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Chuang EY, Lin YC, Huang YM, Chen CH, Yeh YY, Rethi L, Chou YJ, Jheng PR, Lai JM, Chiang CJ, Wong CC. Biofunctionalized hydrogel composed of genipin-crosslinked gelatin/hyaluronic acid incorporated with lyophilized platelet-rich fibrin for segmental bone defect repair. Carbohydr Polym 2024; 339:122174. [PMID: 38823938 DOI: 10.1016/j.carbpol.2024.122174] [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] [Received: 03/01/2024] [Revised: 04/07/2024] [Accepted: 04/16/2024] [Indexed: 06/03/2024]
Abstract
Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.
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Affiliation(s)
- Er-Yuan Chuang
- Graduate Institute of Biomedical Materials and Tissue Engineering, School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan; Cell Physiology and Molecular Image Research Center, Taipei Medical University-Wan Fang Hospital, Taipei 11696, Taiwan; Precision Medicine and Translational Cancer Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Yi-Cheng Lin
- Department of Orthopedics, Taipei Medical University Shuang Ho Hospital, New Taipei City 23561, Taiwan; Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Yu-Min Huang
- Department of Orthopedics, Taipei Medical University Shuang Ho Hospital, New Taipei City 23561, Taiwan; Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Chih-Hwa Chen
- Graduate Institute of Biomedical Materials and Tissue Engineering, School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan; Department of Orthopedics, Taipei Medical University Shuang Ho Hospital, New Taipei City 23561, Taiwan; Taipei Medical University Research Center of Biomedical Devices Prototyping Production, Taipei 11031, Taiwan; School of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan; School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yi-Yen Yeh
- Department of Orthopedics, Taipei Medical University Shuang Ho Hospital, New Taipei City 23561, Taiwan
| | - Lekha Rethi
- Department of Orthopedics, Taipei Medical University Shuang Ho Hospital, New Taipei City 23561, Taiwan
| | - Yu-Jen Chou
- Department of Mechanical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan
| | - Pei-Ru Jheng
- Graduate Institute of Biomedical Materials and Tissue Engineering, School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
| | - Jen-Ming Lai
- Department of Orthopedic Surgery, Woodlands Health, 768024, Singapore
| | - Chang-Jung Chiang
- Department of Orthopedics, Taipei Medical University Shuang Ho Hospital, New Taipei City 23561, Taiwan; Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Taipei Medical University Research Center of Biomedical Devices Prototyping Production, Taipei 11031, Taiwan
| | - Chin-Chean Wong
- Department of Orthopedics, Taipei Medical University Shuang Ho Hospital, New Taipei City 23561, Taiwan; Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Taipei Medical University Research Center of Biomedical Devices Prototyping Production, Taipei 11031, Taiwan; International PhD Program for Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
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Tatsis D, Vasalou V, Kotidis E, Anestiadou E, Grivas I, Cheva A, Koliakos G, Venetis G, Pramateftakis MG, Ouzounidis N, Angelopoulos S. The Combined Use of Platelet-Rich Plasma and Adipose-Derived Mesenchymal Stem Cells Promotes Healing. A Review of Experimental Models and Future Perspectives. Biomolecules 2021; 11:1403. [PMID: 34680036 PMCID: PMC8533225 DOI: 10.3390/biom11101403] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/15/2021] [Accepted: 09/17/2021] [Indexed: 11/16/2022] Open
Abstract
Wound healing and tissue regeneration are a field of clinical medicine presenting high research interest, since various local and systematic factors can inhibit these processes and lead to an inferior result. New methods of healing enhancement constantly arise, which, however, require experimental validation before their establishment in everyday practice. Platelet-rich plasma (PRP) is a well-known autologous factor that promotes tissue healing in various surgical defects. PRP derives from the centrifugation of peripheral blood and has a high concentration of growth factors that promote healing. Recently, the use of adipose-derived mesenchymal stem cells (ADMSCs) has been thoroughly investigated as a form of wound healing enhancement. ADMSCs are autologous stem cells deriving from fat tissue, with a capability of differentiation in specific cells, depending on the micro-environment that they are exposed to. The aim of the present comprehensive review is to record the experimental studies that have been published and investigate the synergistic use of PRP and ADMSC in animal models. The technical aspects of experimentations, as well as the major results of each study, are discussed. In addition, the limited clinical studies including humans are also reported. Future perspectives are discussed, along with the limitations of current studies on the long-term follow up needed on efficacy and safety.
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Affiliation(s)
- Dimitris Tatsis
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
- Oral and Maxillofacial Surgery Department, School of Dentistry, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece;
| | - Varvara Vasalou
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
| | - Efstathios Kotidis
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
| | - Elissavet Anestiadou
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
| | - Ioannis Grivas
- Laboratory of Anatomy, Histology & Embryology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Angeliki Cheva
- Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Georgios Koliakos
- Department of Biochemistry, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Gregory Venetis
- Oral and Maxillofacial Surgery Department, School of Dentistry, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece;
| | - Manousos-George Pramateftakis
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
| | - Nikolaos Ouzounidis
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
| | - Stamatis Angelopoulos
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
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Egido-Moreno S, Valls-Roca-Umbert J, Céspedes-Sánchez JM, López-López J, Velasco-Ortega E. Clinical Efficacy of Mesenchymal Stem Cells in Bone Regeneration in Oral Implantology. Systematic Review and Meta-Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18030894. [PMID: 33494139 PMCID: PMC7908266 DOI: 10.3390/ijerph18030894] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/12/2021] [Accepted: 01/17/2021] [Indexed: 11/27/2022]
Abstract
In bone regeneration, obtaining a vital bone as similar as possible to native bone is sought. This review aimed to evaluate the efficacy of stem cells in maxillary bone regeneration for implant rehabilitation and to review the different techniques for obtaining and processing these cells. A systematic review and meta-analysis were performed using the Pubmed/Medline (NCBI), Cochrane, Scielo, and Scopus databases, without restriction on the publication date. The following Mesh terms were used, combined by the Boolean operator “AND”: “dental implants” AND “stem cells” AND “bioengineering”. Applying inclusion and exclusion criteria, five articles were obtained and three were added after manual search. The results from the meta-analysis (18 patients) did not provide significant differences despite the percentage of bone formed in the maxillary sinus, favoring the stem cell group, and the analysis of the percentage of residual Bio-Oss® showed results favoring the control group. Stem cell regeneration usually shows positive vascular and viable bone formation. In conclusion, using mesenchymal stem cells in bone regeneration provides benefits in the quality of bone, similar or even superior to autologous bone, all this through a minimally invasive procedure.
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Affiliation(s)
- Sonia Egido-Moreno
- Department of Odontoestomatology, Faculty of Medicine and Health Sciences, School of Dentistry, University of Barcelona—Campus Bellvitge, 08907 Barcelona, Spain; (S.E.-M.); (J.V.-R.-U.); (J.M.C.-S.)
| | - Joan Valls-Roca-Umbert
- Department of Odontoestomatology, Faculty of Medicine and Health Sciences, School of Dentistry, University of Barcelona—Campus Bellvitge, 08907 Barcelona, Spain; (S.E.-M.); (J.V.-R.-U.); (J.M.C.-S.)
| | - Juan Manuel Céspedes-Sánchez
- Department of Odontoestomatology, Faculty of Medicine and Health Sciences, School of Dentistry, University of Barcelona—Campus Bellvitge, 08907 Barcelona, Spain; (S.E.-M.); (J.V.-R.-U.); (J.M.C.-S.)
| | - José López-López
- Department of Odontoestomatology, Faculty of Medicine and Health Sciences, School of Dentistry, University of Barcelona—Campus Bellvitge, 08907 Barcelona, Spain; (S.E.-M.); (J.V.-R.-U.); (J.M.C.-S.)
