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Basabrain MS, Zaeneldin A, Bijle MN, Zhang C. Dental stem cell sphere formation and potential for neural regeneration: A scoping review. Heliyon 2024; 10:e40262. [PMID: 39619582 PMCID: PMC11605411 DOI: 10.1016/j.heliyon.2024.e40262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 10/26/2024] [Accepted: 11/07/2024] [Indexed: 01/31/2025] Open
Abstract
Background Dental stem cells with neurosphere-forming abilities are a promising cell source for the treatment of neural diseases and injuries. This scoping review aimed to systematically map the existing literature on dental sphere formation assays and their characteristics associated with neural regeneration potential. Methods The Web of Science, EMBASE, SCOPUS, and PubMed databases were systematically searched for in vitro, animal, and clinical studies and reviews focusing on stem cells isolated from the oral cavity, subsequently cultured as spheres with neural regeneration potential. Data were extracted and evidence was synthesized according to the predetermined variables in the registered protocol. Results A total of 35 articles (31 in vitro, 1 combined in vitro and in vivo, and 3 reviews) were included. The predominant method utilized for sphere formation was low-attachment culture. Spheres were characterized using assessment of neural marker expression via confocal microscopy, immunohistochemistry, RT-qPCR, or western blotting. Overall, the synthesized results indicate a lack of in vivo studies investigating the utility of dental neurospheres for neural regeneration, with dental pulp stem cells being the most investigated for their neural regenerative potential. Conclusion Dental stem cell spheres demonstrate significant potential for neural regeneration. Several assays and characterizations have been performed to characterized the mechanisms underlying dental sphere formation. Furthermore, in vivo studies are imperative to deduce the neural regenerative potential of stem cells in complex biological environments.
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Affiliation(s)
- Mohammed S. Basabrain
- Restorative Dental Sciences, Faculty of Dentistry, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ahmed Zaeneldin
- Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, China
| | - Mohammed Nadeem Bijle
- Paediatric Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
| | - Chengfei Zhang
- Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, China
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2
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Mohebichamkhorami F, Niknam Z, Zali H, Mostafavi E. Therapeutic Potential of Oral-Derived Mesenchymal Stem Cells in Retinal Repair. Stem Cell Rev Rep 2023; 19:2709-2723. [PMID: 37733198 DOI: 10.1007/s12015-023-10626-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2023] [Indexed: 09/22/2023]
Abstract
The retina has restricted regeneration ability to recover injured cell layer because of reduced production of neurotrophic factors and increased inhibitory molecules against axon regrowth. A diseased retina could be regenerated by repopulating the damaged tissue with functional cell sources like mesenchymal stem cells (MSCs). The cells are able to release neurotrophic factors (NFs) to boost axonal regeneration and cell maintenance. In the current study, we comprehensively explore the potential of various types of stem cells (SCs) from oral cavity as promising therapeutic options in retinal regeneration. The oral MSCs derived from cranial neural crest cells (CNCCs) which explains their broad neural differentiation potential and secret rich NFs. They are comprised of dental pulp SCs (DPSCs), SCs from exfoliated deciduous teeth (SHED), SCs from apical papilla (SCAP), periodontal ligament-derived SCs (PDLSCs), gingival MSCs (GMSCs), and dental follicle SCs (DFSCs). The Oral MSCs are becoming a promising source of cells for cell-free or cell-based therapeutic approach to recover degenerated retinal. These cells have various mechanisms of action in retinal regeneration including cell replacement and the paracrine effect. It was demonstrated that they have more neuroprotective and neurotrophic effects on retinal cells than immediate replacement of injured cells in retina. This could be the reason that their therapeutic effects would be weakened over time. It can be concluded that neuronal and retinal regeneration through these cells is most likely due to their NFs that dramatically suppress oxidative stress, inflammation, and apoptosis. Although, oral MSCs are attractive therapeutic options for retinal injuries, more preclinical and clinical investigations are required.
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Affiliation(s)
- Fariba Mohebichamkhorami
- Department of Food Science & Technology, University of California, Davis, CA, 95616, USA
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Niknam
- Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Hakimeh Zali
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Ebrahim Mostafavi
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA.
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
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Yang C, Du XY, Luo W. Clinical application prospects and transformation value of dental follicle stem cells in oral and neurological diseases. World J Stem Cells 2023; 15:136-149. [PMID: 37181000 PMCID: PMC10173814 DOI: 10.4252/wjsc.v15.i4.136] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/18/2023] [Accepted: 03/21/2023] [Indexed: 04/26/2023] Open
Abstract
Since dental pulp stem cells (DPSCs) were first reported, six types of dental SCs (DSCs) have been isolated and identified. DSCs originating from the craniofacial neural crest exhibit dental-like tissue differentiation potential and neuro-ectodermal features. As a member of DSCs, dental follicle SCs (DFSCs) are the only cell type obtained at the early developing stage of the tooth prior to eruption. Dental follicle tissue has the distinct advantage of large tissue volume compared with other dental tissues, which is a prerequisite for obtaining a sufficient number of cells to meet the needs of clinical applications. Furthermore, DFSCs exhibit a significantly higher cell proliferation rate, higher colony-formation capacity, and more primitive and better anti-inflammatory effects than other DSCs. In this respect, DFSCs have the potential to be of great clinical significance and translational value in oral and neurological diseases, with natural advantages based on their origin. Lastly, cryopreservation preserves the biological properties of DFSCs and enables them to be used as off-shelf products for clinical applications. This review summarizes and comments on the properties, application potential, and clinical transformation value of DFSCs, thereby inspiring novel perspectives in the future treatment of oral and neurological diseases.
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Affiliation(s)
- Chao Yang
- Research and Development Department, Shenzhen Uni-medica Technology Co., Ltd, Shenzhen 518051, Guangdong Province, China
- Department of Stomatology, The People’s Hospital of Longhua, Shenzhen 518109, Guangdong Province, China
| | - Xin-Ya Du
- Department of Stomatology, The People’s Hospital of Longhua, Shenzhen 518109, Guangdong Province, China
| | - Wen Luo
- Department of Stomatology, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China
- School of Stomatology, Hainan Medical University, Haikou 571199, Hainan Province, China
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Basabrain MS, Zhong J, Luo H, Liu J, Yi B, Zaeneldin A, Koh J, Zou T, Zhang C. Formation of Three-Dimensional Spheres Enhances the Neurogenic Potential of Stem Cells from Apical Papilla. Bioengineering (Basel) 2022; 9:604. [PMID: 36354515 PMCID: PMC9687952 DOI: 10.3390/bioengineering9110604] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/18/2022] [Accepted: 10/21/2022] [Indexed: 10/24/2023] Open
Abstract
UNLABELLED Cell-based neural regeneration is challenging due to the difficulty in obtaining sufficient neural stem cells with clinical applicability. Stem cells from apical papilla (SCAPs) originating from embryonic neural crests with high neurogenic potential could be a promising cell source for neural regeneration. This study aimed to investigate whether the formation of 3D spheres can promote SCAPs' neurogenic potential. MATERIAL AND METHODS Three-dimensional SCAP spheres were first generated in a 256-well agarose microtissue mold. The spheres and single cells were individually cultured on collagen I-coated μ-slides. Cell morphological changes, neural marker expression, and neurite outgrowth were evaluated by confocal microscope, ELISA, and RT-qPCR. RESULTS Pronounced morphological changes were noticed in a time-dependent manner. The migrating cells' morphology changed from fibroblast-like cells to neuron-like cells. Compared to the 2D culture, neurite length, number, and the expression of multiple progenitors, immature and mature neural markers were significantly higher in the 3D spheres. BDNF and NGF-β may play a significant role in the neural differentiation of SCAP spheres. CONCLUSION The formation of 3D spheres enhanced the neurogenic potential of SCAPs, suggesting the advantage of using the 3D spheres of SCAPs for treating neural diseases.
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Affiliation(s)
- Mohammed S. Basabrain
- Restorative Dental Sciences, Endodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
| | - Jialin Zhong
- Restorative Dental Sciences, Endodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
| | - Haiyun Luo
- Restorative Dental Sciences, Endodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
- Stomatological Hospital, Southern Medical University, 366 Jiangnan Avenue South, Guangzhou 510280, China
| | - Junqing Liu
- Restorative Dental Sciences, Endodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
| | - Baicheng Yi
- Restorative Dental Sciences, Endodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
| | - Ahmed Zaeneldin
- Restorative Dental Sciences, Cariology, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
| | - Junhao Koh
- Restorative Dental Sciences, Endodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
| | - Ting Zou
- Restorative Dental Sciences, Endodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
| | - Chengfei Zhang
- Restorative Dental Sciences, Endodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
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Morsczeck C. Mechanisms during Osteogenic Differentiation in Human Dental Follicle Cells. Int J Mol Sci 2022; 23:ijms23115945. [PMID: 35682637 PMCID: PMC9180518 DOI: 10.3390/ijms23115945] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 05/19/2022] [Accepted: 05/23/2022] [Indexed: 12/22/2022] Open
Abstract
Human dental follicle cells (DFCs) as periodontal progenitor cells are used for studies and research in regenerative medicine and not only in dentistry. Even if innovative regenerative therapies in medicine are often considered the main research area for dental stem cells, these cells are also very useful in basic research and here, for example, for the elucidation of molecular processes in the differentiation into mineralizing cells. This article summarizes the molecular mechanisms driving osteogenic differentiation of DFCs. The positive feedback loop of bone morphogenetic protein (BMP) 2 and homeobox protein DLX3 and a signaling pathway associated with protein kinase B (AKT) and protein kinase C (PKC) are presented and further insights related to other signaling pathways such as the WNT signaling pathway are explained. Subsequently, some works are presented that have investigated epigenetic modifications and non-coding ncRNAs and their connection with the osteogenic differentiation of DFCs. In addition, studies are presented that have shown the influence of extracellular matrix molecules or fundamental biological processes such as cellular senescence on osteogenic differentiation. The putative role of factors associated with inflammatory processes, such as interleukin 8, in osteogenic differentiation is also briefly discussed. This article summarizes the most important insights into the mechanisms of osteogenic differentiation in DFCs and is intended to be a small help in the direction of new research projects in this area.
