The effect of the co-immobilization of human osteoprogenitors and endothelial cells within alginate microspheres on mineralization in a bone defect

Grellier, Maritie; Granja, Pedro L.; Fricain, Jean-Christophe; Bidarra, Sílvia J.; Renard, Martine; Bareille, Reine; Bourget, Chantal; Amédée, Joëlle; Barbosa, Mário A.

doi:10.1016/j.biomaterials.2009.02.033

Cited by 199 publications

(187 citation statements)

References 36 publications

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“…In contrast to our suggested mechanism of paracrine signaling, several other groups failed to show osteogenic enhancement when MSCs were cultured in the CM of ECs [40], instead suggesting direct cell-cell contact via gap junction communication was required to mediate the osteogenic enhancement effect [21,41]. These groups, however, used mature human ECs in coculture with osteoblast-like cells, which although they have shown promise in generating a prevascularized network [15,23] and/or enhancing osteogenesis [20,21,[40][41][42][43], their biological phenotype depends upon the site of the endothelium from which they were harvested from [44].…”

Section: Discussionmentioning

confidence: 69%

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

et al. 2012

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Umbilical cord blood‐derived endothelial colony‐forming cells (UCB‐ECFC) show utility in neovascularization, but their contribution to osteogenesis has not been defined. Cocultures of UCB‐ECFC with human fetal‐mesenchymal stem cells (hfMSC) resulted in earlier induction of alkaline phosphatase (ALP) (Day 7 vs. 10) and increased mineralization (1.9×; p < .001) compared to hfMSC monocultures. This effect was mediated through soluble factors in ECFC‐conditioned media, leading to 1.8–2.2× higher ALP levels and a 1.4–1.5× increase in calcium deposition (p < .01) in a dose‐dependent manner. Transcriptomic and protein array studies demonstrated high basal levels of osteogenic (BMPs and TGF‐βs) and angiogenic (VEGF and angiopoietins) regulators. Comparison of defined UCB and adult peripheral blood ECFC showed higher osteogenic and angiogenic gene expression in UCB‐ECFC. Subcutaneous implantation of UCB‐ECFC with hfMSC in immunodeficient mice resulted in the formation of chimeric human vessels, with a 2.2‐fold increase in host neovascularization compared to hfMSC‐only implants (p = .001). We conclude that this study shows that UCB‐ECFC have potential in therapeutic angiogenesis and osteogenic applications in conjunction with MSC. We speculate that UCB‐ECFC play an important role in skeletal and vascular development during perinatal development but less so in later life when expression of key osteogenesis and angiogenesis genes in ECFC is lower. Stem Cells2012;30:1911–1924

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Section: Discussionmentioning

confidence: 69%

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

et al. 2012

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“…In the current study, in addition to reducing the diameter of the alginate microspheres to < 500 mm, RGD-coupled alginate hydrogel was also utilized to provide a suitable chemical microenvironment for dental MSCs by presenting ligands that specifically bind to cell receptors. 44,45,47,48,49 Cell viability analysis and MTT assays showed that up to 80% of encapsulated cells were viable while immobilized in these new alginate microspheres, which suggests a favorable inward flux of nutrients and sufficient levels of oxygen to the cell cluster within the alginate. Thus, we observed very high cell viability and metabolic activity after up to 2 weeks of culturing.…”

Section: Discussionmentioning

confidence: 96%

Bone Regeneration Potential of Stem Cells Derived from Periodontal Ligament or Gingival Tissue Sources Encapsulated in RGD-Modified Alginate Scaffold

Moshaverinia

Chen

et al. 2013

Tissue Engineering Part A

117

131

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Mesenchymal stem cells (MSCs) provide an advantageous alternative therapeutic option for bone regeneration in comparison to current treatment modalities. However, delivering MSCs to the defect site while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated bone regeneration. Here, we tested the bone regeneration capacity of periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) encapsulated in a novel RGD-(arginine-glycine-aspartic acid tripeptide) coupled alginate microencapsulation system in vitro and in vivo. Five-millimeter-diameter critical-size calvarial defects were created in immunocompromised mice and PDLSCs and GMSCs encapsulated in RGD-modified alginate microspheres were transplanted into the defect sites. New bone formation was assessed using microcomputed tomography and histological analyses 8 weeks after transplantation. Results confirmed that our microencapsulation system significantly enhanced MSC viability and osteogenic differentiation in vitro compared with non-RGD-containing alginate hydrogel microspheres with larger diameters. Results confirmed that PDLSCs were able to repair the calvarial defects by promoting the formation of mineralized tissue, while GMSCs showed significantly lower osteogenic differentiation capability. Further, results revealed that RGD-coupled alginate scaffold facilitated the differentiation of oral MSCs toward an osteoblast lineage in vitro and in vivo, as assessed by expression of osteogenic markers Runx2, ALP, and osteocalcin. In conclusion, these results for the first time demonstrated that MSCs derived from orofacial tissue encapsulated in RGD-modified alginate scaffold show promise for craniofacial bone regeneration. This treatment modality has many potential dental and orthopedic applications.

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“…Several approaches have been proposed to improve the neovascularisation process of engineered tissues during the past decade, including the use of endothelial cells or endothelial progenitor cells (Grellier et al, 2009;Rivron et al, 2008;Rouwkema et al, 2006), strategies based on the natural interaction of the different cell types during the process of bone regeneration using co-culture systems (Fuchs et al, 2007;Kaigler et al, 2003) or additional treatment or coupling of tissue engineered constructs with proangiogenic growth factors or morphogens (Dohle et al, 2011;Dohle et al, 2010;Zisch et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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

Dohle

Bischoff²,

Böse³

et al. 2014

eCM

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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 new blood vessels. The aim of this study was to investigate if macrophages might positively influence the formation of microvessel-like structures via inflammatory mechanisms in a co-culture system consisting of human outgrowth endothelial cells (OECs) and primary osteoblasts. Treatment of co-cultures with macrophages (induced from THP-1) resulted in a higher number of microvessel-like structures formed by OECs compared to the co-culture. This change correlated with a significantly higher concentration of the proangiogenic VEGF in cell culture supernatants of triple-cultures and was accompanied by an increase in the expression of different proinflammatory cytokines, such as IL-6, IL-8 and TNFα. In addition, the expression of E-selectin and ICAM-1, adhesion molecules which are strongly involved in the interaction between leukocytes and endothelial cells during the process of inflammation was also found to be higher in triple-cultures compared to the double co-cultures, documenting an ongoing proinflammatory stimulus. These results raise the possibility of actively using pro-inflammatory stimuli in a tissue engineering context to accelerate healing mechanisms.

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The effect of the co-immobilization of human osteoprogenitors and endothelial cells within alginate microspheres on mineralization in a bone defect

Cited by 199 publications

References 36 publications

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

Bone Regeneration Potential of Stem Cells Derived from Periodontal Ligament or Gingival Tissue Sources Encapsulated in RGD-Modified Alginate Scaffold

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

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