Stromal Cell–Derived Factor‐1 Significantly Induces Proliferation, Migration, and Collagen Type I Expression in a Human Periodontal Ligament Stem Cell Subpopulation

Du, Liqing; Yang, Pishan; Ge, Shaohua

doi:10.1902/jop.2011.110201

Cited by 70 publications

(74 citation statements)

References 45 publications

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“…Until now, there are no strong indications that SDF-1a could recruit enough cells to fully replace MSC seeding in a mouse subcutaneous bone formation model [43]. Further evaluation of the direct effects of SDF1a on MSC performance with respect to proliferation and (trans)differentiation, as has been suggested by other studies [41,42,44,45], could explain some of the results.…”

Section: Figmentioning

confidence: 89%

CXCL12/Stromal-Cell-Derived Factor-1 Effectively Replaces Endothelial Progenitor Cells to Induce Vascularized Ectopic Bone

Eman

Hoorntje

Öner

et al. 2014

Stem Cells and Development

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Bone defect healing is highly dependent on the simultaneous stimulation of osteogenesis and vascularization. In bone regenerative strategies, combined seeding of multipotent stromal cells (MSCs) and endothelial progenitor cells (EPCs) proves their mutual stimulatory effects. Here, we investigated whether stromal-cell-derived factor1a (SDF-1a) stimulates vascularization by EPCs and whether SDF-1a could replace seeded cells in ectopic bone formation. Late EPCs of goat origin were characterized for their endothelial phenotype and showed to be responsive to SDF-1a in in vitro migration assays. Subsequently, subcutaneous implantation of Matrigel plugs that contained both EPCs and SDF-1a showed more tubule formation than constructs containing either EPCs or SDF-1a. Addition of either EPCs or SDF-1a to MSC-based constructs showed even more elaborate vascular networks after 1 week in vivo, with SDF-1a/MSC-laden groups showing more prominent interconnected networks than EPC/MSC-laden groups. The presence of abundant mouse-specific CD31/PECAM expression in these constructs confirmed ingrowth of murine vessels and discriminated between angiogenesis and vessel networks formed by seeded goat cells. Importantly, implantation of EPC/MSC or SDF-1a/MSC constructs resulted in indistinguishable ectopic bone formation. In both groups, bone onset was apparent at week 3 of implantation. Taken together, we demonstrated that SDF-1a stimulated the migration of EPCs in vitro and vascularization in vivo. Further, SDF-1a addition was as effective as EPCs in inducing the formation of vascularized ectopic bone based on MSC-seeded constructs, suggesting a cell-replacement role for SDF-1a. These results hold promise for the design of larger centimeter-scale, cell-free vascular bone grafts.

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Section: Figmentioning

confidence: 89%

CXCL12/Stromal-Cell-Derived Factor-1 Effectively Replaces Endothelial Progenitor Cells to Induce Vascularized Ectopic Bone

Eman

Hoorntje

Öner

et al. 2014

Stem Cells and Development

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“…All soluble factors were reconstituted in the manufacturer's recommended solutions, and then diluted to experimental concentrations (Table 1) in serum-free media. Soluble factor doses were selected based on the literature 22,[25][26][27]35,[37][38][39] and on preliminary screening experiments that assayed at least six dose levels per factor (data not shown). Immobilization experiments were carried out in serum-free, nonsupplemented media.…”

Section: Scaffold Culture Conditionsmentioning

confidence: 99%

“…The growth factor bFGF has shown the capacity to improve tenocyte proliferation and collagen synthesis, 22 MSC chemotaxis, 31 and the tenogenic differentiation of MSCs both in two-dimensional (2D) 32 and 3D 33 culture systems. SDF-1a has been implicated as a potent chemoattractant of MSCs during wound healing, 29,34 but recently has shown the ability to improve ligament stem cell proliferation and migration 35 as well as functional tendon regeneration in a rat Achilles model. 36 GDF-5 has been shown to increase both tenocyte and adiposederived stem cell proliferation and expression of tendon markers 37-39 as well as the formation of neo-tendinous tissue in a rat ectopic model.…”