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Affiliation(s)
- Christian Morsczeck
- Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
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Function of Dental Follicle Progenitor/Stem Cells and Their Potential in Regenerative Medicine: From Mechanisms to Applications. Biomolecules 2021; 11:biom11070997. [PMID: 34356621 PMCID: PMC8301812 DOI: 10.3390/biom11070997] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/04/2021] [Accepted: 07/04/2021] [Indexed: 02/06/2023] Open
Abstract
Dental follicle progenitor/stem cells (DFPCs) are a group of dental mesenchyme stem cells that lie in the dental follicle and play a critical role in tooth development and maintaining function. Originating from neural crest, DFPCs harbor a multipotential differentiation capacity. More importantly, they have superiorities, including the easy accessibility and abundant sources, active self-renewal ability and noncontroversial sources compared with other stem cells, making them an attractive candidate in the field of tissue engineering. Recent advances highlight the excellent properties of DFPCs in regeneration of orofacial tissues, including alveolar bone repair, periodontium regeneration and bio-root complex formation. Furthermore, they play a unique role in maintaining a favorable microenvironment for stem cells, immunomodulation and nervous related tissue regeneration. This review is intended to summarize the current knowledge of DFPCs, including their stem cell properties, physiological functions and clinical application potential. A deep understanding of DFPCs can thus inspire novel perspectives in regenerative medicine in the future.
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Yin JY, Luo XH, Feng WQ, Miao SH, Ning TT, Lei Q, Jiang T, Ma DD. Multidifferentiation potential of dental-derived stem cells. World J Stem Cells 2021; 13:342-365. [PMID: 34136070 PMCID: PMC8176842 DOI: 10.4252/wjsc.v13.i5.342] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 03/10/2021] [Accepted: 04/05/2021] [Indexed: 02/06/2023] Open
Abstract
Tooth-related diseases and tooth loss are widespread and are a major public health issue. The loss of teeth can affect chewing, speech, appearance and even psychology. Therefore, the science of tooth regeneration has emerged, and attention has focused on tooth regeneration based on the principles of tooth development and stem cells combined with tissue engineering technology. As undifferentiated stem cells in normal tooth tissues, dental mesenchymal stem cells (DMSCs), which are a desirable source of autologous stem cells, play a significant role in tooth regeneration. Researchers hope to reconstruct the complete tooth tissues with normal functions and vascularization by utilizing the odontogenic differentiation potential of DMSCs. Moreover, DMSCs also have the ability to differentiate towards cells of other tissue types due to their multipotency. This review focuses on the multipotential capacity of DMSCs to differentiate into various tissues, such as bone, cartilage, tendon, vessels, neural tissues, muscle-like tissues, hepatic-like tissues, eye tissues and glands and the influence of various regulatory factors, such as non-coding RNAs, signaling pathways, inflammation, aging and exosomes, on the odontogenic/osteogenic differentiation of DMSCs in tooth regeneration. The application of DMSCs in regenerative medicine and tissue engineering will be improved if the differentiation characteristics of DMSCs can be fully utilized, and the factors that regulate their differentiation can be well controlled.
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Affiliation(s)
- Jing-Yao Yin
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Xing-Hong Luo
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Wei-Qing Feng
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Sheng-Hong Miao
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Ting-Ting Ning
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
| | - Qian Lei
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Tao Jiang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Dan-Dan Ma
- Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China
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8
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Angiogenesis in Regenerative Dentistry: Are We Far Enough for Therapy? Int J Mol Sci 2021; 22:ijms22020929. [PMID: 33477745 PMCID: PMC7832295 DOI: 10.3390/ijms22020929] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 01/14/2021] [Accepted: 01/15/2021] [Indexed: 12/14/2022] Open
Abstract
Angiogenesis is a broad spread term of high interest in regenerative medicine and tissue engineering including the dental field. In the last two decades, researchers worldwide struggled to find the best ways to accelerate healing, stimulate soft, and hard tissue remodeling. Stem cells, growth factors, pathways, signals, receptors, genetics are just a few words that describe this area in medicine. Dental implants, bone and soft tissue regeneration using autologous grafts, or xenografts, allografts, their integration and acceptance rely on their material properties. However, the host response, through its vascularization, plays a significant role. The present paper aims to analyze and organize the latest information about the available dental stem cells, the types of growth factors with pro-angiogenic effect and the possible therapeutic effect of enhanced angiogenesis in regenerative dentistry.
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9
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Ryu JS, Jeong EJ, Kim JY, Park SJ, Ju WS, Kim CH, Kim JS, Choo YK. Application of Mesenchymal Stem Cells in Inflammatory and Fibrotic Diseases. Int J Mol Sci 2020; 21:ijms21218366. [PMID: 33171878 PMCID: PMC7664655 DOI: 10.3390/ijms21218366] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 10/29/2020] [Accepted: 11/05/2020] [Indexed: 02/07/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from various tissues in the adult body. MSCs should be characterized by three criteria for regenerative medicine. MSCs must (1) adhere to plastic surfaces, (2) express specific surface antigens, and (3) differentiate into mesodermal lineages, including chondrocytes, osteoblasts, and adipocytes, in vitro. Interestingly, MSCs have immunomodulatory features and secrete trophic factors and immune receptors that regulate the microenvironment in host tissue. These specific and unique therapeutic properties make MSCs ideal as therapeutic agents in vivo. Specifically, pre-clinical and clinical investigators generated inflammatory and fibrotic diseases models, and then transplantation of MSCs into diseases models for therapeutic effects investigation. In this review, we characterize MSCs from various tissues and describe their applications for treating various inflammation and fibrotic diseases.
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Affiliation(s)
- Jae-Sung Ryu
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University, Daejeon 35365, Korea; (J.-S.R.); (J.-Y.K.)
- Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon 35365, Korea
| | - Eun-Jeong Jeong
- Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 54538, Korea; (E.-J.J.); (S.J.P.); (W.S.J.)
- Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea;
| | - Jong-Yeup Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Konyang University, Daejeon 35365, Korea; (J.-S.R.); (J.-Y.K.)
- Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon 35365, Korea
| | - Soon Ju Park
- Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 54538, Korea; (E.-J.J.); (S.J.P.); (W.S.J.)
- Institute for Glycoscience, Wonkwang University, Iksan 54538, Korea
| | - Won Seok Ju
- Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 54538, Korea; (E.-J.J.); (S.J.P.); (W.S.J.)
- Institute for Glycoscience, Wonkwang University, Iksan 54538, Korea
| | - Chang-Hyun Kim
- College of Medicine, Dongguk University, Goyang 10326, Korea;
| | - Jang-Seong Kim
- Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea;
- Department of Functional Genomics, University of Science and Technology (UST), Daejeon 34141, Korea
| | - Young-Kug Choo
- Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 54538, Korea; (E.-J.J.); (S.J.P.); (W.S.J.)
- Institute for Glycoscience, Wonkwang University, Iksan 54538, Korea
- Correspondence:
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10
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Biomimetic Aspects of Oral and Dentofacial Regeneration. Biomimetics (Basel) 2020; 5:biomimetics5040051. [PMID: 33053903 PMCID: PMC7709662 DOI: 10.3390/biomimetics5040051] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/09/2020] [Accepted: 10/10/2020] [Indexed: 12/12/2022] Open
Abstract
Biomimetic materials for hard and soft tissues have advanced in the fields of tissue engineering and regenerative medicine in dentistry. To examine these recent advances, we searched Medline (OVID) with the key terms “biomimetics”, “biomaterials”, and “biomimicry” combined with MeSH terms for “dentistry” and limited the date of publication between 2010–2020. Over 500 articles were obtained under clinical trials, randomized clinical trials, metanalysis, and systematic reviews developed in the past 10 years in three major areas of dentistry: restorative, orofacial surgery, and periodontics. Clinical studies and systematic reviews along with hand-searched preclinical studies as potential therapies have been included. They support the proof-of-concept that novel treatments are in the pipeline towards ground-breaking clinical therapies for orofacial bone regeneration, tooth regeneration, repair of the oral mucosa, periodontal tissue engineering, and dental implants. Biomimicry enhances the clinical outcomes and calls for an interdisciplinary approach integrating medicine, bioengineering, biotechnology, and computational sciences to advance the current research to clinics. We conclude that dentistry has come a long way apropos of regenerative medicine; still, there are vast avenues to endeavour, seeking inspiration from other facets in biomedical research.
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11
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Morsczeck C. Effects of Cellular Senescence on Dental Follicle Cells. Pharmacology 2020; 106:137-142. [PMID: 32980839 DOI: 10.1159/000510014] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 07/08/2020] [Indexed: 12/11/2022]
Abstract
The dental follicle is part of the tooth germ, and isolated stem cells from this tissue (dental follicle cells; DFCs) are considered, for example, for regenerative medicine and immunotherapies. However somatic stem cells can also improve pharmaceutical research. Cell proliferation is limited by the induction of senescence, which, while reducing the therapeutic potential of DFCs for cell therapy, can also be used to study aging processes at the cellular level that can be used to test anti-aging pharmaceuticals. Unfortunately, very little is known about cellular senescence in DFCs. This review presents current knowledge about cellular senescence in DFCs.
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Affiliation(s)
- Christian Morsczeck
- Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany,
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12
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Zafar MS, Amin F, Fareed MA, Ghabbani H, Riaz S, Khurshid Z, Kumar N. Biomimetic Aspects of Restorative Dentistry Biomaterials. Biomimetics (Basel) 2020; 5:E34. [PMID: 32679703 PMCID: PMC7557867 DOI: 10.3390/biomimetics5030034] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 07/08/2020] [Accepted: 07/10/2020] [Indexed: 12/15/2022] Open
Abstract
Biomimetic has emerged as a multi-disciplinary science in several biomedical subjects in recent decades, including biomaterials and dentistry. In restorative dentistry, biomimetic approaches have been applied for a range of applications, such as restoring tooth defects using bioinspired peptides to achieve remineralization, bioactive and biomimetic biomaterials, and tissue engineering for regeneration. Advancements in the modern adhesive restorative materials, understanding of biomaterial-tissue interaction at the nano and microscale further enhanced the restorative materials' properties (such as color, morphology, and strength) to mimic natural teeth. In addition, the tissue-engineering approaches resulted in regeneration of lost or damaged dental tissues mimicking their natural counterpart. The aim of the present article is to review various biomimetic approaches used to replace lost or damaged dental tissues using restorative biomaterials and tissue-engineering techniques. In addition, tooth structure, and various biomimetic properties of dental restorative materials and tissue-engineering scaffold materials, are discussed.