- Correspondence: ; Tel.: +34-606-45-73-62
| | - Eugenio Velasco-Ortega
- Department of Stomatology, Faculty of Dentistry, University of Seville, 41013 Seville, Spain;
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Nizami MZI, Nishina Y. Recent Advances in Stem Cells for Dental Tissue Engineering. ENGINEERING MATERIALS FOR STEM CELL REGENERATION 2021:281-324. [DOI: 10.1007/978-981-16-4420-7_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Nakano K, Kubo H, Nakajima M, Honda Y, Hashimoto Y. Bone Regeneration Using Rat-Derived Dedifferentiated Fat Cells Combined with Activated Platelet-Rich Plasma. MATERIALS 2020; 13:ma13225097. [PMID: 33198129 PMCID: PMC7697578 DOI: 10.3390/ma13225097] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 11/07/2020] [Accepted: 11/09/2020] [Indexed: 12/23/2022]
Abstract
Bone regeneration using mesenchymal stem cells has several limitations. We investigated adipose-derived dedifferentiated fat (DFAT) cells as an alternative, and evaluated their cell proliferation rate, osteoblast differentiation, and bone regeneration ability in combination with activated platelet-rich plasma (aPRP). Rat DFATs and aPRP were isolated using ceiling culture and centrifugation, respectively. The cell proliferation rate was measured, and the cells were cultured in an osteoblast differentiation medium under varying concentrations of aPRP for 21 days and stained with Alizarin red. Gene expression was evaluated using real time polymerase chain reaction. Critical defects were implanted with DFAT seeded gelatin sponges under aPRP, and four weeks later, the bone regeneration ability was evaluated using micro-computed tomography and hematoxylin-eosin staining. The cell proliferation rate was significantly increased by the addition of aPRP. Alizarin red staining was positive 21 days after the start of induction, with significantly higher Runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression levels than those in the controls. A 9 mm critical defect was largely closed (60.6%) after four weeks of gelatin sponge implantation with DFAT and aPRP. Therefore, materials combining DFAT cells and aPRP may be an effective approach for bone regeneration. Further research is needed to explore the long-term effects of these materials.
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Affiliation(s)
- Kosuke Nakano
- Graduate School of Dentistry Department of Oral and Maxillofacial Surgery, Osaka Dental University, 8-1, Kuzuha-hanazono-cho, Hirakata City, Osaka 573-1121, Japan;
| | - Hirohito Kubo
- Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, 1-5-17, Otemae, Chuo-ku, Osaka City, Osaka 540-0008, Japan; (H.K.); (M.N.)
| | - Masahiro Nakajima
- Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, 1-5-17, Otemae, Chuo-ku, Osaka City, Osaka 540-0008, Japan; (H.K.); (M.N.)
| | - Yoshitomo Honda
- Institute of Dental Research, Osaka Dental University, 8-1, Kuzuha-hanazono-cho, Hirakata City, Osaka 573-1121, Japan;
| | - Yoshiya Hashimoto
- Department of Biomaterials, Osaka Dental University, 8-1, Kuzuha-hanazono-cho, Hirakata City, Osaka 573-1121, Japan
- Correspondence: ; Tel.: +81-7264-3016
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Ledesma-Martínez E, Mendoza-Núñez VM, Santiago-Osorio E. Mesenchymal Stem Cells for Periodontal Tissue Regeneration in Elderly Patients. J Gerontol A Biol Sci Med Sci 2020; 74:1351-1358. [PMID: 30289440 DOI: 10.1093/gerona/gly227] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Indexed: 12/16/2022] Open
Abstract
Mesenchymal stem cell (MSC) grafting is a highly promising alternative strategy for periodontal regeneration in periodontitis, which is one of the primary causes of tooth loss in the elderly. However, aging progressively decreases the proliferative and differentiation potential of MSCs and diminishes their regenerative capacity, which represents a limiting factor for their endogenous use in elderly patients. Therefore, tissue regeneration therapy with MSCs in this age group may require a cellular source without the physiological limitations that MSCs exhibit in aging. In this sense, exogenous or allogeneic MSCs could have a better chance of success in regenerating periodontal tissue in elderly patients. This review examines and synthesizes recent data in support of the use of MSCs for periodontal regenerative therapy in patients. Additionally, we analyze the progress of the therapeutic use of exogenous MSCs in humans.
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Affiliation(s)
- Edgar Ledesma-Martínez
- Haematopoiesis and Leukaemia Laboratory, Research Unit on Cell Differentiation and Cancer, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Edelmiro Santiago-Osorio
- Haematopoiesis and Leukaemia Laboratory, Research Unit on Cell Differentiation and Cancer, National Autonomous University of Mexico, Mexico City, Mexico
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Shanbhag S, Suliman S, Pandis N, Stavropoulos A, Sanz M, Mustafa K. Cell therapy for orofacial bone regeneration: A systematic review and meta-analysis. J Clin Periodontol 2019; 46 Suppl 21:162-182. [DOI: 10.1111/jcpe.13049] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 10/17/2018] [Accepted: 10/26/2018] [Indexed: 12/15/2022]
Affiliation(s)
- Siddharth Shanbhag
- Department of Clinical Dentistry; Center for Clinical Dental Research; University of Bergen; Bergen Norway
| | - Salwa Suliman
- Department of Clinical Dentistry; Center for Clinical Dental Research; University of Bergen; Bergen Norway
| | - Nikolaos Pandis
- Department of Orthodontics and Dentofacial Orthopedics; University of Bern; Bern Switzerland
| | - Andreas Stavropoulos
- Department of Periodontology; Faculty of Odontology; Malmö University; Malmö Sweden
| | - Mariano Sanz
- Section of Periodontology; Faculty of Odontology; University Complutense of Madrid; Madrid Spain
| | - Kamal Mustafa
- Department of Clinical Dentistry; Center for Clinical Dental Research; University of Bergen; Bergen Norway
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Adipogenic Mesenchymal Stem Cells and Hyaluronic Acid as a Cellular Compound for Bone Tissue Engineering. J Craniofac Surg 2019; 30:777-783. [DOI: 10.1097/scs.0000000000005392] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
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Shimizu S, Tsuchiya S, Hirakawa A, Kato K, Ando M, Mizuno M, Osugi M, Okabe K, Katagiri W, Hibi H. Design of a Randomized Controlled Clinical Study of tissue-engineered osteogenic materials using bone marrow-derived mesenchymal cells for Maxillomandibular bone defects in Japan: the TEOM study protocol. BMC Oral Health 2019; 19:69. [PMID: 31039763 PMCID: PMC6492409 DOI: 10.1186/s12903-019-0753-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 04/03/2019] [Indexed: 01/01/2023] Open
Abstract
Background Maxillomandibular bone defects arise from maxillofacial injury or tumor/cyst removal. While the standard therapy for bone regeneration is transplantation with autologous bone or artificial bone, these therapies are still unsatisfactory. Autologous bone harvesting is invasive and occasionally absorbed at the implanted site. The artificial bone takes a long time to ossify and it often gets infected. Therefore, we have focused on regenerative therapy consisting of autologous bone marrow-derived mesenchymal cells (BM-MSCs), which decreases the burden on patients. Based on our previous research in patients with maxillomandibular bone defects or alveolar bone atrophy using a mixture of BM-MSCs, platelet-rich plasma (PRP), thrombin, and calcium, we confirmed the efficacy and acceptable safety profile of this treatment. In this investigator-initiated clinical study (the TEOM study), we intended to add β-tricalcium phosphate (β-TCP) owing to large defect with patients. The TEOM study aimed to evaluate the efficacy and safety of bone regeneration using mixtures of BM-MSCs in patients with bone defects resulting from maxillofacial injury, and tumor/cyst removal in the maxillomandibular region. Methods The TEOM study is an open-label, single-center, randomized controlled study involving a total of 83 segments by the Fédération Dentaire Internationale numbering system in maxillomandibular bone defects that comprise over 1/3 of the maxillomandibular area with a remaining bone height of ≤10 mm. The primary endpoint is rate of procedure sites with successful bone regeneration defined as a computed tomography (CT) value of more than 400 and a bone height of more than 10 mm. Our specific hypothesis is that the number of required regions was calculated assuming that the rate of procedure sites with successful bone regeneration is similar and the non-inferiority margin is 15.0%. Discussion The TEOM study is the first randomized controlled study of regenerative treatment using BM-MSCs for large maxillomandibular bone defects. We will evaluate the efficacy and safety in this study to provide an exploratory basis for the necessity of BM-MSCs for these patients. Trial registration This trial was registered at the University Hospital Medical information Network Clinical Trials Registry (UMIN-CTR Unique ID: UMIN000020398; Registration Date: Jan 15, 2016; URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016543).