Section: Introductionmentioning

confidence: 99%

Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds

Caliari

Harley

2013

Tissue Engineering Part A

102

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Biomolecular environments encountered in vivo are complex and dynamic, with combinations of biomolecules presented in both freely diffusible (liquid-phase) and sequestered (bound to the extracellular matrix) states. Strategies for integrating multiple biomolecular signals into a biomimetic scaffold provide a platform to simultaneously control multiple cell activities, such as motility, proliferation, phenotype, and regenerative potential. Here we describe an investigation elucidating the influence of the dose and mode of presentation (soluble, sequestered) of five biomolecules (stromal cell-derived factor 1a , platelet-derived growth factor BB [PDGF-BB], insulin-like growth factor 1 [IGF-1], basic fibroblast growth factor [bFGF], and growth/ differentiation factor 5 [GDF-5]) on the recruitment, proliferation, collagen synthesis, and genomic stability of equine tenocytes within an anisotropic collagen-GAG scaffold for tendon regeneration applications. Critically, we found that single factors led to a dose-dependent trade-off between driving tenocyte proliferation (PDGF-BB, IGF-1) versus maintenance of a tenocyte phenotype (GDF-5, bFGF). We identified supplementation schemes using factor pairs (IGF-1, GDF-5) to rescue the tenocyte phenotype and gene expression profiles while simultaneously driving proliferation. These results suggest coincident application of multi-biomolecule cocktails has a significant value in regenerative medicine applications where control of cell proliferation and phenotype are required. Finally, we demonstrated an immobilization strategy that allows efficient sequestration of bioactive levels of these factors within the scaffold network. We showed sequestration can lead to a greater sustained bioactivity than soluble supplementation, making this approach particularly amenable to in vivo translation where diffusive loss is a concern and continuous biomolecule supplementation is not feasible.

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“…37 PDLSCs were plated at 8 × 10 3 cells per well in 96-well plates and cultured in α-MEM supplemented with 5% fetal calf serum, 100 mM L-ascorbate-2-phosphate, 1 mM sodium pyruvate, 50 µg/mL streptomycin, 50 U/mL penicillin G, 2 mM L-glutamine, 0.1 µM dexamethasone (Mayne Pharma, Mulgrave, Australia), and 1.8 mM inorganic phosphate (KH 2 PO 4 ; BDH Chemicals, Poole, UK) for 4 weeks, with the medium changed twice weekly. Mineral deposit formation was identified by Alizarin Red staining (Sigma-Aldrich).…”

Section: Multipotent Differentiation Of Single Colony-derived Pdlscsmentioning

confidence: 99%

“…37 PDLSCs were plated in α-MEM supplemented with 5% fetal calf serum, 100 mM L-ascorbate-2-phosphate, 1 mM sodium pyruvate, 50 µg/mL streptomycin, 50 U/mL penicillin G, 2 mM L-glutamine, 0.1 µM dexamethasone, and 60 µM indomethacin (Sigma-Aldrich), and cultured for 4 weeks, with the medium changed twice weekly. Formation of lipid-laden fat cells was determined by Oil Red O staining (MP Biomedicals, Solon, OH).…”

Section: Multipotent Differentiation Of Single Colony-derived Pdlscsmentioning

confidence: 99%

Bone repair by periodontal ligament stem cell-seeded nanohydroxyapatite-chitosan scaffold

Ge¹,

Zhao²,

Wang³

et al. 2012

IJN

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Background: A nanohydroxyapatite-coated chitosan scaffold has been developed in recent years, but the effect of this composite scaffold on the viability and differentiation of periodontal ligament stem cells (PDLSCs) and bone repair is still unknown. This study explored the behavior of PDLSCs on a new nanohydroxyapatite-coated genipin-chitosan conjunction scaffold (HGCCS) in vitro as compared with an uncoated genipin-chitosan framework, and evaluated the effect of PDLSC-seeded HGCCS on bone repair in vivo. Methods: Human PDLSCs were cultured and identified, seeded on a HGCCS and on a genipinchitosan framework, and assessed by scanning electron microscopy, confocal laser scanning microscopy, MTT, alkaline phosphatase activity, and quantitative real-time polymerase chain reaction at different time intervals. Moreover, PDLSC-seeded scaffolds were used in a rat calvarial defect model, and new bone formation was assessed by hematoxylin and eosin staining at 12 weeks postoperatively. Results: PDLSCs were clonogenic and positive for STRO-1. They had the capacity to undergo osteogenic and adipogenic differentiation in vitro. When seeded on HGCCS, PDLSCs exhibited significantly greater viability, alkaline phosphatase activity, and upregulated the bone-related markers, bone sialoprotein, osteopontin, and osteocalcin to a greater extent compared with PDLSCs seeded on the genipin-chitosan framework. The use of PDLSC-seeded HGCCS promoted calvarial bone repair. Conclusion: This study demonstrates the potential of HGCCS combined with PDLSCs as a promising tool for bone regeneration.

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Stromal Cell–Derived Factor‐1 Significantly Induces Proliferation, Migration, and Collagen Type I Expression in a Human Periodontal Ligament Stem Cell Subpopulation

Abstract: SDF-1 may have the potential of promoting periodontal tissue regeneration by the mechanism of guiding PDLSCs to destructive periodontal tissue, promoting their activation and proliferation and influencing the differentiation of these stem cells.

Cited by 70 publications

References 45 publications

CXCL12/Stromal-Cell-Derived Factor-1 Effectively Replaces Endothelial Progenitor Cells to Induce Vascularized Ectopic Bone

CXCL12/Stromal-Cell-Derived Factor-1 Effectively Replaces Endothelial Progenitor Cells to Induce Vascularized Ectopic Bone

Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds

Bone repair by periodontal ligament stem cell-seeded nanohydroxyapatite-chitosan scaffold

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