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Affiliation(s)
- Muhammad Sohail Zafar
- Department of Restorative Dentistry, College of Dentistry, Taibah University, Al Madinah, Al Munawwarah 41311, Saudi Arabia;
- Department of Dental Materials, Islamic International Dental College, Riphah International University, Islamabad 44000, Pakistan
| | - Faiza Amin
- Science of Dental Materials Department, Dow Dental College, Dow University of Health Sciences, Karachi 74200, Pakistan;
| | - Muhmmad Amber Fareed
- Adult Restorative Dentistry, Dental Biomaterials and Prosthodontics Oman Dental College, Muscat 116, Sultanate of Oman;
| | - Hani Ghabbani
- Department of Restorative Dentistry, College of Dentistry, Taibah University, Al Madinah, Al Munawwarah 41311, Saudi Arabia;
| | - Samiya Riaz
- School of Dental Sciences, Universiti Sains Malaysia Health Campus, Kubang Kerian 16150, Kelantan, Malaysia;
| | - Zohaib Khurshid
- Department of Prosthodontics and Dental Implantology, College of Dentistry, King Faisal University, Al-Ahsa 31982, Saudia Arabia;
| | - Naresh Kumar
- Department of Science of Dental Materials, Dow University of Health Sciences, Karachi 74200, Pakistan;
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13
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Ito K, Tomoki R, Ogura N, Takahashi K, Eda T, Yamazaki F, Kato Y, Goss A, Kondoh T. MicroRNA-204 regulates osteogenic induction in dental follicle cells. J Dent Sci 2020; 15:457-465. [PMID: 33505617 PMCID: PMC7816036 DOI: 10.1016/j.jds.2019.11.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 10/08/2019] [Indexed: 11/16/2022] Open
Abstract
The dental follicle is an ectomesenchymal tissue surrounding developing tooth germ that contains osteoblastic-lineage-committed stem/progenitor cells. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression during stem cell growth, proliferation, and differentiation. The aim of this study was to investigate the key regulators of miRNA during osteogenic differentiation in human dental follicle cells (hDFC). We analyzed miRNA expression profiles in hDFC during osteoblastic differentiation. Expression of miR-204 was decreased in hDFC during osteogenic induction on microarray analysis. Real-time and RT-PCR analysis also showed that the expression of miR-204 was decreased in all three hDFC during osteogenic differentiation. To investigate whether miR-204 has an effect on osteogenic differentiation, miR-204 was predicted to target alkaline phosphatase (ALP), secreted protein acidic and rich in cysteine (SPARC), and Runx2 in the in the 3'-UTRs by in silico analysis. When miR-204 was transfected into hDFC, the activity of ALP and protein levels of SPARC and Runx2 were decreased. mRNA levels of ALP, SPARC and Runx2 were also decreased by miR-204 transfection. Our data suggest that miR-204 negatively regulates the osteogenic differentiation of hDFC by targeting the bone-specific transcription factor Runx2, the mineralization maker ALP and the bone extracellular matrix protein SPARC.
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Affiliation(s)
- Ko Ito
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Chiba, Japan.,Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Chiba, Japan
| | - Risa Tomoki
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Chiba, Japan
| | - Naomi Ogura
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Chiba, Japan.,Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Chiba, Japan
| | - Kosuke Takahashi
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Chiba, Japan.,Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Chiba, Japan
| | - Takashi Eda
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Chiba, Japan
| | - Fumie Yamazaki
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Chiba, Japan
| | - Yugo Kato
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Chiba, Japan
| | - Alastair Goss
- Oral and Maxillofacial Surgery Unit, Faculty of Health Science, University of Adelaide, South Australia, Australia
| | - Toshirou Kondoh
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Chiba, Japan.,Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Chiba, Japan
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14
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Dental Follicle Cells: Roles in Development and Beyond. Stem Cells Int 2019; 2019:9159605. [PMID: 31636679 PMCID: PMC6766151 DOI: 10.1155/2019/9159605] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Accepted: 08/16/2019] [Indexed: 02/05/2023] Open
Abstract
Dental follicle cells (DFCs) are a group of mesenchymal progenitor cells surrounding the tooth germ, responsible for cementum, periodontal ligament, and alveolar bone formation in tooth development. Cascades of signaling pathways and transcriptional factors in DFCs are involved in directing tooth eruption and tooth root morphogenesis. Substantial researches have been made to decipher multiple aspects of DFCs, including multilineage differentiation, senescence, and immunomodulatory ability. DFCs were proved to be multipotent progenitors with decent amplification, immunosuppressed and acquisition ability. They are able to differentiate into osteoblasts/cementoblasts, adipocytes, neuron-like cells, and so forth. The excellent properties of DFCs facilitated clinical application, as exemplified by bone tissue engineering, tooth root regeneration, and periodontium regeneration. Except for the oral and maxillofacial regeneration, DFCs were also expected to be applied in other tissues such as spinal cord defects (SCD), cardiomyocyte destruction. This article reviewed roles of DFCs in tooth development, their properties, and clinical application potentials, thus providing a novel guidance for tissue engineering.
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15
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Koch F, Ekat K, Kilian D, Hettich T, Germershaus O, Lang H, Peters K, Kreikemeyer B. A Versatile Biocompatible Antibiotic Delivery System Based on Self-Assembling Peptides with Antimicrobial and Regenerative Potential. Adv Healthc Mater 2019; 8:e1900167. [PMID: 30985084 DOI: 10.1002/adhm.201900167] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 03/20/2019] [Indexed: 12/16/2022]
Abstract
Periodontitis is a chronic inflammatory and tissue-destructive disease. Since the polymicrobiome in the oral cavity makes it difficult to treat, novel therapeutic strategies are required. Hydrogels based on self-assembling peptides (SAP) can be suitable candidates for periodontal therapy due to their injectability, biocompatibility, cargo-loading capacity, and tunable physicochemical and mechanical properties. In this study, two SAP hydrogels (P11-4 and P11-28/29) are examined for their intrinsic antimicrobial activity, regenerative potential, and antibiotic delivery capacity. A significant antibacterial effect of P11-28/29 hydrogels on the periodontal pathogen Porphyromonas gingivalis and a less pronounced effect for P11-4 hydrogels is demonstrated. The metabolic activity rates of human dental follicle stem cells (DFSCs), which reflect cell viability and may thus indicate the regenerative capacity, are similar on tissue culture polystyrene (TCPS) and on P11-4 hydrogels after 14 days of culture. Noticeably, both SAP hydrogels strengthen the osteogenic differentiation of DFSCs compared with TCPS. The incorporation of tetracycline, ciprofloxacin, and doxycycline does not affect fibril formation of either SAP hydrogel and results in favorable release kinetics up to 120 h. In summary, this study reveals that P11-SAP hydrogels combine many favorable properties required to make them applicable as prospective novel treatment strategy for periodontal therapy.
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Affiliation(s)
- Franziska Koch
- School of Life SciencesInstitute for Chemistry and BioanalyticsUniversity of Applied Sciences and Arts Northwestern Switzerland 4132 Muttenz Switzerland
- Institute of Medical MicrobiologyVirology and HygieneUniversity Medicine Rostock 18057 Rostock Germany
- Department of Cell BiologyUniversity Medicine Rostock 18057 Rostock Germany
| | - Katharina Ekat
- Institute of Medical MicrobiologyVirology and HygieneUniversity Medicine Rostock 18057 Rostock Germany
- Department of Cell BiologyUniversity Medicine Rostock 18057 Rostock Germany
- Clinic for Restorative Dentistry and PeriodontologyUniversity Medicine Rostock 18057 Rostock Germany
| | - David Kilian
- School of Life SciencesInstitute for Chemistry and BioanalyticsUniversity of Applied Sciences and Arts Northwestern Switzerland 4132 Muttenz Switzerland
| | - Timm Hettich
- School of Life SciencesInstitute for Chemistry and BioanalyticsUniversity of Applied Sciences and Arts Northwestern Switzerland 4132 Muttenz Switzerland
| | - Oliver Germershaus
- School of Life SciencesInstitute of Pharma TechnologyUniversity of Applied Sciences and Arts Northwestern Switzerland 4132 Muttenz Switzerland
| | - Herrmann Lang
- Clinic for Restorative Dentistry and PeriodontologyUniversity Medicine Rostock 18057 Rostock Germany
| | - Kirsten Peters
- Department of Cell BiologyUniversity Medicine Rostock 18057 Rostock Germany
| | - Bernd Kreikemeyer
- Institute of Medical MicrobiologyVirology and HygieneUniversity Medicine Rostock 18057 Rostock Germany
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16
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Wang D, Wang Y, Tian W, Pan J. Advances of tooth-derived stem cells in neural diseases treatments and nerve tissue regeneration. Cell Prolif 2019; 52:e12572. [PMID: 30714230 PMCID: PMC6536383 DOI: 10.1111/cpr.12572] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 12/05/2018] [Accepted: 12/06/2018] [Indexed: 02/05/2023] Open
Abstract
Nerous system diseases, both central and peripheral, bring an incredible burden onto patients and enormously reduce their quality of life. Currently, there are still no effective treatments to repair nerve lesions that do not have side effects. Stem cell-based therapies, especially those using dental stem cells, bring new hope to neural diseases. Dental stem cells, derived from the neural crest, have many characteristics that are similar to neural cells, indicating that they can be an ideal source of cells for neural regeneration and repair. This review summarizes the neural traits of all the dental cell types, including DPSCs, PDLCs, DFCs, APSCs and their potential applications in nervous system diseases. We have summed up the advantages of dental stem cells in neural repair, such as their neurotrophic and neuroprotective traits, easy harvest and low rejective reaction rate, among others. Taken together, dental stem cells are an ideal cell source for neural tissue regeneration and repair.
