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  • Use of Stem Cells in Dental Implants and Enamel Regenerative TherapiesUpadhyay RK*

    Department of Zoology, Deen Dayal Upadhyay Gorakhpur University, India*Corresponding author: Upadhyay RK, Department of Zoology, DDU Gorakhpur University, Gorakhpur 273009, Uttar Pradesh, India, Tel:9838448495; E-mail: rkupadhya@yahoo.com

    Received date: Oct 08, 2015; Accepted date: Jan 15, 2015; Published date: Jan 18, 2015

    Abstract

    Present review article emphasizes use of variousstem cell types, biological scaffold materials, genes andfactors essentially required in woundhealing, transplantation and regeneration of toothimplants. All recent developments in tooth engineeringused for successful regeneration of tooth, inductionof enamel and formation of dentin complexes arehighlighted. In addition, genes, factors and mineralsrequired in vascularization and maintenance ofmicroenvironment for responsiveness to cells are alsoelucidated as most attractive candidates for regenerationtherapy. Present review also elucidates use of stable anddurable biodegradable polymer scaffolds materials andcementum/periodontal-ligament complex formation.There is a need to widen the horizon of bio-rootengineering technology for successful repairing of toothinjuries and replacement of fractured or traumatizedtooth. For this purpose, use of implantation ofcultured stem cells, adhesion factors and biomaterials canprovide stable attachment of dental implants. This reviewalso sketch upon need of newer technologies and moreadhesive biocompatible biomaterials for successful dentalimplants and enamel regenerative therapies.

    Keywords: Stem cells; Dental cell implants;Enamel matrix derivatives; Tooth regeneration; Enamel matrixderivatives; Adhesion factors and biomaterials

    Abbreviations:PDL: Periodontal Ligament; PDLSCs: Periodontal Ligament

    Stem Cells; EMD: Enamel Matrix Derivative; DPSC: Dental PulpStromal Cells; DMCs: Dermal Multipotent Cells; MSC:Mesenchymal Stem Cells; FBS: Fetal Bovine Serum; MDO:Mandibular Distraction in Osteogenesis; MSCT: MesenchymalStem Cell Transplantations; DBM: Demineralized Bone Matrix;DFDBA: Human Demineralized Freeze-Dried Bone Allograft;BMP: Bone Morphogenetic Proteins; BMMSCs: Bone MarrowMesenchymal Stem Cells

    IntroductionPeriodontal diseases and tooth decay and enamel

    destruction including periodontal ligament (PDL), cementum,and bone are a major causes of tooth loss in adults. This is amajor public-health problem in pediatric and adults groupsworldwide. PDL is a specialized connective tissue that connectscementum and alveolar bone to maintain and support teeth insitu and preserve tissue homoeostasis. Recent advancementsin implantation technology of dentally derived stem cells orhuman PDL stem cells, led to significant progress in the field oftooth regeneration [1]. PDLSCs in defined culture conditionsdifferentiate into cementoblasts, adipocytes, and collagen-forming cells. These cells when transplanted generate acementum/PDL-like structure that contribute periodontaltissue repair. Today many advanced technologies are in use tosupport tooth enamel development and regeneration in vitroas well as in vivo. For successful tooth regeneration culturedstem cells, cementing adhesives and biological scaffoldmaterials are used. More often, for transplantation purpose,stem cells are derived from an easily accessible tissue sourceand expanded ex vivo. These stem cell types are promisingtherapeutic tools which are used for reconstruction of enameltissues that are destroyed due to periodontal diseases. In lastthree decades tissue engineering has emerged as a promisingalternative approach to find solutions and clinical treatmentsfor restoration of soft tissue defects mainly related to enameland dental pulp. There have been made numerous rapid andexciting developments in tissue engineering technology whichsuccessfully regenerate and form a fully functional tooth inanimal models, from a bioengineered tooth germ cell. In thesemethods bone-forming stem cells, new osteoinductivebiomaterials, and growth factors are used. For growth anddevelopment of tissue engineered tooth, stem cells areimplanted into different tissues that need suitable growingenvironment in vivo [2] (Figure 1). These have revolutionizedthe toot regeneration therapy and assisted the clinicians andenable them to conduct successful clinical trials for findingappropriate solutions of decayed and defective tooth [3](Figure 2). Guided tissue regeneration is used forreconstructive osseous surgery [4].

