Injectable Bone Tissue Engineering Using Expanded Mesenchymal Stem Cells

Yamada, Yoichi; Nakamura, Sayaka; Ito, Kenji; Umemura, Eri; Hara, Kenji; Nagasaka, Tetsuro; Abe, Akihiro; Baba, Shigeaki; Furuichi, Yasushi; Izumi, Yuichi; Klein, Ophir D.; Wakabayashi, Toshihiko

doi:10.1002/stem.1300

Cited by 83 publications

(85 citation statements)

References 38 publications

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“…The main concept involves three elements: stem cells, scaffolds, and growth factors. The mesenchymal stem cells (MSCs) found within the periodontal tissues are multipotent cells that can replicate as undifferentiated cells and possess the capacity of multilineage differentiation [7–9]. They are more recent and highly regarded because of their potential for use in cell-based therapy for systemic diseases.…”

Section: Introductionmentioning

confidence: 99%

Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three‐Dimensional Woven‐Fabric Scaffold for Periodontitis

Baba

Yamada

Komuro

et al. 2016

Stem Cells International

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Regenerative medicine is emerging as a promising option, but the potential of autologous stem cells has not been investigated well in clinical settings of periodontal treatment. In this clinical study, we evaluated the safety and efficacy of a new regenerative therapy based on the surgical implantation of autologous mesenchymal stem cells (MSCs) with a biodegradable three-dimensional (3D) woven-fabric composite scaffold and platelet-rich plasma (PRP). Ten patients with periodontitis, who required a surgical procedure for intrabony defects, were enrolled in phase I/II trial. Once MSCs were implanted in each periodontal intrabony defect, the patients were monitored during 36 months for a medical exam including laboratory tests of blood and urine samples, changes in clinical attachment level, pocket depth, and linear bone growth (LBG). All three parameters improved significantly during the entire follow-up period (p < 0.0001), leading to an average LBG of 4.7 mm after 36 months. Clinical mobility measured by Periotest showed a decreasing trend after the surgery. No clinical safety problems attributable to the investigational MSCs were identified. This clinical trial suggests that the stem cell therapy using MSCs-PRP/3D woven-fabric composite scaffold may constitute a novel safe and effective regenerative treatment option for periodontitis.

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Section: Introductionmentioning

confidence: 99%

Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three‐Dimensional Woven‐Fabric Scaffold for Periodontitis

Baba

Yamada

Komuro

et al. 2016

Stem Cells International

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“…An applicable cell source with an abundant supply, easy accessibility, and no immunogenic reaction with osteoplastic potential is required for the successful cell-based treatment of bone (Yamada et al, 2013). ADMSCs can differentiate into adipogenic, osteogenic, chondrogenic, myogenic lineages, and osteoblasts (Mizuno et al, 2002;Zuk et al, 2002;Semyari et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

hBMP-7 induces the differentiation of adipose-derived mesenchymal stem cells into osteoblast-like cells

et al. 2016

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ABSTRACT. The aim of this study was to investigate the differentiation potential of adipose-derived mesenchymal stem cells (ADMSCs) into osteoblasts by human bone morphogenetic protein-7 (hBMP-7) induction. ADMSCs were isolated from the subcutaneous adipose tissue of a rabbit, and then transfected with the pcDNA3.1 vector alone and pcDNA3.1-hBMP-7 (hBMP-7), respectively. Untransfected ADMSCs were used as the control group. After transfection, the morphology and green fluorescent protein (GFP) fluorescence intensity of ADMSCs were observed by fluorescent microscopy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the growth of ADMSCs at 1, 3, and 5 days, respectively. Transmission electron microscopy was performed to observe the ultrastructural morphology of ADMSCs. In addition, ADMSCs were stained with quinalizarin and toluidine blue to reflect the content of osteoblasts and chondrocytes, respectively. Finally, the expression of collagen I and osteocalcin in ADMSCs was detected by western blot. ADMSCs were successfully isolated. Obvious GFP fluorescence and high expression of hBMP-7 demonstrated the successful transfection of hBMP-7. Specific morphological characters with a metabolically active ultrastructure were exhibited on the ADMSCs transfected with hBMP-7. In addition, the growth rate of ADMSCs transfected with hBMP-7 was significantly higher than that of the cells in the vector and control groups. Successfully induced osteoblast-like cells were identified by an obvious erythrine area and high expression of collagen I and osteocalcin in ADMSCs transfected with hBMP-7. Thus, ADMSCs can be successfully differentiated into osteoblast-like cells by hBMP-7 induction in vitro.

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“…Tissue engineered bones have been widely documented as one of the most promising strategies for treating large bone defects (18,19). However, the classical tissue engineering strategy is associated with some drawbacks, such as prolonged duration, high costs, critical technique requirements and ethical issues, with limit the generalization and applications in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

The Osteogenetic Efficacy of Goat Bone Marrow-Enriched Self-Assembly Peptide/Demineralized Bone MatrixIn VitroandIn Vivo

Hou²,

Deng³

et al. 2015

Tissue Engineering Part A

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In clinical practice, the prolonged duration, high cost, critical technique requirements, and ethical issues make the classical construction method of tissue-engineered bones difficult to apply widely. The major essentials in tissue engineering strategies include seed cells, growth factors, and scaffolds. This study aimed to incorporate these factors in a rapid and cost-effective manner. A self-assembly peptide/demineralized bone matrix (SAP/DBM) composite was artificially established and used for bone marrow enrichment via a selective cell retention approach. Then, goat mesenchymal stem cells (gMSCs) were seeded onto the SAP/DBM or DBM. The proliferation status of gMSCs in different scaffolds was analyzed, and the osteogenetic efficacy was evaluated after osteogenic induction. Bilateral critical-sized femoral defects (20-mm in length) were created in goats, and then the defects were implanted with the postenriched composite or DBM. Then, bone scan imaging, micro-computed tomography (CT) analysis and histological examination were performed to assess the reparative effects of the different implants. Compared with the DBM scaffolds, the growth of gMSCs in the postenriched SAP/DBM composite was faster and the expression levels of the osteo-specific genes (i.e., alkaline phosphatase, osteocalcin, osteopontin, and runt-related transcription factor 2) were significantly higher after 14 days of osteogenic induction. More importantly, the postenriched SAP/DBM composite significantly enhanced bone metabolic activity in the defect area compared with DBM at 2 and 4 weeks postoperation. Moreover, bone reconstruction was complete in marrow-enriched SAP/DBM composite, but not in the DBM. In addition, all of the osteo-related parameters, including the ratio of bone volume to total bone volume, bone mineral density, new trabecular number, and new trabecular thickness, were significantly higher in the marrow-enriched SAP/DBM than those in the DBM. These results indicated that the SAP/DBM composite held great potential for clinical applications; immediate implantation after marrow enrichment could be a new and effective strategy for treating bone defect.

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Injectable Bone Tissue Engineering Using Expanded Mesenchymal Stem Cells

Cited by 83 publications

References 38 publications

Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three‐Dimensional Woven‐Fabric Scaffold for Periodontitis

Phase I/II Trial of Autologous Bone Marrow Stem Cell Transplantation with a Three‐Dimensional Woven‐Fabric Scaffold for Periodontitis

hBMP-7 induces the differentiation of adipose-derived mesenchymal stem cells into osteoblast-like cells

The Osteogenetic Efficacy of Goat Bone Marrow-Enriched Self-Assembly Peptide/Demineralized Bone MatrixIn VitroandIn Vivo

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