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Affiliation(s)
- Dianri Wang
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Yuhao Wang
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Weidong Tian
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Jian Pan
- State Key Laboratory of Oral Disease, West China Hospital of StomatologySichuan UniversityChengduChina
- Department of Oral and Maxillofacial Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
- National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduChina
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17
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Bone Tissue Engineering Using Human Cells: A Comprehensive Review on Recent Trends, Current Prospects, and Recommendations. APPLIED SCIENCES-BASEL 2019. [DOI: 10.3390/app9010174] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The use of proper cells for bone tissue engineering remains a major challenge worldwide. Cells play a pivotal role in the repair and regeneration of the bone tissue in vitro and in vivo. Currently, a large number of differentiated (somatic) and undifferentiated (stem) cells have been used for bone reconstruction alone or in combination with different biomaterials and constructs (e.g., scaffolds). Although the results of the cell transplantation without any supporting or adjuvant material have been very effective with regard to bone healing. Recent advances in bone scaffolding are now becoming new players affecting the osteogenic potential of cells. In the present study, we have critically reviewed all the currently used cell sources for bone reconstruction and discussed the new horizons that are opening up in the context of cell-based bone tissue engineering strategies.
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18
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Martellucci S, Manganelli V, Santacroce C, Santilli F, Piccoli L, Sorice M, Mattei V. Role of Prion protein-EGFR multimolecular complex during neuronal differentiation of human dental pulp-derived stem cells. Prion 2018; 12:117-126. [PMID: 29644924 DOI: 10.1080/19336896.2018.1463797] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Cellular prion protein (PrPC) is expressed in a wide variety of stem cells in which regulates their self-renewal as well as differentiation potential. In this study we investigated the presence of PrPC in human dental pulp-derived stem cells (hDPSCs) and its role in neuronal differentiation process. We show that hDPSCs expresses early PrPC at low concentration and its expression increases after two weeks of treatment with EGF/bFGF. Then, we analyzed the association of PrPC with gangliosides and EGF receptor (EGF-R) during neuronal differentiation process. PrPC associates constitutively with GM2 in control hDPSCs and with GD3 only after neuronal differentiation. Otherwise, EGF-R associates weakly in control hDPSCs and more markedly after neuronal differentiation. To analyze the functional role of PrPC in the signal pathway mediated by EGF/EGF-R, a siRNA PrP was applied to ablate PrPC and its function. The treatment with siRNA PrP significantly prevented Akt and ERK1/2 phosphorylation induced by EGF. Moreover, siRNA PrP treatment significantly prevented neuronal-specific antigens expression induced by EGF/bFGF, indicating that cellular prion protein is essential for EGF/bFGF-induced hDPSCs differentiation. These results suggest that PrPC interact with EGF-R within lipid rafts, playing a role in the multimolecular signaling complexes involved in hDPSCs neuronal differentiation.
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Affiliation(s)
- Stefano Martellucci
- a Laboratory of Experimental Medicine and Environmental Pathology - Rieti University Hub "Sabina Universitas" , Via Angelo Maria Ricci 35/A, Rieti , Italy.,b Department of Experimental Medicine - "Sapienza" University , Viale Regina Elena 324, Rome , Italy
| | - Valeria Manganelli
- b Department of Experimental Medicine - "Sapienza" University , Viale Regina Elena 324, Rome , Italy
| | - Costantino Santacroce
- a Laboratory of Experimental Medicine and Environmental Pathology - Rieti University Hub "Sabina Universitas" , Via Angelo Maria Ricci 35/A, Rieti , Italy
| | - Francesca Santilli
- a Laboratory of Experimental Medicine and Environmental Pathology - Rieti University Hub "Sabina Universitas" , Via Angelo Maria Ricci 35/A, Rieti , Italy
| | - Luca Piccoli
- c Department of Science Dentistry and Maxillofacial - "Sapienza" University , Viale Regina Elena 287/A, Rome , Italy
| | - Maurizio Sorice
- b Department of Experimental Medicine - "Sapienza" University , Viale Regina Elena 324, Rome , Italy
| | - Vincenzo Mattei
- a Laboratory of Experimental Medicine and Environmental Pathology - Rieti University Hub "Sabina Universitas" , Via Angelo Maria Ricci 35/A, Rieti , Italy.,b Department of Experimental Medicine - "Sapienza" University , Viale Regina Elena 324, Rome , Italy
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19
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Heng BC, Gong T, Wang S, Lim LW, Wu W, Zhang C. Decellularized Matrix Derived from Neural Differentiation of Embryonic Stem Cells Enhances the Neurogenic Potential of Dental Follicle Stem Cells. J Endod 2018; 43:409-416. [PMID: 28231979 DOI: 10.1016/j.joen.2016.10.033] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Revised: 10/07/2016] [Accepted: 10/22/2016] [Indexed: 11/18/2022]
Abstract
INTRODUCTION Dental follicle stem cells (DFSCs) possess neurogenic potential because they originate from the embryonic neural crest. This study investigated whether neural differentiation of DFSCs can be enhanced by culture on decellularized matrix substrata (NSC-DECM) derived from neurogenesis of human embryonic stem cells (hESCs). METHODS The hESCs were differentiated into neural stem cells (NSCs), and NSC-DECM was extracted from confluent monolayers of NSCs through treatment with deionized water. DFSCs seeded on NSC-DECM, Geltrex, and tissue culture polystyrene (TCPS) were subjected to neural induction during a period of 21 days. Expression of early/intermediate (Musashi1, PAX6, NSE, and βIII-tubulin) and mature/late (NGN2, NeuN, NFM, and MASH1) neural markers by DFSCs was analyzed at the 7-, 14-, and 21-day time points with quantitative real-time polymerase chain reaction. Immunocytochemistry for detection of βIII-tubulin, PAX6, and NGN2 expression by DFSCs on day 7 of neural induction was also carried out. RESULTS Quantitative RT-PCR showed that expression of PAX6, Musashi1, βIII-tubulin, NSE, NGN2, and NFM by DFSCs was enhanced on NSC-DECM versus either the Geltrex or TCPS groups. Immunocytochemistry showed that DFSCs in the NSC-DECM group displayed more intense staining for βIII-tubulin, PAX6, and NGN2 expression, together with more neurite outgrowths and elongated morphology, as compared with either Geltrex or TCPS. CONCLUSIONS DECM derived from neurogenesis of hESCs can enhance the neurogenic potential of DFSCs.
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Affiliation(s)
- Boon Chin Heng
- Endodontology, Faculty of Dentistry, University of Hong Kong, Pokfulam, Hong Kong, China; Department of Biological Sciences, Sunway University, Bandar Sunway, Selangor Darul Ehsan, Malaysia
| | - Ting Gong
- Endodontology, Faculty of Dentistry, University of Hong Kong, Pokfulam, Hong Kong, China
| | - Shuai Wang
- ENT Institute of Shenzhen, Shenzhen Longgang ENT Hospital, Shenzhen, China
| | - Lee Wei Lim
- Department of Biological Sciences, Sunway University, Bandar Sunway, Selangor Darul Ehsan, Malaysia; School of Biomedical Sciences, University of Hong Kong, Pokfulam, Hong Kong, China
| | - Wutian Wu
- School of Biomedical Sciences, University of Hong Kong, Pokfulam, Hong Kong, China
| | - Chengfei Zhang
- Endodontology, Faculty of Dentistry, University of Hong Kong, Pokfulam, Hong Kong, China; HKU Shenzhen Institute of Research and Innovation, Hong Kong, China.
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20
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Morsczeck C, Reichert TE. Dental stem cells in tooth regeneration and repair in the future. Expert Opin Biol Ther 2017; 18:187-196. [PMID: 29110535 DOI: 10.1080/14712598.2018.1402004] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Human dental stem cells can be obtained from postnatal teeth, extracted wisdom teeth or exfoliated deciduous teeth. Due to their differentiation potential, these mesenchymal stem cells are promising for tooth repair. Therefore, the development of dental tissue regeneration represents a suitable but challenging, target for dental stem cell therapies. Areas covered: Expert opinion: AREAS COVERED In this review, the authors provide an overview of human dental stem cells and their properties for regeneration medicine. Numerous preclinical studies have shown that dental stem cells improve bone augmentation and healing of periodontal diseases. Clinical trials are ongoing to validate the clinical feasibility of these approaches. Dental stem cells are also important for basic research. EXPERT OPINION Dental stem cells offer numerous advantages for tooth repair and regeneration. Data obtained from different studies are encouraging. In the next few years, investigations on dental stem cells in basic research, pre-clinical research and clinical studies will pave the way to optimizing patient-tailored treatments for repair and regeneration of dental tissues.
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Affiliation(s)
- Christian Morsczeck
- a Department of Cranio-Maxillofacial Surgery , Hospital of the University of Regensburg , Regensburg , Germany
| | - Torsten E Reichert
- a Department of Cranio-Maxillofacial Surgery , Hospital of the University of Regensburg , Regensburg , Germany
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21
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Nie L, Yang X, Duan L, Huang E, Pengfei Z, Luo W, Zhang Y, Zeng X, Qiu Y, Cai T, Li C. The healing of alveolar bone defects with novel bio-implants composed of Ad-BMP9-transfected rDFCs and CHA scaffolds. Sci Rep 2017; 7:6373. [PMID: 28743897 PMCID: PMC5527078 DOI: 10.1038/s41598-017-06548-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 06/15/2017] [Indexed: 12/17/2022] Open
Abstract
Cells, scaffolds, and growth factors play important roles in bone regeneration. Bone morphogenetic protein 9 (BMP9), a member of BMP family, could facilitate osteogenesis by regulating growth factors and promoting angiogenesis. Similar to other stem cells, rat dental follicle stem cells (rDFCs), the precursor cells of cementoblasts, osteoblasts and periodontal ligament cells, can self-renew and exhibit multipotential capacity. Coralline hydroxyapatite (CHA) has good biocompatibility and conductivity required for bone tissue engineering. Here, we reported that BMP9 could enhance the osteogenic differentiation of rDFCs in cell culture. Moreover, our results suggested that BMP9 acted through the Smad1/5/8 signaling pathway. We also produced a novel scaffold that encompasses bio-degradable CHA seeded with recombinant adenoviruses expressing BMP9-transfected rDFCs (Ad-BMP9-transfected rDFCs). With this implant, we achieved more alveolar bone regeneration in the alveolar bone defect compared to blank group, CHA group and rDFCs group. Our results provided a novel bio-implants composed of Ad-BMP9-transfected rDFCs and CHA scaffolds and its mechanism is regarding the activation of Smad1/5/8 signaling pathway in BMP9-induced rDFCs osteogenesis.
