Patient-Derived Human Induced Pluripotent Stem Cells From Gingival Fibroblasts Composited With Defined Nanohydroxyapatite/Chitosan/Gelatin Porous Scaffolds as Potential Bone Graft Substitutes

Ji, Jun; Tong, Xin; Huang, Xiaofeng; Zhang, Junfeng; Qin, Haiyan; Hu, Qingang

doi:10.5966/sctm.2015-0139

Cited by 46 publications

(51 citation statements)

References 58 publications

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“…; Ji et al . ), and could be induced by different cytokines to form cartilage and bone (Rutherford et al . ; Tang et al .…”

Section: Introductionmentioning

confidence: 99%

“…As an important component of the periodontium, the gingival tissue could be obtained from patients undergoing teeth extraction, thus the collection of gingival tissue was by convenience. It has been reported that HGFs have the potential of multi-directional differentiation Ji et al 2016), and could be induced by different cytokines to form cartilage and bone (Rutherford et al 2002;Tang et al 2011). However, the question about whether HGFs could be induced by pro-angiogenic factors to differentiate into endothelial-like cells is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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Human gingival fibroblasts induced and differentiated into vascular endothelial‐like cells

et al. 2016

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A novel method for repair of vascular disease, mechanical damage, and tissue rebuilding is urgently required. Vascular endothelial cells (VECs) play an essential role in vascular rebuilding and vasotransplantation. In the present study, human gingival fibroblasts (HGFs) were cultured and induced into endothelial-like cells in vitro in order to confirm that HGFs with stem cell properties possessed the potential for differentiation into endothelial-like cells. The epithelium was extracted from normal human gingiva consisting of epithelium and connective tissue, which was isolated from patients. The identification of HGFs and induced endothelial-like cells were confirmed by flow cytometry, reverse transcription polymerase chain reaction (RT-PCR), immunocytochemical stain (ICS), and immunofluorescence stain (ISA). The morphology of human gingival fibroblasts with 8 ng/mL VEGF165 induced for different periods of days were observed by inverted microscope. Before induction, flow cytometry analysis showed that HGFs were positive for vimentin, but negative for CD31. RT-PCR, ICS, and ISA showed vimentin, S100A4, α-SMA, collagen III, and S100A4 were specifically expressed in these fibroblast cells. After induction, ICS showed induced vascular endothelial-like cells were positive for CD34 and CD31; ISA showed cells induced were positive for vWF and E-cadherin; RT-PCR results demonstrated that tie2 was specifically expressed in the cells induced. Flow cytometry analysis of the transformation efficiency from HGFs to endothelial-like cells. In conclusion, we found that HGFs possessed capacity for being induced and differentiated into vessel endothelial-like cells with typical and specific morphological, ultrastructural, and immunological characters of endothelial-like cells by induction with VEGF.

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“…; Ji et al . ), and could be induced by different cytokines to form cartilage and bone (Rutherford et al . ; Tang et al .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human gingival fibroblasts induced and differentiated into vascular endothelial‐like cells

et al. 2016

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“…hiPSCs have been differentiated into OBs on 2D plastic and 3D CaP scaffolds7891011 and produced dense bone matrix on 3D decellurized bone scaffolds in a perfusion bioreactor12. OCs have been generated from hiPSCs on 2D plastic and on mineralized substrates by embryonic body (EB) formation13 and by co-culturing with stromal cells14.…”

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confidence: 99%

Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials

Jeon

Panicker

et al. 2016

Sci Rep

132

107

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Bone substitutes can be designed to replicate physiological structure and function by creating a microenvironment that supports crosstalk between bone and immune cells found in the native tissue, specifically osteoblasts and osteoclasts. Human induced pluripotent stem cells (hiPSC) represent a powerful tool for bone regeneration because they are a source of patient-specific cells that can differentiate into all specialized cell types residing in bone. We show that osteoblasts and osteoclasts can be differentiated from hiPSC-mesenchymal stem cells and macrophages when co-cultured on hydroxyapatite-coated poly(lactic-co-glycolic acid)/poly(L-lactic acid) (HA–PLGA/PLLA) scaffolds. Both cell types seeded on the PLGA/PLLA especially with 5% w/v HA recapitulated the tissue remodeling process of human bone via coupling signals coordinating osteoblast and osteoclast activity and finely tuned expression of inflammatory molecules, resulting in accelerated in vitro bone formation. Following subcutaneous implantation in rodents, co-cultured hiPSC-MSC/-macrophage on such scaffolds showed mature bone-like tissue formation. These findings suggest the importance of coupling matrix remodeling through osteoblastic matrix deposition and osteoclastic tissue resorption and immunomodulation for tissue development.

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“…The use of GFP-labelled hESC-OPs would be extremely useful in noninvasive imaging of bone regeneration within three-dimensional (3D) in vitro scaffolds and in vivo animal models. Recently, several studies have produced bone-like matrix by seeding human PSCs on different 3D scaffolds [40–43] and using perfusion bioreactors [44, 45]. Jeon et al used a biomimetic approach to regenerate bone by 3D coculture of human PSC-derived osteoblasts and osteoclasts within a synthetic scaffolds [46].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Osteogenic Potential of Green Fluorescent Protein Labelled Human Embryonic Stem Cell‐Derived Osteoprogenitors

Islam

Sriram

et al. 2016

Stem Cells International

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Cellular therapy using stem cells in bone regeneration has gained increasing interest. Various studies suggest the clinical utility of osteoprogenitors-like mesenchymal stem cells in bone regeneration. However, limited availability of mesenchymal stem cells and conflicting evidence on their therapeutic efficacy limit their clinical application. Human embryonic stem cells (hESCs) are potentially an unlimited source of healthy and functional osteoprogenitors (OPs) that could be utilized for bone regenerative applications. However, limited ability to track hESC-derived progenies in vivo greatly hinders translational studies. Hence, in this study, we aimed to establish hESC-derived OPs (hESC-OPs) expressing green fluorescent protein (GFP) and to investigate their osteogenic differentiation potential in vitro. We fluorescently labelled H9-hESCs using a plasmid vector encoding GFP. The GFP-expressing hESCs were differentiated into hESC-OPs. The hESC-OPsGFP+ stably expressed high levels of GFP, CD73, CD90, and CD105. They possessed osteogenic differentiation potential in vitro as demonstrated by increased expression of COL1A1, RUNX2, OSTERIX, and OPG transcripts and mineralized nodules positive for Alizarin Red and immunocytochemical expression of osteocalcin, alkaline phosphatase, and collagen-I. In conclusion, we have demonstrated that fluorescently labelled hESC-OPs can maintain their GFP expression for the long term and their potential for osteogenic differentiation in vitro. In future, these fluorescently labelled hESC-OPs could be used for noninvasive assessment of bone regeneration, safety, and therapeutic efficacy.

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Patient-Derived Human Induced Pluripotent Stem Cells From Gingival Fibroblasts Composited With Defined Nanohydroxyapatite/Chitosan/Gelatin Porous Scaffolds as Potential Bone Graft Substitutes

Cited by 46 publications

References 58 publications

Human gingival fibroblasts induced and differentiated into vascular endothelial‐like cells

Human gingival fibroblasts induced and differentiated into vascular endothelial‐like cells

Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials

In Vitro Osteogenic Potential of Green Fluorescent Protein Labelled Human Embryonic Stem Cell‐Derived Osteoprogenitors

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