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Affiliation(s)
- Shinobu Shimizu
- Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8560, Japan
| | - Shuhei Tsuchiya
- Department of Oral and Maxillofacial Surgery, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8560, Japan.
| | - Akihiro Hirakawa
- Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8560, Japan.,Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Katsuyoshi Kato
- Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8560, Japan
| | - Masahiko Ando
- Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8560, Japan
| | - Masaaki Mizuno
- Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8560, Japan
| | - Masashi Osugi
- Department of Oral and Maxillofacial Surgery, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8560, Japan.,Department of Oral and Maxillofacial Surgery, Fujieda Heisei Memorial Hospital, 123-1 Mizukami, Fujieda, Shizuoka, 426-8662, Japan
| | - Kazuto Okabe
- Department of Oral and Maxillofacial Surgery, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8560, Japan
| | - Wataru Katagiri
- Department of Oral and Maxillofacial Surgery, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8560, Japan.,Division of Reconstructive Surgery and Oral and Maxillofacial Region, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan
| | - Hideharu Hibi
- Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
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Niño-Sandoval TC, Vasconcelos BC, D Moraes SL, A Lemos CA, Pellizzer EP. Efficacy of stem cells in maxillary sinus floor augmentation: systematic review and meta-analysis. Int J Oral Maxillofac Surg 2019; 48:1355-1366. [PMID: 29759309 DOI: 10.1016/j.ijom.2018.04.022] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2017] [Revised: 02/17/2018] [Accepted: 04/24/2018] [Indexed: 12/21/2022]
Abstract
The aim of this review was to test the hypothesis of no difference in the efficacy of bone regeneration when using stem cells in maxillary sinus floor augmentation surgery in comparison to other grafts. Nine randomized clinical trials and one follow-up study involving human subjects were identified through a search of the PubMed/MEDLINE, Scopus, Cochrane, and Web of Science databases, supplemented by a hand search. No significant difference between groups was found for the implant survival rate, increase in bone height, marginal bone loss following implant placement, or new bone formation. With regard to the residual bone graft, an effect favouring the graft group at 3-4months (P=0.001) and favouring the stem cell group at 6months (P=0.01) was found. Analyses of the subgroup in which the BMAC system extraction method was used in combination with Bio-Oss, revealed no difference in new bone formation; however, the results for residual bone graft at 3months favoured the control graft (Bio-Oss) (P=0.01), but at 6months favoured the stem cells (Bio-Oss+BMAC system) (P=0.01). Based on all findings, the use of stem cells does not contribute significantly to greater implant survival rates or the efficacy of bone regeneration following sinus lift procedures.
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Affiliation(s)
- T C Niño-Sandoval
- Department of Oral and Maxillofacial Surgery, University of Pernambuco, Camaragibe, Pernambuco, Brazil
| | - B C Vasconcelos
- Department of Oral and Maxillofacial Surgery, University of Pernambuco, Camaragibe, Pernambuco, Brazil.
| | - S L D Moraes
- Department of Prosthodontics, University of Pernambuco, Recife, Pernambuco, Brazil
| | - C A A Lemos
- Department of Prosthodontics and Dental Materials, Araçatuba Dental School, São Paulo State University - UNESP, Araçatuba, São Paulo, Brazil
| | - E P Pellizzer
- Department of Prosthodontics and Dental Materials, Araçatuba Dental School, São Paulo State University - UNESP, Araçatuba, São Paulo, Brazil
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Stem Cells in Dentistry: Types of Intra- and Extraoral Tissue-Derived Stem Cells and Clinical Applications. Stem Cells Int 2018; 2018:4313610. [PMID: 30057624 PMCID: PMC6051054 DOI: 10.1155/2018/4313610] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 04/05/2018] [Accepted: 06/07/2018] [Indexed: 12/13/2022] Open
Abstract
Stem cells are undifferentiated cells, capable of renewing themselves, with the capacity to produce different cell types to regenerate missing tissues and treat diseases. Oral facial tissues have been identified as a source and therapeutic target for stem cells with clinical interest in dentistry. This narrative review report targets on the several extraoral- and intraoral-derived stem cells that can be applied in dentistry. In addition, stem cell origins are suggested in what concerns their ability to differentiate as well as their particular distinguishing quality of convenience and immunomodulatory for regenerative dentistry. The development of bioengineered teeth to replace the patient's missing teeth was also possible because of stem cell technologies. This review will also focus our attention on the clinical application of stem cells in dentistry. In recent years, a variety of articles reported the advantages of stem cell-based procedures in regenerative treatments. The regeneration of lost oral tissue is the target of stem cell research. Owing to the fact that bone imperfections that ensue after tooth loss can result in further bone loss which limit the success of dental implants and prosthodontic therapies, the rehabilitation of alveolar ridge height is prosthodontists' principal interest. The development of bioengineered teeth to replace the patient's missing teeth was also possible because of stem cell technologies. In addition, a “dental stem cell banking” is available for regenerative treatments in the future. The main features of stem cells in the future of dentistry should be understood by clinicians.
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Correia F, Pozza DH, Gouveia S, Felino A, Faria E Almeida R. The applications of regenerative medicine in sinus lift procedures: A systematic review. Clin Implant Dent Relat Res 2018; 20:229-242. [PMID: 29205768 DOI: 10.1111/cid.12561] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 10/25/2017] [Accepted: 11/01/2017] [Indexed: 01/13/2023]
Abstract
BACKGROUND Findings in regenerative medicine applied to the sinus lift procedures. PURPOSE Evaluate the effectiveness of regenerative medicine in sinus lift. MATERIALS AND METHODS An extensive search for manuscripts were performed by using different combinations of keywords and MeSH terms (Pub-med; Embase; Scopus; Web of Science Core Collection; Medline; Current Contents Connect; Derwent Innovations Index; Scielo Citation Index; Cochrane library). The full text selected articles are written in English, Portuguese, Spanish, Italian, German, or French, and published until 28 of November 2016. Inclusion criteria were: implant osteointegration, radiographic, histologic, and/or histomorphometric analysis, clinical studies in humans using of regenerative medicine. This systematic review was performed by selecting only randomized controlled clinical trials and controlled clinical trials. RESULTS Eighteen published studies (11 CT and 7 RCT) were considered eligible for inclusion in the present systematic review. These studies demonstrated considerable variation of biomaterial and cell technics used, study design, sinus lift technic, outcomes, follow-up, and results. CONCLUSION Only few studies have demonstrated potential of regenerative medicine in sinus lift; further randomized clinical trials are needed to achieve more accurate results.