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Affiliation(s)
- Li Nie
- Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key, Chongqing, 401147, China
- Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Xia Yang
- Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key, Chongqing, 401147, China
- Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Liang Duan
- Department of Laboratory Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Enyi Huang
- Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key, Chongqing, 401147, China
- Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Zhou Pengfei
- Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key, Chongqing, 401147, China
- Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Wenping Luo
- Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key, Chongqing, 401147, China
- Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Yan Zhang
- Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key, Chongqing, 401147, China
- Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Xingqi Zeng
- Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key, Chongqing, 401147, China
- Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Ye Qiu
- Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key, Chongqing, 401147, China
- Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Ting Cai
- Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key, Chongqing, 401147, China
- Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Conghua Li
- Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China.
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key, Chongqing, 401147, China.
- Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China.
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22
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Capacity of Human Dental Follicle Cells to Differentiate into Neural Cells In Vitro. Stem Cells Int 2017; 2017:8371326. [PMID: 28261273 PMCID: PMC5316458 DOI: 10.1155/2017/8371326] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Accepted: 12/28/2016] [Indexed: 01/12/2023] Open
Abstract
The dental follicle is an ectomesenchymal tissue surrounding the developing tooth germ. Human dental follicle cells (hDFCs) have the capacity to commit to differentiation into multiple cell types. Here we investigated the capacity of hDFCs to differentiate into neural cells and the efficiency of a two-step strategy involving floating neurosphere-like bodies for neural differentiation. Undifferentiated hDFCs showed a spindle-like morphology and were positive for neural markers such as nestin, β-III-tubulin, and S100β. The cellular morphology of several cells was neuronal-like including branched dendrite-like processes and neurites. Next, hDFCs were used for neurosphere formation in serum-free medium containing basic fibroblast growth factor, epidermal growth factor, and B27 supplement. The number of cells with neuronal-like morphology and that were strongly positive for neural markers increased with sphere formation. Gene expression of neural markers also increased in hDFCs with sphere formation. Next, gene expression of neural markers was examined in hDFCs during neuronal differentiation after sphere formation. Expression of Musashi-1 and Musashi-2, MAP2, GFAP, MBP, and SOX10 was upregulated in hDFCs undergoing neuronal differentiation via neurospheres, whereas expression of nestin and β-III-tubulin was downregulated. In conclusion, hDFCs may be another optimal source of neural/glial cells for cell-based therapies to treat neurological diseases.
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23
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Human dental follicle cells express embryonic, mesenchymal and neural stem cells markers. Arch Oral Biol 2017; 73:121-128. [DOI: 10.1016/j.archoralbio.2016.10.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2015] [Revised: 09/21/2016] [Accepted: 10/06/2016] [Indexed: 12/13/2022]
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Okada H, Takahashi K, Ogura N, Tomoki R, Ito K, Kondoh T. Plasma rich in growth factors stimulates proliferation, migration, and gene expression associated with bone formation in human dental follicle cells. J Dent Sci 2016; 11:245-252. [PMID: 30894980 PMCID: PMC6395260 DOI: 10.1016/j.jds.2015.12.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Revised: 12/01/2015] [Indexed: 02/04/2023] Open
Abstract
Background/purpose Plasma rich in growth factors (PRGFs), which is prepared from autologous blood from patients, has been reported with regards to bone regeneration for dental implants. Human dental follicle cells (hDFCs) have the capacity to commit to multiple cell types such as the osteoblastic lineage. The aim of this study is to evaluate the effects of PRGFs for mineralization in hDFCs. Materials and methods PRGFs was prepared from whole blood centrifuged at 460g for 8 minutes. hDFCs isolated from the dental follicle with collagenase/dispase were cultured with growth medium or osteogenic induction medium (OIM) containing PRGFs or fetal bovine serum. Concentrations of the growth factors were examined using an enzyme-linked immunosorbent assay kit. A cell migration assay was used for two-dimensional movement. Gene expressions were examined with real-time polymerase chain reaction using a DyNAmo SYBR Green quantitative polymerase chain reaction kit. Results The platelet concentration in PRGF Fraction 2 was 2.14-fold higher than in whole blood. White blood cells were not detected in PRGFs. Transforming growth factor-β levels were higher than insulin-like growth factor-1, platelet-derived growth factor-AB and -BB, and vascular endothelial growth factors in PRGF Fraction 2. Proliferation and migration by hDFCs increased in OIM supplemented with PRGFs in a dose-dependent manner and were higher in hDFCs cultured in OIM plus 10% PRGFs compared with OIM plus 10% fetal bovine serum. PRGFs upregulated the gene expression of type I collagen, osteomodulin, alkaline phosphatase, bone morphogenic protein-4, and transforming growth factor-β in hDFCs. Conclusion PRGFs may promote bone regeneration due to it including high levels of growth factors.
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Affiliation(s)
- Hitoe Okada
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Japan
| | - Kosuke Takahashi
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.,Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Matsudo, Japan
| | - Naomi Ogura
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.,Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Matsudo, Japan
| | - Risa Tomoki
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Japan
| | - Ko Ito
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.,Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Matsudo, Japan
| | - Toshirou Kondoh
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.,Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Matsudo, Japan
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Ullah I, Subbarao RB, Kim EJ, Bharti D, Jang SJ, Park JS, Shivakumar SB, Lee SL, Kang D, Byun JH, Park BW, Rho GJ. In vitro comparative analysis of human dental stem cells from a single donor and its neuronal differentiation potential evaluated by electrophysiology. Life Sci 2016; 154:39-51. [PMID: 27107840 DOI: 10.1016/j.lfs.2016.04.026] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Revised: 04/12/2016] [Accepted: 04/19/2016] [Indexed: 01/09/2023]
Abstract
AIMS The aim of this study was to find out a mesenchymal stem cells (MSCs) source from human dental tissues of the same donor (follicle, papilla and pulp), which exhibits higher neurogenic differentiation potential in vitro. MAIN METHODS MSCs were isolated from dental tissues (follicle, papilla and pulp) by digestion method. All MSCs were analyzed for pluripotent makers by western blot, cell surface markers by flow cytometry, adipo- and osteocytes markers by RT-qPCR. The neuronal differentiated MSCs were characterized for neuronal specific markers by RT-qPCR and immunofluorescence. Functional neuronal properties were analyzed by electrophysiology and synaptic markers expression. KEY FINDINGS All MSCs expressed pluripotent markers (Oct4, Sox2 and Nanog) and were found positive for mesenymal markers (CD44, CD90, CD105) while negative for hematopoietic markers (CD34 and CD45). Furthermore, MSCs were successfully differentiated into adipocytes, osteocytes and trans-differentiated into neuronal cells. Among them, dental pulp derived MSCs exhibits higher neurogenic differentiation potential, in term of expression of neuronal specific markers at both gene and protein level, and having higher Na(+) and K(+) current with the expression of synaptic markers. SIGNIFICANCE The three types of dental MSCs from a single donor broadly possessed similar cellular properties and can differentiate into neuronal cells; however, pulp derived MSCs showed higher neurogenic potential than the follicle and papilla, suggesting their use in future stem cells therapy for the treatment of neurodegenerative disorders.
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Affiliation(s)
- Imran Ullah
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Raghavendra Baregundi Subbarao
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Eun-Jin Kim
- Department of Physiology and Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751, Republic of Korea
| | - Dinesh Bharti
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Si-Jung Jang
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Ji-Sung Park
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Sharath Belame Shivakumar
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Sung-Lim Lee
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea
| | - Dawon Kang
- Department of Physiology and Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751, Republic of Korea
| | - June-Ho Byun
- Department of Oral and Maxillofacial Surgery, Institute of Health Science, School of Medicine, Gyeongsang National University, Republic of Korea
| | - Bong-Wook Park
- Department of Oral and Maxillofacial Surgery, Institute of Health Science, School of Medicine, Gyeongsang National University, Republic of Korea.
| | - Gyu-Jin Rho
- Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
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Heng BC, Lim LW, Wu W, Zhang C. An Overview of Protocols for the Neural Induction of Dental and Oral Stem Cells In Vitro. TISSUE ENGINEERING PART B-REVIEWS 2016; 22:220-50. [PMID: 26757369 DOI: 10.1089/ten.teb.2015.0488] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
To date, various adult stem cells have been identified within the oral cavity, including dental pulp stem cells, dental follicle stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, periodontal ligament stem cells, and mesenchymal stem cells from the gingiva. All of these possess neurogenic potential due to their common developmental origin from the embryonic neural crest. Besides the relative ease of isolation of these adult stem cells from readily available biological waste routinely produced during dental treatment, these cells also possess the advantage of immune compatibility in autologous transplantation. In recent years, much interest has been focused on the derivation of neural lineages from these adult stem cells for therapeutic applications in the brain, spinal cord, and peripheral nerve regeneration. In addition, there are also promising nontherapeutic applications of stem cell-derived neurons in pharmacological and toxicological screening of neuroactive drugs, and for in vitro modeling of neurodevelopmental and neurodegenerative diseases. Hence, this review will critically examine the diverse array of in vitro neural induction protocols that have been devised for dental and oral-derived stem cells. These protocols are defined not only by the culture milieu comprising the basal medium plus growth factors, small molecules, and other culture supplements but also by the substrata/surface coatings utilized, the presence of multiple culture stages, the total culture duration, the initial seeding density, and whether the spheroid/neurosphere formation is being utilized to recapitulate the three-dimensional neural differentiation microenvironment that is naturally present physiologically in vivo.
