Application of Induced Pluripotent Stem (iPS) Cells in Periodontal Tissue Regeneration

Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts 02111, USA.
Journal of Cellular Physiology (Impact Factor: 3.84). 01/2011; 226(1):150-7. DOI: 10.1002/jcp.22316
Source: PubMed


Tissue engineering provides a new paradigm for periodontal tissue regeneration in which proper stem cells and effective cellular factors are very important. The objective of this study was, for the first time, to investigate the capabilities and advantages of periodontal tissue regeneration using induced pluripotent stem (iPS) cells and enamel matrix derivatives (EMD). In this study the effect of EMD gel on iPS cells in vitro was first determined, and then tissue engineering technique was performed to repair periodontal defects in three groups: silk scaffold only; silk scaffold + EMD; and silk scaffold + EMD + iPS cells. EMD greatly enhanced the mRNA expression of Runx2 but inhibited the mRNA expression of OC and mineralization nodule formation in vitro. Transplantation of iPS cells showed higher expression levels of OC, Osx, and Runx2 genes, both 12 and 24 days postsurgery. At 24 days postsurgery in the iPS cell group, histological analysis showed much more new alveolar bone and cementum formation with regenerated periodontal ligament between them. The results showed the commitment role that EMD contributes in mesenchymal progenitors to early cells in the osteogenic lineage. iPS cells combined with EMD provide a valuable tool for periodontal tissue engineering, by promoting the formation of new cementum, alveolar bone, and normal periodontal ligament.

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Available from: Cesar Sommer, Oct 02, 2015
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    • "To date, 4 studies have investigated the potential utility of iPSCs in various dental applications, including periodontal regeneration (Duan et al. 2011) and tooth development and regeneration (Otsu et al. 2012; Wen et al. 2012; Cai et al. 2013). Duan et al. (2011) investigated the potential of human iPSCs to regenerate periodontal tissues when implanted into a surgically created periodontal fenestration defect. The addition of iPSCs resulted in significantly more alveolar bone formation , cementum, and PDL regeneration in mice that received iPSCs in combination with a silk scaffold and enamel matrix derivatives (EMDs), as compared with control mice that received either the silk scaffold and EMDs or the silk scaffold alone. "
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    ABSTRACT: Induced pluripotent stem cells (iPSCs) are the newest member of a growing list of stem cell populations that hold great potential for use in cell-based treatment approaches in the dental field. This review summarizes the dental tissues that have successfully been utilized to generate iPSC lines, as well as the potential uses of iPSCs for tissue regeneration in different dental applications. While iPSCs display great promise in a number of dental applications, there are safety concerns with these cells that need to be addressed before they can be used in clinical settings. This review outlines some of the apprehensions to the use of iPSCs clinically, and it details approaches that are being employed to ensure the safety and efficacy of these cells. One of the major approaches being investigated is the differentiation of iPSCs prior to use in patients. iPSCs have successfully been differentiated into a wide range of cells and tissue types. This review focuses on 2 differentiation approaches-the differentiation of iPSCs into mesenchymal stem cells and the differentiation of iPSCs into osteoprogenitor cells. Both these resulting populations of cells are particularly relevant to the dental field. © International & American Associations for Dental Research 2015.
    Journal of dental research 08/2015; DOI:10.1177/0022034515599769 · 4.14 Impact Factor
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    • "In a study by Duan et al, iPS cells from mice, delivered by means of a silk scaffold in a combination with enamel derived factors, were used to induce regeneration of periodontal tissues in a murine model of periodontal defect (Duan et al., 2011). After treatment, histomorphometric analysis revealed that significantly greater amounts of new bone and cementum formation were evident when defects were treated with the combination of cells, scaffold, and enamel derived factors rather than scaffold alone or a combination of scaffold and growth factors, suggesting that transplantation of iPS cells can enhance periodontal regeneration (Duan et al., 2011). "
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    ABSTRACT: Periodontal diseases are highly prevalent and are linked to several systemic diseases.The goal of periodontal treatment is to halt the progression of the disease and regenerate the damaged tissue. However, achieving complete and functional periodontal regeneration is challenging because the periodontium is a complex apparatus composed of different tissues, including bone, cementum, and periodontal ligament. Stem cell-based regenerative therapy may represent an effective therapeutic tool for periodontal regeneration due to their plasticity and ability to differentiate into different cell lineages. This review presents and critically analyzesthe available information on stem cell-based therapyfor the regeneration of periodontal tissues and suggests new avenues for the development of more effective therapeutic protocols. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Cellular Physiology 06/2015; DOI:10.1002/jcp.25067 · 3.84 Impact Factor
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    • "It is well-known that stem cells (human embryonic stem cells, mesenchymal stem cells derived from various human tissue, and induced pluripotent stem cells) have diverse lineage differentiation potential and self-renewal capacity1,2,3,4,5. These cells have been studied extensively for applications in the field of regenerative medicine. "
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    ABSTRACT: Objectives The purpose of this study was to investigate the neurogenic differentiation of human dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and stem cells from apical papilla (SCAP). Materials and Methods After induction of neurogenic differentiation using commercial differentiation medium, expression levels of neural markers, microtubule-associated protein 2 (MAP2), class III β-tubulin, and glial fibrillary acidic protein (GFAP) were identified using reverse transcriptase polymerase chain reaction (PCR), real-time PCR, and immunocytochemistry. Results The induced cells showed neuron-like morphologies, similar to axons, dendrites, and perikaryons, which are composed of neurons in DPSCs, PDLSCs, and SCAP. The mRNA levels of neuronal markers tended to increase in differentiated cells. The expression of MAP2 and β-tubulin III also increased at the protein level in differentiation groups, even though GFAP was not detected via immunocytochemistry. Conclusion Human dental stem cells including DPSCs, PDLSCs, and SCAP may have neurogenic differentiation capability in vitro. The presented data support the use of human dental stem cells as a possible alternative source of stem cells for therapeutic utility in the treatment of neurological diseases.
    08/2014; 40(4):173-80. DOI:10.5125/jkaoms.2014.40.4.173
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