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Affiliation(s)
- Francisco Correia
- Department of Oral Surgery and Periodontology, Faculty of Dental Medicine, University of Porto, Porto, Portugal
| | - Daniel Humberto Pozza
- Departamento de Biomedicina da Faculdade de Medicina, and Faculdade de Ciências da Nutrição e Alimentação, and I3s, Universidade do Porto, Porto, Portugal and Universidad Europea de Madrid
| | - Sónia Gouveia
- Instituto de Engenharia Eletrónica e Informática de Aveiro (IEETA/UA) and Centro de I&D em Matemática e Aplicações (CIDMA/UA), Universidade de Aveiro (UA), Portugal
| | - António Felino
- Department of Oral Surgery and Periodontology, Faculty of Dental Medicine, University of Porto, Porto, Portugal
| | - Ricardo Faria E Almeida
- Department of Oral Surgery and Periodontology, Faculty of Dental Medicine, University of Porto, Porto, Portugal
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13
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Confalonieri D, Schwab A, Walles H, Ehlicke F. Advanced Therapy Medicinal Products: A Guide for Bone Marrow-derived MSC Application in Bone and Cartilage Tissue Engineering. TISSUE ENGINEERING PART B-REVIEWS 2017; 24:155-169. [PMID: 28990462 DOI: 10.1089/ten.teb.2017.0305] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Millions of people worldwide suffer from trauma- or age-related orthopedic diseases such as osteoarthritis, osteoporosis, or cancer. Tissue Engineering (TE) and Regenerative Medicine are multidisciplinary fields focusing on the development of artificial organs, biomimetic engineered tissues, and cells to restore or maintain tissue and organ function. While allogenic and future autologous transplantations are nowadays the gold standards for both cartilage and bone defect repair, they are both subject to important limitations such as availability of healthy tissue, donor site morbidity, and graft rejection. Tissue engineered bone and cartilage products represent a promising and alternative approach with the potential to overcome these limitations. Since the development of Advanced Therapy Medicinal Products (ATMPs) such as TE products requires the knowledge of diverse regulation and an extensive communication with the national/international authorities, the aim of this review is therefore to summarize the state of the art on the clinical applications of human bone marrow-derived stromal cells for cartilage and bone TE. In addition, this review provides an overview of the European legislation to facilitate the development and commercialization of new ATMPs.
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Affiliation(s)
- Davide Confalonieri
- 1 Department Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg , Wuerzburg, Germany
| | - Andrea Schwab
- 1 Department Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg , Wuerzburg, Germany
| | - Heike Walles
- 1 Department Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg , Wuerzburg, Germany .,2 Translational Center Wuerzburg "Regenerative Therapies in Oncology and Musculoskeletal Disease," Wuerzburg, Germany
| | - Franziska Ehlicke
- 1 Department Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg , Wuerzburg, Germany
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14
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Yasui T, Mabuchi Y, Morikawa S, Onizawa K, Akazawa C, Nakagawa T, Okano H, Matsuzaki Y. Isolation of dental pulp stem cells with high osteogenic potential. Inflamm Regen 2017; 37:8. [PMID: 29259707 PMCID: PMC5725894 DOI: 10.1186/s41232-017-0039-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Accepted: 02/23/2017] [Indexed: 01/05/2023] Open
Abstract
Dental pulp stem cells/progenitor cells (DPSCs) can be easily obtained and can have excellent proliferative and mineralization potentials. Therefore, many studies have investigated the isolation and bone formation of DPSCs. In most previous reports, human DPSCs were traditionally isolated by exploiting their ability to adhere to plastic tissue culture dishes. DPSCs isolated by plastic adherence are frequently contaminated by other cells, which limits the ability to investigate their basic biology and regenerative properties. Additionally, the proliferative and osteogenic potentials vary depending on the isolated cells. It is very difficult to obtain cells of a sufficient quality to elicit the required effect upon transplantation. Considering clinical applications, stem cells used for regenerative medicine need to be purified in order to increase the efficiency of bone regeneration, and a stable supply of these cells must be generated. Here, we review the purification of DPSCs and studies of cranio-maxillofacial bone regeneration using these cells. Additionally, we introduce the prospective isolation of DPSCs using specific cell surface markers: low-affinity nerve growth factor and thymocyte antigen 1.
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Affiliation(s)
- Takazumi Yasui
- Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan.,Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan.,Department of Dentistry and Oral Surgery, Kawasaki Municipal Kawasaki Hospital, 12-1 Shinkawadori, Kawasaki-ku, Kawasaki, Kanagawa 210-0013 Japan
| | - Yo Mabuchi
- Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan.,Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510 Japan
| | - Satoru Morikawa
- Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
| | - Katsuhiro Onizawa
- Department of Dentistry and Oral Surgery, Kawasaki Municipal Kawasaki Hospital, 12-1 Shinkawadori, Kawasaki-ku, Kawasaki, Kanagawa 210-0013 Japan
| | - Chihiro Akazawa
- Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510 Japan
| | - Taneaki Nakagawa
- Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
| | - Hideyuki Okano
- Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan
| | - Yumi Matsuzaki
- Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582 Japan.,Department of Cancer Biology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501 Japan
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15
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Fernandes G, Yang S. Application of platelet-rich plasma with stem cells in bone and periodontal tissue engineering. Bone Res 2016; 4:16036. [PMID: 28018706 PMCID: PMC5153571 DOI: 10.1038/boneres.2016.36] [Citation(s) in RCA: 106] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Revised: 08/19/2016] [Accepted: 08/23/2016] [Indexed: 12/17/2022] Open
Abstract
Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone loss. Autogenous bone is the present gold standard of bone regeneration. However, disadvantages like donor site morbidity and its decreased availability limit its use. Even allografts and synthetic grafting materials have their own limitations. As certain specific stem cells can be directed to differentiate into an osteoblastic lineage in the presence of growth factors (GFs), it makes stem cells the ideal agents for bone regeneration. Furthermore, platelet-rich plasma (PRP), which can be easily isolated from whole blood, is often used for bone regeneration, wound healing and bone defect repair. When stem cells are combined with PRP in the presence of GFs, they are able to promote osteogenesis. This review provides in-depth knowledge regarding the use of stem cells and PRP in vitro, in vivo and their application in clinical studies in the future.
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Affiliation(s)
- Gabriela Fernandes
- Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY, USA
| | - Shuying Yang
- Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY, USA
- Developmental Genomics Group, New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA
- Department of Anatomy & Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
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16
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Saeed H, Ahsan M, Saleem Z, Iqtedar M, Islam M, Danish Z, Khan AM. Mesenchymal stem cells (MSCs) as skeletal therapeutics - an update. J Biomed Sci 2016; 23:41. [PMID: 27084089 PMCID: PMC4833928 DOI: 10.1186/s12929-016-0254-3] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2016] [Accepted: 04/03/2016] [Indexed: 12/13/2022] Open
Abstract
Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair/regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/serum or by loading onto repair/induction supportive resorb-able scaffolds. Thus, this review is aimed at highlighting a wide range of pertinent clinical therapeutic options of MSCs in the treatment of skeletal diseases and skeletal tissue regeneration. Additionally, in skeletal disease and regenerative sections, only the early and more recent preclinical evidences are discussed followed by all the pertinent clinical studies. Moreover, germane post transplant therapeutic mechanisms afforded by MSCs have also been conversed. Nonetheless, assertive use of MSCs in the clinic for skeletal disorders and repair is far from a mature therapeutic option, therefore, posed challenges and future directions are also discussed. Importantly, for uniformity at all instances, term MSCs is used throughout the review.
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Affiliation(s)
- Hamid Saeed
- Section of Clinical Pharmacy, University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, 54000, Lahore, Pakistan.
| | - Muhammad Ahsan
- Section of Clinical Pharmacy, University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, 54000, Lahore, Pakistan
| | - Zikria Saleem
- Section of Clinical Pharmacy, University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, 54000, Lahore, Pakistan
| | - Mehwish Iqtedar
- Department of Bio-technology, Lahore College for Women University, Lahore, Pakistan
| | - Muhammad Islam
- Section of Clinical Pharmacy, University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, 54000, Lahore, Pakistan
| | - Zeeshan Danish
- Section of Clinical Pharmacy, University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, 54000, Lahore, Pakistan
| | - Asif Manzoor Khan
- Department of Biochemistry and Molecular Biology, University of the Southern Denmark, 5230, Odense, Denmark
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17
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Lemos CAA, Mello CC, dos Santos DM, Verri FR, Goiato MC, Pellizzer EP. Effects of platelet-rich plasma in association with bone grafts in maxillary sinus augmentation: a systematic review and meta-analysis. Int J Oral Maxillofac Surg 2016; 45:517-25. [PMID: 26775635 DOI: 10.1016/j.ijom.2015.07.012] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Revised: 07/06/2015] [Accepted: 07/15/2015] [Indexed: 01/13/2023]
Abstract
This systematic review evaluated the effect on bone formation and implant survival of combining platelet-rich plasma (PRP) with bone grafts in maxillary augmentation. A comprehensive review of articles listed in the PubMed/MEDLINE, Embase, and Cochrane Library databases covering the period January 2000 to January 2015 was performed. The meta-analysis was based on bone formation for which the mean difference (MD, in millimetres) was calculated. Implant survival was assessed as a dichotomous outcome and evaluated using the risk ratio (RR) with 95% confidence interval (CI). The search identified 3303 references. After inclusion and exclusion criteria were applied, 17 studies were selected for qualitative analysis and 13 for quantitative analysis. A total of 369 patients (mean age 51.67 years) and 621 maxillary sinus augmentations were evaluated. After the data analysis, additional analyses were performed of the implant stability quotient, marginal bone loss, and alveolar bone height measured by MD. The results showed no significant difference in implant stability (P=0.32, MD 1.00, 95% CI -0.98 to 2.98), marginal bone loss (P=0.31, MD 0.06, 95% CI -0.05 to 0.16), alveolar bone height (P=0.10, MD -0.72, 95% CI -1.59 to 0.14), implant survival (P=0.22, RR 1.95, 95% CI 0.67-5.69), or bone formation (P=0.81, MD -0.63, 95% CI -5.91 to 4.65). In conclusion, the meta-analysis indicates no influence of PRP with bone graft on bone formation and implant survival in maxillary sinus augmentation.