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Affiliation(s)
- Boon Chin Heng
- 1 Comprehensive Dental Care, Endodonthics, Faculty of Dentistry, The University of Hong Kong , Pokfulam, Hong Kong
| | - Lee Wei Lim
- 2 School of Biomedical Sciences, The University of Hong Kong , Pokfulam, Hong Kong
| | - Wutian Wu
- 2 School of Biomedical Sciences, The University of Hong Kong , Pokfulam, Hong Kong
| | - Chengfei Zhang
- 1 Comprehensive Dental Care, Endodonthics, Faculty of Dentistry, The University of Hong Kong , Pokfulam, Hong Kong
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Tian Y, Bai D, Guo W, Li J, Zeng J, Yang L, Jiang Z, Feng L, Yu M, Tian W. Comparison of human dental follicle cells and human periodontal ligament cells for dentin tissue regeneration. Regen Med 2016; 10:461-79. [PMID: 26022765 DOI: 10.2217/rme.15.21] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
AIM To compare the odontogenic potential of human dental follicle cells (DFCs) and periodontal ligament cells (PDLCs). MATERIALS & METHODS In vitro and in vivo characterization studies of DFCs and PDLCs were performed comparatively. DFCs and PDLCs were subcutaneously implanted into the dorsum of mice for 8 weeks after combined with treated dentin matrix scaffolds respectively. RESULTS Proteomic analysis identified 32 differentially expressed proteins in DFCs and PDLCs. Examination of the harvested grafts showed PDLCs could form the dentin-like tissues as DFCs did. However, the structure of dentin tissues generated by DFCs was more complete. CONCLUSION PDLCs could contribute to regenerate dentin-like tissues in the inductive microenvironment of treated dentin matrix. DFCs presented more remarkable dentinogenic capability than PDLCs did.
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Affiliation(s)
- Ye Tian
- 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,2National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,3Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Ding Bai
- 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,3Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Weihua Guo
- 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,2National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,4Department of Pedodontics, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Jie Li
- 2National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,5College of Life Science, Sichuan University, Chengdu, P.R. China
| | - Jin Zeng
- 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,2National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Longqiang Yang
- 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,2National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,4Department of Pedodontics, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Zongting Jiang
- 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,2National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Lian Feng
- 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,2National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Mei Yu
- 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,2National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Weidong Tian
- 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China.,2National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
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Kato R, Takahashi K. Gene Expression of Semaphorin 7A During Osteogenic Differentiation in Human Dental Follicle Cells. J HARD TISSUE BIOL 2016. [DOI: 10.2485/jhtb.25.263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Ryoichi Kato
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo
| | - Kosuke Takahashi
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo
- Research Institute of Oral Science
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Role of lipid rafts in neuronal differentiation of dental pulp-derived stem cells. Exp Cell Res 2015; 339:231-40. [PMID: 26586565 DOI: 10.1016/j.yexcr.2015.11.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 11/10/2015] [Accepted: 11/12/2015] [Indexed: 01/14/2023]
Abstract
Human dental pulp-derived stem cells (hDPSCs) are characterized by a typical fibroblast-like morphology. They express specific markers for mesenchymal stem cells and are capable of differentiation into osteoblasts, adipoblasts and neurons in vitro. Previous studies showed that gangliosides are involved in the induction of early neuronal differentiation of hDPSCs. This study was undertaken to investigate the role of lipid rafts in this process. Lipid rafts are signaling microdomains enriched in glycosphingolipids, cholesterol, tyrosine kinase receptors, mono- or heterotrimeric G proteins and GPI-anchored proteins. We preliminary showed that established cells expressed multipotent mesenchymal stromal-specific surface antigens. Then, we analyzed the distribution of lipid rafts, revealing plasma membrane microdomains with GM2 and EGF-R enrichment. Following stimulation with EGF/bFGF, neuronal differentiation was observed. To analyze the functional role of lipid rafts in EGF/bFGF-induced hDPSCs differentiation, cells were preincubated with lipid raft affecting agents, i.e. [D]-PDMP or methyl-β-cyclodextrin. These compounds significantly prevented neuronal-specific antigen expression, as well as Akt and ERK 1/2 phosphorylation, induced by EGF/bFGF, indicating that lipid raft integrity is essential for EGF/bFGF-induced hDPSCs differentiation. These results suggest that lipid rafts may represent specific chambers, where multimolecular signaling complexes, including lipids (gangliosides, cholesterol) and proteins (EGF-R), play a role in hDPSCs differentiation.
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Abstract
Stem cells are cells specialized cell, capable of renewing themselves through cell division and can differentiate into multi-lineage cells. These cells are categorized as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells. Mesenchymal stem cells (MSCs) are adult stem cells which can be isolated from human and animal sources. Human MSCs (hMSCs) are the non-haematopoietic, multipotent stem cells with the capacity to differentiate into mesodermal lineage such as osteocytes, adipocytes and chondrocytes as well ectodermal (neurocytes) and endodermal lineages (hepatocytes). MSCs express cell surface markers like cluster of differentiation (CD)29, CD44, CD73, CD90, CD105 and lack the expression of CD14, CD34, CD45 and HLA (human leucocyte antigen)-DR. hMSCs for the first time were reported in the bone marrow and till now they have been isolated from various tissues, including adipose tissue, amniotic fluid, endometrium, dental tissues, umbilical cord and Wharton's jelly which harbours potential MSCs. hMSCs have been cultured long-term in specific media without any severe abnormalities. Furthermore, MSCs have immunomodulatory features, secrete cytokines and immune-receptors which regulate the microenvironment in the host tissue. Multilineage potential, immunomodulation and secretion of anti-inflammatory molecules makes MSCs an effective tool in the treatment of chronic diseases. In the present review, we have highlighted recent research findings in the area of hMSCs sources, expression of cell surface markers, long-term in vitro culturing, in vitro differentiation potential, immunomodulatory features, its homing capacity, banking and cryopreservation, its application in the treatment of chronic diseases and its use in clinical trials.
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31
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Liu J, Yu F, Sun Y, Jiang B, Zhang W, Yang J, Xu GT, Liang A, Liu S. Concise Reviews: Characteristics and Potential Applications of Human Dental Tissue-Derived Mesenchymal Stem Cells. Stem Cells 2015; 33:627-38. [PMID: 25447379 DOI: 10.1002/stem.1909] [Citation(s) in RCA: 233] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 10/21/2014] [Accepted: 11/07/2014] [Indexed: 12/16/2022]
Affiliation(s)
- Junjun Liu
- Department of Ophthalmology; Shanghai Tenth People's Hospital
| | - Fang Yu
- Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology; Tongji University; Shanghai People's Republic of China
| | - Yao Sun
- Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology; Tongji University; Shanghai People's Republic of China
| | - Beizhan Jiang
- Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology; Tongji University; Shanghai People's Republic of China
| | - Wenjun Zhang
- Translational Center for Stem Cell Research, Tongji Hospital; Tongji University School of Medicine; Shanghai People's Republic of China
| | - Jianhua Yang
- Department of Ophthalmology; Shanghai Tenth People's Hospital
| | - Guo-Tong Xu
- Department of Ophthalmology; Shanghai Tenth People's Hospital
| | - Aibin Liang
- Translational Center for Stem Cell Research, Tongji Hospital; Tongji University School of Medicine; Shanghai People's Republic of China
| | - Shangfeng Liu
- Department of Ophthalmology; Shanghai Tenth People's Hospital
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32
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Gosau M, Viale-Bouroncle S, Eickhoff H, Prateeptongkum E, Reck A, Götz W, Klingelhöffer C, Müller S, Morsczeck C. Evaluation of implant-materials as cell carriers for dental stem cells under in vitro conditions. Int J Implant Dent 2015; 1:2. [PMID: 27747624 PMCID: PMC5004001 DOI: 10.1186/s40729-014-0002-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 11/20/2014] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Dental stem cells in combination with implant materials may become an alternative to autologous bone transplants. For tissue engineering different types of soft and rigid implant materials are available, but little is known about the viability and the osteogenic differentiation of dental stem cells on these different types of materials. According to previous studies we proposed that rigid bone substitute materials are superior to soft materials for dental tissue engineering. METHODS We evaluated the proliferation, the induction of apoptosis and the osteogenic differentiation of dental stem/progenitor cells on a synthetic bone-like material and on an allograft product. The soft materials silicone and polyacrylamide (PA) were used for comparison. Precursor cells from the dental follicle (DFCs) and progenitor cells from the dental apical papilla of retained third molar tooth (dNC-PCs) were applied as dental stem cells in our study. RESULTS Both dental cell types attached and grew on rigid bone substitute materials, but they did not grow on soft materials. Moreover, rigid bone substitute materials only sustained the osteogenic differentiation of dental stem cells, although the allograft product induced apoptosis in both dental cell types. Remarkably, PA, silicone and the synthetic bone substitute material did not induce the apoptosis in dental cells. CONCLUSIONS Our work supports the hypothesis that bone substitute materials are suitable for dental stem cell tissue engineering. Furthermore, we also suggest that the induction of apoptosis by bone substitute materials may not impair the proliferation and the differentiation of dental stem cells.
