The effect of human osteoblasts on proliferation and neo-vessel formation of human umbilical vein endothelial cells in a long-term 3D co-culture on polyurethane scaffolds

Hofmann, Alexander; Ritz, Ulrike; Verrier, Sophie; Eglin, David; Alini, Mauro; Fuchs, Sabine; Kirkpatrick, Charles James; Rommens, Pol Maria

doi:10.1016/j.biomaterials.2008.07.024

Cited by 176 publications

(151 citation statements)

References 53 publications

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“…[4][5][6][7][8]53,77,78 Previous studies have investigated whether prevascularizing 3D constructs in vitro would eradicate this limitation, through the coculture of endothelial stem cells with MSCs [40][41][42][43][79][80][81][82][83] or osteoblasts, 45,84,85 and found that prevascular networks are formed both in vitro and in vivo. Our previous study previously found that rudimentary vessels were formed in vitro when both MSCs and HUVECs were added to the already formed cartilage template.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

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In vitro bone regeneration strategies that prime mesenchymal stem cells (MSCs) with chondrogenic factors, to mimic aspects of the endochondral ossification process, have been shown to promote mineralization and vascularization by MSCs both in vitro and when implanted in vivo. However, these approaches required the use of osteogenic supplements, namely dexamethasone, ascorbic acid, and b-glycerophosphate, none of which are endogenous mediators of bone formation in vivo. Rather MSCs, endothelial progenitor cells, and chondrocytes all reside in proximity within the cartilage template and might paracrineally regulate osteogenic differentiation. Thus, this study tests the hypothesis that an in vitro bone regeneration approach that mimics the cellular niche existing during endochondral ossification, through coculture of MSCs, endothelial cells, and chondrocytes, will obviate the need for extraneous osteogenic supplements and provide an alternative strategy to elicit osteogenic differentiation of MSCs and mineral production. The specific objectives of this study were to (1) mimic the cellular niche existing during endochondral ossification and (2) investigate whether osteogenic differentiation could be induced without the use of any external growth factors. To test the hypothesis, we evaluated the mineralization and vessel formation potential of (a) a novel methodology involving both chondrogenic priming and the coculture of human umbilical vein endothelial cells (HUVECs) and MSCs compared with (b) chondrogenic priming of MSCs alone, (c) addition of HUVECs to chondrogenically primed MSC aggregates, (d-f) the same experimental groups cultured in the presence of osteogenic supplements and (g) a noncoculture group cultured in the presence of osteogenic growth factors alone. Biochemical (DNA, alkaline phosphatase [ALP], calcium, CD31 + , vascular endothelial growth factor [VEGF]), histological (alcian blue, alizarin red), and immunohistological (CD31 + ) analyses were conducted to investigate osteogenic differentiation and vascularization at various time points (1, 2, and 3 weeks). The coculture methodology enhanced both osteogenesis and vasculogenesis compared with osteogenic differentiation alone, whereas osteogenic supplements inhibited the osteogenesis and vascularization (ALP, calcium, and VEGF) induced through coculture alone. Taken together, these results suggest that chondrogenic and vascular priming can obviate the need for osteogenic supplements to induce osteogenesis of human MSCs in vitro, while allowing for the formation of rudimentary vessels.

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Section: Discussionmentioning

confidence: 99%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

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“…Contact coculture of ECs with MSCs can induce vascularization both in vitro and in vivo [20,[45][46][47], and thus is a promising solution to controlled vascularization enhancement in therapeutic needs. Here, we uncovered the underlying communication mechanism in MSCs-ECs coculture at molecular level by scrutinizing their transcriptional profiles separately.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

LiJunxiang

MaYing

TengRuifang

et al. 2015

Stem Cells and Development

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Mesenchymal stem cells (MSCs) show great promise in blood vessel restoration and vascularization enhancement in many therapeutic situations. Typically, the co-implantation of MSCs with vascular endothelial cells (ECs) is effective for the induction of functional vascularization in vivo, indicating its potential applications in regenerative medicine. The effects of MSCs-ECs-induced vascularization can be modeled in vitro, providing simplified models for understanding their underlying communication. In this article, a contact coculture model in vitro and an RNA-seq approach were employed to reveal the active crosstalk between MSCs and ECs within a short time period at both morphological and transcriptional levels. The RNA-seq results suggested that angiogenic genes were significantly induced upon coculture, and this prevascularization commitment might require the NF-kB signaling. NF-kB blocking and interleukin (IL) neutralization experiments demonstrated that MSCs potentially secreted IL factors including IL1b and IL6 to modulate NF-kB signaling and downstream chemokines during coculture. Conversely, RNA-seq results indicated that the MSCs were regulated by the coculture environment to a smooth muscle commitment within this short period, which largely induced myocardin, the myogenic co-transcriptional factor. These findings demonstrate the mutual molecular mechanism of MSCs-ECs-induced prevascularization commitment in a quick response.

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“…Several strategies have been developed to promote vascularization of engineered tissue following implantation, including biomaterial and scaffold modification, use of growth factors, and the use of co-culture systems [104]. The use of angiogenic cells in co-culture has also been explored, and endothelial lineages [26•, [105][106][107][108] have been incorporated into engineered tissue constructs to promote vessel formation. These angiogenic cells spontaneously form prevascular networks in vitro and anastomose rapidly following implantation, leading to perfusion of the construct.…”

Section: Bone Metastatic Diseasementioning

confidence: 99%

Human Bone Xenografts: from Preclinical Testing for Regenerative Medicine to Modeling of Diseases

Chong

Bao

et al. 2016

Curr Mol Bio Rep

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Xenografting involves the transplantation of human tissue or cells into animal models and is an important tool for regenerative medicine research. Implantation of engineered human bone tissues into animal models, for example, is performed in preclinical evaluations of product safety and efficacy. With the advent of improved experimental methodologies, these models are further being exploited to interrogate molecular mechanisms and physiological interactions in vivo. In parallel to these developments, patient-derived xenograft murine models of cancer are increasingly being studied for various applications in cancer research and therapy; it follows that xenograft models in tissue engineering may be adapted for such approaches. In this review, we first discuss the development of human bone xenograft models to recapitulate physiological states in regenerative medicine. Subsequently, we discuss the use of these techniques for applications in modeling pathological states in skeletal oncology, namely, hematopoietic malignancies, bone metastatic disease, and primary bone malignancy.

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The effect of human osteoblasts on proliferation and neo-vessel formation of human umbilical vein endothelial cells in a long-term 3D co-culture on polyurethane scaffolds

Cited by 176 publications

References 53 publications

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

Human Bone Xenografts: from Preclinical Testing for Regenerative Medicine to Modeling of Diseases

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