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Affiliation(s)
- C A A Lemos
- Department of Dental Materials and Prosthodontics, Araçatuba Dental School, UNESP - Universidade Estadual Paulista, Araçatuba, Brazil
| | - C C Mello
- Department of Dental Materials and Prosthodontics, Araçatuba Dental School, UNESP - Universidade Estadual Paulista, Araçatuba, Brazil
| | - D M dos Santos
- Department of Dental Materials and Prosthodontics, Araçatuba Dental School, UNESP - Universidade Estadual Paulista, Araçatuba, Brazil
| | - F R Verri
- Department of Dental Materials and Prosthodontics, Araçatuba Dental School, UNESP - Universidade Estadual Paulista, Araçatuba, Brazil
| | - M C Goiato
- Department of Dental Materials and Prosthodontics, Araçatuba Dental School, UNESP - Universidade Estadual Paulista, Araçatuba, Brazil
| | - E P Pellizzer
- Department of Dental Materials and Prosthodontics, Araçatuba Dental School, UNESP - Universidade Estadual Paulista, Araçatuba, Brazil.
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18
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Hibi H. Clinical review of bone regenerative medicine and maxillomandibular reconstruction. ACTA ACUST UNITED AC 2016. [DOI: 10.1016/s1348-8643(15)00037-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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19
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Bone Marrow Stromal Stem Cells for Bone Repair: Basic and Translational Aspects. RECENT ADVANCES IN STEM CELLS 2016. [DOI: 10.1007/978-3-319-33270-3_10] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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20
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Erdogan Ö, Supachawaroj N, Soontornvipart K, Kheolamai P. Treatment of Peri-Implant Defects in the Rabbit's Tibia with Adipose or Bone Marrow-Derived Mesenchymal Stems Cells. Clin Implant Dent Relat Res 2015; 18:1003-1014. [PMID: 26402880 DOI: 10.1111/cid.12378] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Mesenchymal stem cell (MSC) treatment in conjunction with bone graft materials or space filler can be an alternative to autogenous bone grafts in the treatment of peri-implant bone defects. PURPOSE To evaluate the success of bone regeneration capacity of adipose-derived and bone marrow-derived MSCs for the treatment of peri-implant bone defects when applied with a beta-tricalcium phosphate/collagen-based scaffold. MATERIAL AND METHODS Forty implants were placed into the tibiae of 10 rabbits bilaterally. Surgical defects created around the implants were treated with one the following treatment modalities: 1) adipose-derived MSC transplanted scaffold + collagen membrane; 2) bone marrow-derived MSC transplanted scaffold + collagen membrane; 3) autogenous bone + collagen membrane; and 4) collagen membrane only. The bone regeneration capacity of each technique was determined by histomorphometry, micro-CT, and measuring the implant stability by resonance frequency analysis. RESULTS One limb of one rabbit was excluded because of fracture, and another limb was excluded because of infection. All parameters on 36 implants revealed that both sources of MSC can form equivalently new bone that is comparable with autogenous bone. The defects treated with membrane only had significantly less bone formation compared with other groups. CONCLUSION Both adipose-derived and bone marrow-derived MSC treatments are feasible alternatives to autogenous bone grafts in the treatment of peri-implant osseos defects.
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Affiliation(s)
- Özgür Erdogan
- Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Rangsit University, Bangkok, Thailand.
| | - Nuttawut Supachawaroj
- Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Rangsit University, Bangkok, Thailand
| | - Kumpanart Soontornvipart
- Department of Surgery, Faculty of Veterinary Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pakpoom Kheolamai
- Center of Excellence in Stem Cell Research, Faculty of Medicine, Thammasat University, Pathumtani, Thailand
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21
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Mangano FG, Colombo M, Veronesi G, Caprioglio A, Mangano C. Mesenchymal stem cells in maxillary sinus augmentation: A systematic review with meta-analysis. World J Stem Cells 2015; 7:976-991. [PMID: 26240683 PMCID: PMC4515439 DOI: 10.4252/wjsc.v7.i6.976] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Revised: 03/27/2015] [Accepted: 05/06/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effectiveness of mesenchymal stem cells (MSCs) in maxillary sinus augmentation (MSA), with various scaffold materials.
METHODS: MEDLINE, EMBASE and SCOPUS were searched using keywords such as sinus graft, MSA, maxillary sinus lift, sinus floor elevation, MSC and cell-based, in different combinations. The searches included full text articles written in English, published over a 10-year period (2004-2014). Inclusion criteria were clinical/radiographic and histologic/ histomorphometric studies in humans and animals, on the use of MSCs in MSA. Meta-analysis was performed only for experimental studies (randomized controlled trials and controlled trials) involving MSA, with an outcome measurement of histologic evaluation with histomorphometric analysis reported. Mean and standard deviation values of newly formed bone from each study were used, and weighted mean values were assessed to account for the difference in the number of subjects among the different studies. To compare the results between the test and the control groups, the differences of regenerated bone in mean and 95% confidence intervals were calculated.
RESULTS: Thirty-nine studies (18 animal studies and 21 human studies) published over a 10-year period (between 2004 and 2014) were considered to be eligible for inclusion in the present literature review. These studies demonstrated considerable variation with respect to study type, study design, follow-up, and results. Meta-analysis was performed on 9 studies (7 animal studies and 2 human studies). The weighted mean difference estimate from a random-effect model was 9.5% (95%CI: 3.6%-15.4%), suggesting a positive effect of stem cells on bone regeneration. Heterogeneity was measured by the I2 index. The formal test confirmed the presence of substantial heterogeneity (I2 = 83%, P < 0.0001). In attempt to explain the substantial heterogeneity observed, we considered a meta-regression model with publication year, support type (animal vs humans) and follow-up length (8 or 12 wk) as covariates. After adding publication year, support type and follow-up length to the meta-regression model, heterogeneity was no longer significant (I2 = 33%, P = 0.25).
CONCLUSION: Several studies have demonstrated the potential for cell-based approaches in MSA; further clinical trials are needed to confirm these results.