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Affiliation(s)
- Martin Gosau
- Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.,Department of Oral and Maxillofacial Surgery, Paracelsus Medical University Nuernberg, Breslauer Str., 201, 90471, Nürnberg, Germany
| | - Sandra Viale-Bouroncle
- Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany
| | - Hannah Eickhoff
- Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany
| | - Esthera Prateeptongkum
- Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany
| | - Anja Reck
- Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany
| | - W Götz
- Department of Orthodontics, Oral Biology Laboratory, Dental Clinic, University of Bonn, Regina-Pacis-Weg 3, 53113, Bonn, Germany
| | - Christoph Klingelhöffer
- Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany
| | - Steffen Müller
- Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany
| | - Christian Morsczeck
- Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
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Marrelli M, Paduano F, Tatullo M. Human periapical cyst-mesenchymal stem cells differentiate into neuronal cells. J Dent Res 2015; 94:843-52. [PMID: 25672890 DOI: 10.1177/0022034515570316] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
It was recently reported that human periapical cysts (hPCys), a commonly occurring odontogenic cystic lesion of inflammatory origin, contain mesenchymal stem cells (MSCs) with the capacity for self-renewal and multilineage differentiation. In this study, periapical inflammatory cysts were compared with dental pulp to determine whether this tissue may be an alternative accessible tissue source of MSCs that retain the potential for neurogenic differentiation. Flow cytometry and immunofluorescence analysis indicated that hPCy-MSCs and dental pulp stem cells spontaneously expressed the neuron-specific protein β-III tubulin and the neural stem-/astrocyte-specific protein glial fibrillary acidic protein (GFAP) in their basal state before differentiation occurs. Furthermore, undifferentiated hPCy-MSCs showed a higher expression of transcripts for neuronal markers (β-III tubulin, NF-M, MAP2) and neural-related transcription factors (MSX-1, Foxa2, En-1) as compared with dental pulp stem cells. After exposure to neurogenic differentiation conditions (neural media containing epidermal growth factor [EGF], basic fibroblast growth factor [bFGF], and retinoic acid), the hPCy-MSCs showed enhanced expression of β-III tubulin and GFAP proteins, as well as increased expression of neurofilaments medium, neurofilaments heavy, and neuron-specific enolase at the transcript level. In addition, neurally differentiated hPCy-MSCs showed upregulated expression of the neural transcription factors Pitx3, Foxa2, Nurr1, and the dopamine-related genes tyrosine hydroxylase and dopamine transporter. The present study demonstrated for the first time that hPCy-MSCs have a predisposition toward the neural phenotype that is increased when exposed to neural differentiation cues, based on upregulation of a comprehensive set of proteins and genes that define neuronal cells. In conclusion, these results provide evidence that hPCy-MSCs might be another optimal source of neural/glial cells for cell-based therapies to treat neurologic diseases.
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Affiliation(s)
- M Marrelli
- Unit of Maxillofacial Surgery, Calabrodental, Crotone, Italy
| | - F Paduano
- Tecnologica Research Institute, Biomedical Section, Crotone, Italy
| | - M Tatullo
- Tecnologica Research Institute, Biomedical Section, Crotone, Italy
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Vollkommer T, Gosau M, Felthaus O, Reichert TE, Morsczeck C, Götz W. Genome-wide gene expression profiles of dental follicle stem cells. Acta Odontol Scand 2015; 73:93-100. [PMID: 25376664 DOI: 10.3109/00016357.2014.956143] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Dental stem cells (SCs) will be increasingly used for bone regeneration in the future. Recently, dental follicle cells (DFCs) from retained human third molars have been isolated and characterized as osteogenic progenitors. Although these results are promising for regenerative dentistry, molecular processes during osteogenic differentiation are not yet well understood. MATERIALS AND METHODS This study compared DFCs before and during osteogenic differentiation. ALP activity was measured and cells were stained with alizarin red. Real-time RT-PCRs for osteogenic markers were done. The genome-wide expression profile was evaluated using a microarray. RESULTS DFCs showed strong mineralization and increased expression of osteogenic marker genes during osteogenic differentiation. A microarray analysis showed regulated genes before and in the process of osteogenic differentiation (day 7). Several regulated genes in DFCs were associated with skeletal development. Bioinformatic analysis revealed a number of factors associated with dental follicle osteogenic differentiation. Osteogenic differentiation affected expression levels of the transcriptional regulators FOXC2 and ZNF219. CONCLUSION In conclusion, the results yielded new objectives for further studies on transcription factors like FOXC2 or ETV1 and their role in dental SCs during osteogenic differentiation.
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A therapeutic strategy for spinal cord defect: human dental follicle cells combined with aligned PCL/PLGA electrospun material. BIOMED RESEARCH INTERNATIONAL 2015; 2015:197183. [PMID: 25695050 PMCID: PMC4324737 DOI: 10.1155/2015/197183] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/25/2014] [Revised: 11/07/2014] [Accepted: 11/13/2014] [Indexed: 02/05/2023]
Abstract
Stem cell implantation has been utilized for the repair of spinal cord injury; however, it shows unsatisfactory performance in repairing large scale lesion of an organ. We hypothesized that dental follicle cells (DFCs), which possess multipotential capability, could reconstruct spinal cord defect (SCD) in combination with biomaterials. In the present study, mesenchymal and neurogenic lineage characteristics of human DFCs (hDFCs) were identified. Aligned electrospun PCL/PLGA material (AEM) was fabricated and it would not lead to cytotoxic reaction; furthermore, hDFCs could stretch along the oriented fibers and proliferate efficiently on AEM. Subsequently, hDFCs seeded AEM was transplanted to restore the defect in rat spinal cord. Functional observation was performed but results showed no statistical significance. The following histologic analyses proved that AEM allowed nerve fibers to pass through, and implanted hDFCs could express oligodendrogenic lineage maker Olig2 in vivo which was able to contribute to remyelination. Therefore, we concluded that hDFCs can be a candidate resource in neural regeneration. Aligned electrospun fibers can support spinal cord structure and induce cell/tissue polarity. This strategy can be considered as alternative proposals for the SCD regeneration studies.
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36
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Stem Cells from Dental Tissue for Regenerative Dentistry and Medicine. Regen Med 2015. [DOI: 10.1007/978-1-4471-6542-2_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Tomoki R, Ogura N, Takahashi K, Ito K, Kondoh T. MicroRNA-29 Family Suppresses Mineralization in Dental Follicle Cells. J HARD TISSUE BIOL 2015. [DOI: 10.2485/jhtb.24.23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Affiliation(s)
- Risa Tomoki
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo
| | - Naomi Ogura
- Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo
| | - Kosuke Takahashi
- Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo
| | - Ko Ito
- Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo
| | - Toshirou Kondoh
- Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo
- Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo
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Yoon HH, Min J, Shin N, Kim YH, Kim JM, Hwang YS, Suh JKF, Hwang O, Jeon SR. Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson's disease? Neural Regen Res 2014; 8:1190-200. [PMID: 25206413 PMCID: PMC4107610 DOI: 10.3969/j.issn.1673-5374.2013.13.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2012] [Accepted: 04/03/2013] [Indexed: 11/18/2022] Open
Abstract
Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.
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Affiliation(s)
- Hyung Ho Yoon
- Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Joongkee Min
- Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Nari Shin
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Hwan Kim
- Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN, USA
| | - Jin-Mo Kim
- Center for Bionics of Korea Institute of Science and Technology, Seoul, Korea
| | - Yu-Shik Hwang
- Department of Maxillofacial Biomedical Engineering, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, Korea
| | - Jun-Kyo Francis Suh
- Center for Bionics of Korea Institute of Science and Technology, Seoul, Korea
| | - Onyou Hwang
- Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Ryong Jeon
- Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Lee JH, Um S, Song IS, Kim HY, Seo BM. Neurogenic differentiation of human dental stem cells in vitro. J Korean Assoc Oral Maxillofac Surg 2014; 40:173-80. [PMID: 25247147 PMCID: PMC4170666 DOI: 10.5125/jkaoms.2014.40.4.173] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Revised: 06/27/2014] [Accepted: 07/01/2014] [Indexed: 12/13/2022] Open
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.
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Affiliation(s)
- Joo-Hee Lee
- Biotooth Engineering Lab, Department of Oral and Maxillofacial Surgery and Craniomaxillofacial Life Science, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea
| | - Soyoun Um
- Biotooth Engineering Lab, Department of Oral and Maxillofacial Surgery and Craniomaxillofacial Life Science, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea. ; Dental Regenerative Biotechnology, Department of Dental Science, School of Dentistry, Seoul National University, Seoul, Korea
| | - In-Seok Song
- Biotooth Engineering Lab, Department of Oral and Maxillofacial Surgery and Craniomaxillofacial Life Science, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea. ; Division of Oral and Maxillofacial Surgery, Department of Dentistry, Korea University Anam Hospital, Seoul, Korea
| | - Hui Young Kim
- Biotooth Engineering Lab, Department of Oral and Maxillofacial Surgery and Craniomaxillofacial Life Science, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea
| | - Byoung Moo Seo
- Biotooth Engineering Lab, Department of Oral and Maxillofacial Surgery and Craniomaxillofacial Life Science, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea
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Laminin regulates the osteogenic differentiation of dental follicle cells via integrin-α2/-β1 and the activation of the FAK/ERK signaling pathway. Cell Tissue Res 2014; 357:345-54. [PMID: 24788823 DOI: 10.1007/s00441-014-1869-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Accepted: 03/05/2014] [Indexed: 10/25/2022]
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Neural crest-derived dental stem cells--where we are and where we are going. J Dent 2014; 42:1043-51. [PMID: 24769107 DOI: 10.1016/j.jdent.2014.04.007] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Revised: 04/11/2014] [Accepted: 04/14/2014] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVES There are five types of post-natal human dental stem cells that have been identified, isolated and characterized. Here, we review the information available on dental stem cells as well as their potential applications in dentistry, regenerative medicine and the development of other therapeutic approaches. DATA Data pertinent to dental stem cells and their applications, published in peer-reviewed journals from 1982 to 2013 in English were reviewed. SOURCES Sources were retrieved from PubMed databases as well as related references that the electronic search yielded. STUDY SELECTION Manuscripts describing the origin, retrieval, characterization and application of dental stem cells were obtained and reviewed. CONCLUSIONS Dental stem cell populations present properties similar to those of mesenchymal stem cells, such as the ability to self-renew and the potential for multilineage differentiation. While they have greater capacity to give rise to odontogenic cells and regenerate dental pulp and periodontal tissue, they have the capacity to differentiate into all three germ line cells, proving that a population of pluripotent stem cells exists in the dental tissues. CLINICAL SIGNIFICANCE Dental stem cells have the capacity to differentiate into endoderm, mesoderm and ectoderm tissues. Consequently they do not only have applications in dentistry, but also neurodegenerative and ischemic diseases, diabetes research, bone repair, and other applications in the field of tissue regeneration.