    Review Article

    iMedPub Journalshttp://www.imedpub.com/

    Insights in Stem CellsVol.2 No.1:9

    2016

    Copyright iMedPub | This article is available from: http://stemcells.imedpub.com/ 1

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  • Figure 1 showing integration of stem cell therapy, tissueengineering and biomaterial technology in regenerativemedicine for clinical management and therapeutics basedon academic researches, industry and hospitals

    Figure 2 Showing use of regeneration therapies for varioustooth defects

    Table 1 Different types of tooth related problems and solutions based on available technology and methods

    Problem Orthodontic reason/defect Solution Reference

    Erupted tooth Expressed cytokeratin 14, dentin matrix protein-1, vascularendothelial growth factor, and osteopontin

    DBC-fibrin glue-PRF composite wasautografted back into the original alveolarsockets

    Yang, et al. [27]

    Structural erosion orfragile tooth

    Induced morphological changes occur due to increasedalkaline phosphatase (ALP) activity, runt-related transcriptionfactor 2 (RUNX2), osteocalcin (OCN), and bone sialoprotein(BSP) expression in PDLSCs

    Correction of microRNAs (miRNAs) inhuman periodontal ligament stemcells(PDLSCs

    Wei, et al. (2015)

    Periodontal trauma Structural and functional integrity of the periodontiumfollowing periodontal trauma such as orthodontic toothmovement

    High mobility group box protein-1 (HMGB1) Wolf, et al. (2015)

    Traumatic injuries Loss of structural/compositional sensitivity of enamel tissue A mixed population of bone marrow-derived autologous stem andprogenitor cells are seeded onto -tricalcium phosphate (-TCP)

    Rajan, et al. (50)

    Osteoporosis Osteocalcium disorder, elemental loss and pulp and enameldestruction due to loss of calcium and phosphates

    FasL pathways mediated differentiation ofERK and GSK-3-catenin pathway

    Ming, et al. (2014)

    Osteoporosis intermittent mechanical strain (IMS) Promoted osteogenic differentiation ofOVX BMSCs by activating Runt-relatedtranscription factor 2

    Zhang, et al. (2015)

    Tumor progression andmetastasis/ Tumorblood vessels

    Upregulation of vascular endothelial growth factor (VEGF)and VEGF receptor 2

    Antitumor therapy, radioactive and laserbased destruction

    Ohmura-Kakutani, etal. (2014)

    Craniofacial problems Implantation of stem cells Use of cultured stem cells from sourcetissue and organ from which stem cells canbe derived

    Mohanty, et al. (2015)

    Fibrodysplasiaossificans progressiva

    Low level of protein expression in receptor cells Bone morphogenetic protein (BMP)receptor ALK2, R206H are used

    Fujimoto, et al. (2014)

    Bone and tooth pain Limited capacity to induce bone formation Restoration by using rhBMP-2, DFDBAand EMD

    Intini, et al. [33]

    Demineralization embryonic tooth morphogenesis and promotes continuoustooth development

    beta-catenin signaling Liu, et al. (2010)

    Faulty and defectivetooth arrangment

    Organization of predentin/dentin, enamel, and cementum Mineralization after implantation Lechguer, et al. (37)

    Hard tissue formation Post-natal mesenchymal stromal cells (MSCs) includingbone marrow stromal cells (BMSCs) and periodontalligament fibroblasts (PDLFs).

    Straumann Bone Ceramic coated withStraumann Emdogain

    Mrozik, et al. (16)

    Insights in Stem Cells

    Vol.2 No.1:9

    2016

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  • Loss of dental pulp andnon clinical damage

    FGF molecules are able to maintain epithelial Tbx1expression during odontogenesis, Expression of Tbx1in dental epithelium of FGF receptor 2b(-/-)

    Mesenchyme-derived signals Mitsiadis, et al. (34)

    Odontogenesis Forced expression of Gli1, a major transcription factor in Shhsignaling

    Amelogenin and ameloblastin. Takahashi, et al.(35,57)

    Odontogenesis Sonic hedgehog (Shh) in enamel knot Use of Sonic hedgehog (Shh) Takahashi, et al.(35,57)

    Low osteogenicdifferentiation

    miR-26a potentially targeted on GSK3 and Smad1 toregulate Wnt and BMP signaling pathway

    MicroRNAs (miRNAs) used as importantregulators of stem cell

    Su, et al. (2015)

    Orthodontic toothmovement (OTM)

    induces local inflammation in periodontium OTM induced a significant elevation of type1 T helper cell (Th1) cytokines tumornecrosis factor- (TNF-) and interferon-(IFN-) around periodontal tissue in WT

    Yan, et al. (2015)

    Untimely enamel loss Obstruction in muscle formation and decreasing scar tissuecontraction

    Scaffold-free cells and mesenchymal stemcells scaffold

    Zhou, et al. (2015)

    Loss of osteogeniccapability

    Mitogen-activated protein kinase (MAPK) signaling pathways Use of BMMSCs and PBMSCs cells,regenerative medicine

    Zheng, et al. (63)

    Enamel cell and dentalpulp infection

    von Willebrand factor (vWF) and CD31 immunofluorescentstaining, different energy densities of infrared LED on the cellviability

    Vascular endothelial growth factor (VEGF)and basic fibroblast growth factor (bFGF)are used for pulp and enamel repairing

    Feng, et al. (2015)

    Fragile deciduous teeth Enamel cell destruction and low calc