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Clinical Application of Mesenchymal Stem Cells and Novel Supportive Therapies for Oral Bone Regeneration. BIOMED RESEARCH INTERNATIONAL 2015; 2015:341327. [PMID: 26064899 PMCID: PMC4443638 DOI: 10.1155/2015/341327] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Revised: 04/07/2015] [Accepted: 04/14/2015] [Indexed: 02/06/2023]
Abstract
Bone regeneration is often needed prior to dental implant treatment due to the lack of adequate quantity and quality of the bone after infectious diseases, trauma, tumor, or congenital conditions. In these situations, cell transplantation technologies may help to overcome the limitations of autografts, xenografts, allografts, and alloplastic materials. A database search was conducted to include human clinical trials (randomized or controlled) and case reports/series describing the clinical use of mesenchymal stem cells (MSCs) in the oral cavity for bone regeneration only specifically excluding periodontal regeneration. Additionally, novel advances in related technologies are also described. 190 records were identified. 51 articles were selected for full-text assessment, and only 28 met the inclusion criteria: 9 case series, 10 case reports, and 9 randomized controlled clinical trials. Collectively, they evaluate the use of MSCs in a total of 290 patients in 342 interventions. The current published literature is very diverse in methodology and measurement of outcomes. Moreover, the clinical significance is limited. Therefore, the use of these techniques should be further studied in more challenging clinical scenarios with well-designed and standardized RCTs, potentially in combination with new scaffolding techniques and bioactive molecules to improve the final outcomes.
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23
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In vitro induction of alkaline phosphatase levels predicts in vivo bone forming capacity of human bone marrow stromal cells. Stem Cell Res 2014; 12:428-40. [DOI: 10.1016/j.scr.2013.12.001] [Citation(s) in RCA: 104] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2012] [Revised: 11/29/2013] [Accepted: 12/03/2013] [Indexed: 12/25/2022] Open
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25
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Schliephake H. Clinical Efficacy of Growth Factors to Enhance Tissue Repair in Oral and Maxillofacial Reconstruction: A Systematic Review. Clin Implant Dent Relat Res 2013; 17:247-73. [DOI: 10.1111/cid.12114] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Henning Schliephake
- Abteilung für Mund-, Kiefer-und Gesichtschirurgie; Georg-August-Universität; Göttingen Germany
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26
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Jakobsen C, Sørensen JA, Kassem M, Thygesen TH. Mesenchymal stem cells in oral reconstructive surgery: a systematic review of the literature. J Oral Rehabil 2013; 40:693-706. [DOI: 10.1111/joor.12079] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2013] [Indexed: 11/30/2022]
Affiliation(s)
- C. Jakobsen
- Department of Oral and Maxillofacial Surgery; Odense University Hospital (OUH); Odense Denmark
| | - J. A. Sørensen
- Department of Plastic and Reconstructive Surgery; Odense University Hospital (OUH); Odense Denmark
| | - M. Kassem
- Endocrinology Research Unit; Odense University Hospital (OUH); Odense Denmark
| | - T. H. Thygesen
- Department of Oral and Maxillofacial Surgery; Odense University Hospital (OUH); Odense Denmark
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Shanbhag S, Shanbhag V. Clinical applications of cell-based approaches in alveolar bone augmentation: a systematic review. Clin Implant Dent Relat Res 2013; 17 Suppl 1:e17-34. [PMID: 23815469 DOI: 10.1111/cid.12103] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Cell-based approaches, utilizing adult mesenchymal stem cells (MSCs), are reported to overcome the limitations of conventional bone augmentation procedures. PURPOSE The study aims to systematically review the available evidence on the characteristics and clinical effectiveness of cell-based ridge augmentation, socket preservation, and sinus-floor augmentation, compared to current evidence-based methods in human adult patients. MATERIALS AND METHODS MEDLINE, EMBASE, and CENTRAL databases were searched for related literature. Both observational and experimental studies reporting outcomes of "tissue engineered" or "cell-based" augmentation in ≥5 adult patients alone, or in comparison with non-cell-based (conventional) augmentation methods, were eligible for inclusion. Primary outcome was histomorphometric analysis of new bone formation. Effectiveness of cell-based augmentation was evaluated based on outcomes of controlled studies. RESULTS Twenty-seven eligible studies were identified. Of these, 15 included a control group (8 randomized controlled trials [RCTs]), and were judged to be at a moderate-to-high risk of bias. Most studies reported the combined use of cultured autologous MSCs with an osteoconductive bone substitute (BS) scaffold. Iliac bone marrow and mandibular periosteum were frequently reported sources of MSCs. In vitro culture of MSCs took between 12 days and 1.5 months. A range of autogenous, allogeneic, xenogeneic, and alloplastic scaffolds was identified. Bovine bone mineral scaffold was frequently reported with favorable outcomes, while polylactic-polyglycolic acid copolymer (PLGA) scaffold resulted in graft failure in three studies. The combination of MSCs and BS resulted in outcomes similar to autogenous bone (AB) and BS. Three RCTs and one controlled trial reported significantly greater bone formation in cell-based than conventionally grafted sites after 3 to 8 months. CONCLUSIONS Based on limited controlled evidence at a moderate-to-high risk of bias, cell-based approaches are comparable, if not superior, to current evidence-based bone grafting methods, with a significant advantage of avoiding AB harvesting. Future clinical trials should additionally evaluate patient-based outcomes and the time-/cost-effectiveness of these approaches.
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28
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Reconstruction of Human Mandibular Continuity Defects With Allogenic Scaffold and Autologous Marrow Mesenchymal Stem Cells. J Craniofac Surg 2013; 24:1292-7. [DOI: 10.1097/scs.0b013e318294288a] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
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29
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Khojasteh A, Morad G, Behnia H. Clinical Importance of Recipient Site Characteristics for Vertical Ridge Augmentation: A Systematic Review of Literature and Proposal of a Classification. J ORAL IMPLANTOL 2013; 39:386-98. [DOI: 10.1563/aaid-joi-d-11-00210] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
This review evaluated the characteristics of vertical alveolar defects that were augmented via onlay bone grafting or guided bone regeneration. Information regarding the anatomic site, type of edentulism, and defects' dimensions were extracted. The experiments differed vastly in the description of the defects' features. Aiming to mitigate the confounding effect of recipient site's morphology in future experiments, a classification of vertically deficient recipient sites is proposed.
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Affiliation(s)
- Arash Khojasteh
- 1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Dental Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Golnaz Morad
- 2 Dental Research Center, Faculty of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Behnia
- 1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Dental Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Boeckel DG, Shinkai RSA, Grossi ML, Teixeira ER. Cell culture-based tissue engineering as an alternative to bone grafts in implant dentistry: a literature review. J ORAL IMPLANTOL 2013; 38 Spec No:538-45. [PMID: 23072286 DOI: 10.1563/aaid-joi-d-11-00197] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Several biomaterials and techniques for bone grafting have been described in the literature for atresic bone tissue replacement caused by edentulism, surgical resectioning, and traumas. A new technique involves tissue engineering, a promising option to replace bone tissue and solve problems associated with morbidity of autogenous grafting. This literature review aims to describe tissue-engineering techniques using ex vivo cell culture as an alternative to repair bone maxillary atresias and discuss the concepts and potentials of bone regeneration through cell culture techniques as an option for restorative maxillofacial surgery.
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Boeckel DG, Shinkai RSA, Grossi ML, Teixeira ER. In vitro evaluation of cytotoxicity of hyaluronic acid as an extracellular matrix on OFCOL II cells by the MTT assay. Oral Surg Oral Med Oral Pathol Oral Radiol 2012; 117:e423-8. [PMID: 23146572 DOI: 10.1016/j.oooo.2012.07.486] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Revised: 05/17/2012] [Accepted: 07/20/2012] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To evaluate the cytotoxicity of hyaluronic acid (HA) on a tissue-engineered compound for bone grafting containing osteoblastic cells (OFCOL II), platelet-rich plasma (PRP) with or without thrombin (Thr), and hydroxyapatite (HP) by the MTT assay. STUDY DESIGN Studied groups were formed as follows: (A) Cells + HA + PRP with Thr + hydroxyapatite (HP); (B) Cells + HA + PRP + HP; (C) Cells + HA + HP; (D) Cells + HP; (E) Cells + HA; (F) Cells + PRP with Thr; (G) Cells + PRP; and (H) Pure Dulbecco's modified Eagle's medium (DMEM) with 15% fetal bovine serum. A 2-way ANOVA and Tukey's test were applied for statistical analysis (P < .05). RESULTS Results of cell viability for each group were as follows: A: 79%, B: 67%, C: 68%, D: 99%, E: 74%, G: 89%, F: 90%, and Group H: 100%. CONCLUSIONS Results suggested a decrease in cell viability in the presence of HA.