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Chamila Prageeth Pandula P, Samaranayake L, Jin L, Zhang C. Periodontal ligament stem cells: an update and perspectives. ACTA ACUST UNITED AC 2014; 5:81-90. [DOI: 10.1111/jicd.12089] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2013] [Accepted: 11/23/2013] [Indexed: 12/12/2022]
Affiliation(s)
| | - L.P. Samaranayake
- Department of Oral Biosciences; Faculty of Dentistry; The University of Hong Kong; Hong Kong China
| | - L.J. Jin
- Department of Periodontology; Faculty of Dentistry; The University of Hong Kong; Hong Kong China
| | - Chengfei Zhang
- Department of Comprehensive Dental Care; Faculty of Dentistry; The University of Hong Kong; Hong Kong China
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Wada N, Maeda H, Hasegawa D, Gronthos S, Bartold PM, Menicanin D, Fujii S, Yoshida S, Tomokiyo A, Monnouchi S, Akamine A. Semaphorin 3A induces mesenchymal-stem-like properties in human periodontal ligament cells. Stem Cells Dev 2014; 23:2225-36. [PMID: 24380401 DOI: 10.1089/scd.2013.0405] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Periodontal ligament stem cells (PDLSCs) have recently been proposed as a novel option in periodontal regenerative therapy. However, one of the issues is the difficulty of stably generating PDLSCs because of the variation of stem cell potential between donors. Here, we show that Semaphorin 3A (Sema3A) can induce mesenchymal-stem-like properties in human periodontal ligament (PDL) cells. Sema3A expression was specifically observed in the dental follicle during tooth development and in parts of mature PDL tissue in rodent tooth and periodontal tissue. Sema3A expression levels were found to be higher in multipotential human PDL cell clones compared with low-differentiation potential clones. Sema3A-overexpressing PDL cells exhibited an enhanced capacity to differentiate into both functional osteoblasts and adipocytes. Moreover, PDL cells treated with Sema3A only at the initiation of culture stimulated osteogenesis, while Sema3A treatment throughout the culture had no effect on osteogenic differentiation. Finally, Sema3A-overexpressing PDL cells upregulated the expression of embryonic stem cell markers (NANOG, OCT4, and E-cadherin) and mesenchymal stem cell markers (CD73, CD90, CD105, CD146, and CD166), and Sema3A promoted cell division activity of PDL cells. These results suggest that Sema3A may possess the function to convert PDL cells into mesenchymal-stem-like cells.
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Affiliation(s)
- Naohisa Wada
- 1 Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
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Chen X, Zhang T, Shi J, Xu P, Gu Z, Sandham A, Yang L, Ye Q. Notch1 signaling regulates the proliferation and self-renewal of human dental follicle cells by modulating the G1/S phase transition and telomerase activity. PLoS One 2013; 8:e69967. [PMID: 23922876 PMCID: PMC3726724 DOI: 10.1371/journal.pone.0069967] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2013] [Accepted: 06/13/2013] [Indexed: 01/25/2023] Open
Abstract
Multipotent human dental follicle cells (HDFCs) have been intensively studied in periodontal regeneration research, yet the role of Notch1 in HDFCs has not been fully understood. The aim of the current study is to explore the role of Notch1 signaling in HDFCs self-renewal and proliferation. HDFCs were obtained from the extracted wisdom teeth from adolescent patients. Regulation of Notch1 signaling in the HDFCs was achieved by overexpressing the exogenous intracellular domain of Notch1 (ICN1) or silencing Notch1 by shRNA. The regulatory effects of Notch1 on HDFC proliferation, cell cycle distribution and the expression of cell cycle regulators were investigated through various molecular technologies, including plasmid construction, retrovirus preparation and infection, qRT-PCR, western blot, RBP-Jk luciferase reporter and cell proliferation assay. Our data clearly show that constitutively activation of Notch1 stimulates the HDFCs proliferation while inhibition of the Notch1 suppresses their proliferation in vitro. In addition, the HDFCs proliferation is associated with the increased expression of cell cycle regulators, e.g. cyclin D1, cyclin D2, cyclin D3, cyclin E1, CDK2, CDK4, CDK6, and SKP2 and the decreased expression of p27 (kip1). Moreover, our data show that the G1/S phase transition (indicating proliferation) and telomerase activity (indicating self-renewal) can be enhanced by overexpression of ICN1 but halted by inhibition of Notch1. Together, the current study provides evidence for the first time that Notch1 signaling regulates the proliferation and self-renewal capacity of HDFCs through modulation of the G1/S phase transition and the telomerase activity.
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Affiliation(s)
- Xuepeng Chen
- Department of Orthodontics, Hospital of Stomatology, Zhejiang University, Hangzhou, Zhejiang, China
- * E-mail: (XC); (QY)
| | - Tianhou Zhang
- Department of Stomatology, Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jiejun Shi
- Department of Orthodontics, Hospital of Stomatology, Zhejiang University, Hangzhou, Zhejiang, China
| | - Ping Xu
- Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Zexu Gu
- Department of Orthodontics, Qindu Stomatological College, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Andrew Sandham
- Department of Orthodontics, School of Medicine and Dentistry, James Cook University, Cairns, Queensland, Australia
| | - Lei Yang
- Department of Orthodontics, Qindu Stomatological College, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Qingsong Ye
- Department of Orthodontics, School of Medicine and Dentistry, James Cook University, Cairns, Queensland, Australia
- * E-mail: (XC); (QY)
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Guo L, Li J, Qiao X, Yu M, Tang W, Wang H, Guo W, Tian W. Comparison of odontogenic differentiation of human dental follicle cells and human dental papilla cells. PLoS One 2013; 8:e62332. [PMID: 23620822 PMCID: PMC3631153 DOI: 10.1371/journal.pone.0062332] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2012] [Accepted: 03/20/2013] [Indexed: 02/05/2023] Open
Abstract
Classical tooth development theory suggests that dental papilla cells (DPCs) are the precursor cells of odontoblasts, which are responsible for dentin development. However, our previous studies have indicated that dental follicle cells (DFCs) can differentiate into odontoblasts. To further our understanding of tooth development, and the differences in dentinogenesis between DFCs and DPCs, the odontogenic differentiation of DFCs and DPCs was characterized in vitro and in vivo. DFCs and DPCs were individually combined with treated dentin matrix (TDM) before they were subcutaneously implanted into the dorsum of mice for 8 weeks. Results showed that 12 proteins were significantly differential, and phosphoserine aminotransferase 1 (PSAT1), Isoform 2 of hypoxia-inducible factor 1-alpha (HIF1A) and Isoform 1 of annexin A2 (ANXA2), were the most significantly differential proteins. These proteins are related to regulation of bone balance, angiogenesis and cell survival in an anoxic environment. Both DFCs and DPCs express odontogenic, neurogenic and peridontogenic markers. Histological examination of the harvested grafts showed that both DFCs and DPCs form pulp-dentin/cementum-periodentium-like tissues in vivo. Hence, DFCs and DPCs have similar odontogenic differentiation potential in the presence of TDM. However, differences in glucose and amino acid metabolism signal transduction and protein synthesis were observed for the two cell types. This study expands our understanding on tooth development, and provides direct evidence for the use of alternative cell sources in tooth regeneration.
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Affiliation(s)
- Lijuan Guo
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
- Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Jie Li
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
- College of Life Science, Sichuan University, Chengdu, P.R. China
| | - Xiangchen Qiao
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Mei Yu
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Wei Tang
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
- Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Hang Wang
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
- Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Weihua Guo
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
- Department of Pedodontics, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
- * E-mail: (WG); (WT)
| | - Weidong Tian
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
- Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
- * E-mail: (WG); (WT)
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Iwai S, Kuyama K, Kuboyama N, Takiguchi S, Ogura N, Yamamoto H, Kondoh T. Osteogenic Potential of Human Dental Follicle Cells on Rat Calvaria. J HARD TISSUE BIOL 2013. [DOI: 10.2485/jhtb.22.95] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Abstract
A stem-cell-based therapy could be the ultimate strategy for the regeneration of degenerated nervous tissues. While neural progenitor cells are limited, the generation of functional nervous tissue cells from non-neural somatic cells (for example, dental stem cells) is highly desired. The recent publication in Stem Cell Research and Therapy by Huang and colleagues is an interesting contribution to this topic. The present commentary puts this paper in context with contemporary reports about (transgene-free) induced pluripotent stem cells and neurogenic differentiation.
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Viale-Bouroncle S, Gosau M, Küpper K, Möhl C, Brockhoff G, Reichert TE, Schmalz G, Ettl T, Morsczeck C. Rigid matrix supports osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHED). Differentiation 2012; 84:366-70. [PMID: 23142732 DOI: 10.1016/j.diff.2012.08.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2012] [Revised: 07/17/2012] [Accepted: 08/24/2012] [Indexed: 01/09/2023]
Abstract
Stem cell fate can be induced by the grade of stiffness of the extracellular matrix, depending on the developed tissue or complex tissues. For example, a rigid extracellular matrix induces the osteogenic differentiation in bone marrow derived mesenchymal stem cells (MSCs), while a softer surface induces the osteogenic differentiation in dental follicle cells (DFCs). To determine whether differentiation of ectomesenchymal dental precursor cells is supported by similar grades of extracellular matrices (ECMs) stiffness, we examined the influence of the surface stiffness on the proliferation and osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHED). Cell proliferation of SHED was significantly decreased on cell culture surfaces with a muscle-like stiffness. A dexamethasone-based differentiation medium induced the osteogenic differentiation of SHED on substrates of varying mechanical stiffness. Here, the hardest surface improved the induction of osteogenic differentiation in comparison to that with the softest stiffness. In conclusion, our study showed that the osteogenic differentiation of ectomesenchymal dental precursor cells SHED and DFCs are not supported by similar grades of ECM stiffness.
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Hynes K, Menicanin D, Gronthos S, Bartold PM. Clinical utility of stem cells for periodontal regeneration. Periodontol 2000 2012; 59:203-27. [PMID: 22507067 DOI: 10.1111/j.1600-0757.2012.00443.x] [Citation(s) in RCA: 169] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal-regenerative potential of stem cells. We considered and described the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow-derived mesenchymal stem cells and the main dental-derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.
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