) of VEGFA and BMP2 (ad-BMP2 + VEGFA) led to upregulation of osteogenic and angiogenic genes in vitro at 3 and 14 days, compared with mono-delivery of VEGFA (ad-VEGFA) and other controls. In vivo, in a subcutaneous mouse model, both ad-VEGFA and ad-BMP2 + VEGFA scaffold explants exhibited increased angiogenesis at 2 weeks. Enhanced angiogenesis was largely related to the recruitment and differentiation of mouse progenitor cells to the endothelial lineage and, to a lesser extent, to endothelial differentiation of the implanted BMSC. μCT and histological analyses revealed enhanced de novo bone formation only in the ad-BMP2 + VEGFA group, corresponding at the molecular level to the upregulation of genes related to osteogenesis, such as ALPL, RUNX2, and SPP1.
conclusionsAlthough BMSC expressing VEGFA alone or in combination with BMP2 significantly induced angiogenesis, VEGFA alone failed to demonstrate osteogenic activity both in vitro and in vivo. These results not only call into question the use of VEGFA alone in bone regeneration, but also highlight the importance in BTE of appropriately formulated combined delivery of VEGFA and BMP2.
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