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Affiliation(s)
| | - Rosemary Sadami Arai Shinkai
- Associate Professor, Graduate Program in Dentistry, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Márcio Lima Grossi
- Associate Professor, Graduate Program in Dentistry, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Eduardo Rolim Teixeira
- Professor, Graduate Program in Dentistry, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
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Stem cells in dentistry--Part II: Clinical applications. J Prosthodont Res 2012; 56:229-48. [PMID: 23137671 DOI: 10.1016/j.jpor.2012.10.001] [Citation(s) in RCA: 114] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2012] [Accepted: 10/03/2012] [Indexed: 12/29/2022]
Abstract
New technologies that facilitate solid alveolar ridge augmentation are receiving considerable attention in the field of prosthodontics because of the growing requirement for esthetic and functional reconstruction by dental implant treatments. Recently, several studies have demonstrated potential advantages for stem-cell-based therapies in regenerative treatments. Mesenchymal stem/stromal cells (MSCs) are now an excellent candidate for tissue replacement therapies, and tissue engineering approaches and chair-side cellular grafting approaches using autologous MSCs represent the clinical state of the art for stem-cell-based alveolar bone regeneration. Basic studies have revealed that crosstalk between implanted donor cells and recipient immune cells plays a key role in determining clinical success that may involve the recently observed immunomodulatory properties of MSCs. Part II of this review first overviews progress in regenerative dentistry to consider the implications of the stem cell technology in dentistry and then highlights cutting-edge stem-cell-based alveolar bone regenerative therapies. Factors that affect stem-cell-based bone regeneration as related to the local immune response are then discussed. Additionally, pre-clinical stem cell studies for the regeneration of teeth and other oral organs as well as possible applications of MSC-based immunotherapy in dentistry are outlined. Finally, the marketing of stem cell technology in dental stem cell banks with a view toward future regenerative therapies is introduced.
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Egusa H, Sonoyama W, Nishimura M, Atsuta I, Akiyama K. Stem cells in dentistry--part I: stem cell sources. J Prosthodont Res 2012; 56:151-65. [PMID: 22796367 DOI: 10.1016/j.jpor.2012.06.001] [Citation(s) in RCA: 223] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2012] [Accepted: 06/14/2012] [Indexed: 12/21/2022]
Abstract
Stem cells can self-renew and produce different cell types, thus providing new strategies to regenerate missing tissues and treat diseases. In the field of dentistry, adult mesenchymal stem/stromal cells (MSCs) have been identified in several oral and maxillofacial tissues, which suggests that the oral tissues are a rich source of stem cells, and oral stem and mucosal cells are expected to provide an ideal source for genetically reprogrammed cells such as induced pluripotent stem (iPS) cells. Furthermore, oral tissues are expected to be not only a source but also a therapeutic target for stem cells, as stem cell and tissue engineering therapies in dentistry continue to attract increasing clinical interest. Part I of this review outlines various types of intra- and extra-oral tissue-derived stem cells with regard to clinical availability and applications in dentistry. Additionally, appropriate sources of stem cells for regenerative dentistry are discussed with regard to differentiation capacity, accessibility and possible immunomodulatory properties.
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Affiliation(s)
- Hiroshi Egusa
- Department of Fixed Prosthodontics, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
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Nagata M, Hoshina H, Li M, Arasawa M, Uematsu K, Ogawa S, Yamada K, Kawase T, Suzuki K, Ogose A, Fuse I, Okuda K, Uoshima K, Nakata K, Yoshie H, Takagi R. A clinical study of alveolar bone tissue engineering with cultured autogenous periosteal cells: coordinated activation of bone formation and resorption. Bone 2012; 50:1123-9. [PMID: 22406494 DOI: 10.1016/j.bone.2012.02.631] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Revised: 02/16/2012] [Accepted: 02/23/2012] [Indexed: 11/18/2022]
Abstract
In ongoing clinical research into the use of cultured autogenous periosteal cells (CAPCs) in alveolar bone regeneration, CAPCs were grafted into 33 sites (15 for alveolar ridge augmentation and 18 for maxillary sinus lift) in 25 cases. CAPCs were cultured for 6weeks, mixed with particulate autogenous bone and platelet-rich plasma, and then grafted into the sites. Clinical outcomes were determined from high-resolution three-dimensional computed tomography (3D-CT) images and histological findings. No serious adverse events were attributable to the use of grafted CAPCs. Bone regeneration was satisfactory even in cases of advanced atrophy of the alveolar process. Bone biopsy after bone grafting with CAPCs revealed prominent recruitment of osteoblasts and osteoclasts accompanied by angiogenesis around the regenerated bone. 3D-CT imaging suggested that remodeling of the grafted autogenous cortical bone particles was faster in bone grafting with CAPCs than in conventional bone grafting. The use of CAPCs offers cell-based bone regeneration therapy, affording complex bone regeneration across a wide area, and thus expanding the indications for dental implants. Also, it enables the content of particulate autogenous bone in the graft material to be reduced to as low as 40%, making the procedure less invasive, or enabling larger amounts of graft materials to be prepared. It may also be possible to dispense with the use of autogenous bone altogether in the future. The results suggest that CAPC grafting induces bone remodeling, thereby enhancing osseointegration and consequently reducing postoperative waiting time after dental implant placement.
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Affiliation(s)
- Masaki Nagata
- Department of Oral and Maxillofacial Surgery, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
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Neman J, Hambrecht A, Cadry C, Jandial R. Stem cell-mediated osteogenesis: therapeutic potential for bone tissue engineering. Biologics 2012; 6:47-57. [PMID: 22500114 PMCID: PMC3324839 DOI: 10.2147/btt.s22407] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Intervertebral disc degeneration often requires bony spinal fusion for long-term relief. Current arthrodesis procedures use bone grafts from autogenous bone, allogenic backed bone, or synthetic materials. Autogenous bone grafts can result in donor site morbidity and pain at the donor site, while allogenic backed bone and synthetic materials have variable effectiveness. Given these limitations, researchers have focused on new treatments that will allow for safe and successful bone repair and regeneration. Mesenchymal stem cells have received attention for their ability to differentiate into osteoblasts, cells that synthesize new bone. With the recent advances in scaffold and biomaterial technology as well as stem cell manipulation and transplantation, stem cells and their scaffolds are uniquely positioned to bring about significant improvements in the treatment and outcomes of spinal fusion and other injuries.
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Affiliation(s)
- Josh Neman
- Department of Neurosurgery, Beckman Research Institute, City of Hope National Cancer Center, Duarte
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Zhang ZY, Teoh SH, Hui JHP, Fisk NM, Choolani M, Chan JKY. The potential of human fetal mesenchymal stem cells for off-the-shelf bone tissue engineering application. Biomaterials 2012; 33:2656-72. [PMID: 22217806 DOI: 10.1016/j.biomaterials.2011.12.025] [Citation(s) in RCA: 108] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2011] [Accepted: 12/13/2011] [Indexed: 12/13/2022]
Abstract
Mesenchymal stem cells (MSCs) have become one of the most promising cell sources for bone tissue engineering (BTE) applications. In this review, we first highlight recent progress in the understanding of MSC biology, their in vivo niche, multi-faceted contribution to fracture healing and bone re-modelling, and their role in BTE. A literature review from clinicaltrials.gov and Pubmed on clinical usage of MSC for both orthopedic and non-orthopedic indications suggests that translational use of MSC for BTE indications is likely to bear fruit in the ensuing decade. Last, we disscuss the profound influence of ontological and antomical origins of MSC on their proliferation and osteogenesis and demonstrated human fetal MSC (hfMSC) as a superior cellular candidate for off-the-shelf BTE applications. This relates to their superior proliferation capacity, more robust osteogenic potential and lower immunogenecity, as compared to MSC from perinatal and postnatal sources. Furthermore, we discuss our experience in developing a hfMSC based BTE strategy with the integrated use of bioreactor-based dynamic priming within macroporous scaffolds, now ready for evaluation in clinical trials. In conclusion, hfMSC is likely the most promising cell source for allogeneic based BTE application, with proven advantages compared to other MSC based ones.
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Affiliation(s)
- Zhi-Yong Zhang
- Mechanical Engineering, Faculty of Engineering, National University of Singapore, Singapore
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Neman J, Hambrecht A, Cadry C, Goodarzi A, Youssefzadeh J, Chen MY, Jandial R. Clinical Efficacy of Stem Cell Mediated Osteogenesis and Bioceramics for Bone Tissue Engineering. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2012; 760:174-87. [DOI: 10.1007/978-1-4614-4090-1_11] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region. Front Med 2011; 5:401-13. [PMID: 22198752 DOI: 10.1007/s11684-011-0161-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2011] [Accepted: 09/27/2011] [Indexed: 12/15/2022]
Abstract
Clinical imperatives for the reconstruction of jaw bone defects or resorbed alveolar ridge require new therapies or procedures instead of autologous/allogeneic bone grafts. Regenerative medicine, based on stem cell science and tissue engineering technology, is considered as an ideal alternative strategy for bone regeneration. In this paper, we review the current choices of cell source and strategies on directing the osteogenic differentiation of stem cells. The preclinical animal models for bone regeneration and the key translational points to clinical success in oral and maxillofacial region are also discussed. We propose comprehensive strategies based on stem cell and tissue engineering researches, allowing for clinical application in oral and maxillofacial region.
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An experimental study of bone healing around the titanium screw implants in ovariectomized rats: enhancement of bone healing by bone marrow stromal cells transplantation. IMPLANT DENT 2011; 20:236-45. [PMID: 21613950 DOI: 10.1097/id.0b013e3182199543] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE : This study is to evaluate the bone quality of surrounding areas of implants with bone marrow stromal cells (BMSCs) transplantation to rat femur, which have become osteoporosis-induced models. MATERIALS AND METHODS : The Sprague-Dawley rats were divided into 3 groups: the first group where their ovaries were removed (OVX group), the second group where a sham surgery was given (SHAM group), and the third group where BMSCs were transplanted to an OVX group (OVX-BMSCs group). In the OVX-BMSCs group, 1 × 10 BMSCs were transplanted into femur with implant. Each value of the bone to implant contact and the bone area of each cortical bone and cancellous bone was obtained. Bone density of the width of 500 μm from the implants was measured. RESULTS : Each ratio of bone to implant contact, bone area, and bone density in the OVX-BMSCs group was significantly higher than those of OVX group as to the cancellous bone. CONCLUSION : The BMSCs transplantation therapy improved local bone healing in the cancellous bone surrounding implants and also significantly improved bone binding with implants.
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Khojasteh A, Behnia H, Dashti SG, Stevens M. Current trends in mesenchymal stem cell application in bone augmentation: a review of the literature. J Oral Maxillofac Surg 2011; 70:972-82. [PMID: 21763048 DOI: 10.1016/j.joms.2011.02.133] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2010] [Revised: 02/14/2011] [Accepted: 02/21/2011] [Indexed: 01/10/2023]
Abstract
PURPOSE The literature regarding mesenchymal stem cell (MSC)-based bone reconstruction techniques are sparse and no comprehensive review of current methods has been performed. The aim of this article was to provide a discussion of clinical and experimental reports of MSC application in the reconstruction of bony defects in live models. MATERIALS AND METHODS This search was executed using the PubMed database with various combinations of related keywords. Currently published English-language studies that had applied MSCs as a part of their treatment protocol for reconstruction of bony defects in rat, rabbit, dog, and human models were reviewed. The included studies had reported substantiation that the applied cells were of MSC origin as a part of the study design. Publications inclusive to February 1, 2010 were evaluated. Of review of 187 found abstracts and full texts, 25 articles met the inclusion criteria. RESULT Based on this review, tremendous differences exist among investigators for the application of MSCs in bone augmentation procedures. These differences include not only species uniqueness but also a plethora of other variances, such as stem cell source, defect sites and sizes, carriers and constructs, use of additional growth factors, measured parameters, and methods of data collection. CONCLUSION Because of the multitude of protocols, range of parameters, and data in the current English-language literature, this review did not reach any significant conclusion as to the "most predictable" model in stem cell reconstruction. However, it does "shed light" on the need for additional collaborated studies using similar homogenous designs and data analysis in advancing the science of bone reconstruction using MSCs.
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Affiliation(s)
- Arash Khojasteh
- Division of Basic Sciences, Dental Research Center, Department of Oral and Maxillofacial Surgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Sauerbier S, Rickert D, Gutwald R, Nagursky H, Oshima T, Xavier SP, Christmann J, Kurz P, Menne D, Vissink A, Raghoebar G, Schmelzeisen R, Wagner W, Koch FP. Bone marrow concentrate and bovine bone mineral for sinus floor augmentation: a controlled, randomized, single-blinded clinical and histological trial--per-protocol analysis. Tissue Eng Part A 2011; 17:2187-97. [PMID: 21529247 DOI: 10.1089/ten.tea.2010.0516] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
PURPOSE The purpose of this work was to evaluate the potential of substituting autogenous bone (AB) by bone marrow aspirate concentrate (BMAC). Both AB and BMAC were tested in combination with a bovine bone mineral (BBM) for their ability of new bone formation (NBF) in a multicentric, randomized, controlled, clinical and histological noninferiority trial. MATERIALS AND METHODS Forty-five severely atrophied maxillary sinus from 26 patients were evaluated in a partial cross-over design. As test arm, 34 sinus of 25 patients were augmented with BBM and BMAC containing mesenchymal stem cells. Eleven control sinus from 11 patients were augmented with a mixture of 70% BBM and 30% AB. Biopsies were obtained after a 3-4-month healing period at time of implant placement and histomorphometrically analyzed for NBF. RESULTS NBF was 14.3%±1.8% for the control and nonsignificantly lower (12.6%±1.7%) for the test (90% confidence interval: -4.6 to 1.2). Values for BBM (31.3%±2.7%) were significantly higher for the test compared with control (19.3%±2.5%) (p<0.0001). Nonmineralized tissue was lower by 3.3% in the test compared with control (57.6%; p=0.137). CONCLUSIONS NBF after 3-4 months is equivalent in sinus, augmented with BMAC and BBM or a mixture of AB and BBM. This technique could be an alternative for using autografts to stimulate bone formation.
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Affiliation(s)
- Sebastian Sauerbier
- Department of Oral and Craniomaxillofacial Surgery, University Hospital Freiburg, Albert-Ludwigs University, Freiburg, Germany.
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Murakami S. Periodontal tissue regeneration by signaling molecule(s): what role does basic fibroblast growth factor (FGF-2) have in periodontal therapy? Periodontol 2000 2011; 56:188-208. [DOI: 10.1111/j.1600-0757.2010.00365.x] [Citation(s) in RCA: 105] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Wang S, Zhang W, Zhao J, Ye D, Zhu C, Yang Y, Zhang X, Sun X, Yang C, Jiang X, Zhang Z. Long-term outcome of cryopreserved bone-derived osteoblasts for bone regeneration in vivo. Biomaterials 2011; 32:4546-55. [PMID: 21459433 DOI: 10.1016/j.biomaterials.2011.03.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2011] [Accepted: 03/07/2011] [Indexed: 01/18/2023]
Abstract
Cryopreserved bone-derived osteoblasts (CBOs) have been considered as a promising cell source for bone regeneration. Previous studies have demonstrated that CBOs had good proliferation and osteogenicity. However, the long-term outcome of CBOs in vivo still remains unknown. In this experiment, we applied CBOs combined with calcium phosphate cement (CPC) to augment maxillary sinus in canine, computer tomography, polychrome labeling, biomechanical tests, fluorescent immunohistochemistry staining and histological analysis were used to analyze the property and mineralization process of the tissue-engineered bone preclinical application. Our results showed that CBOs combined with CPC could promote bone regeneration, dramatically maintain the height, volume and biomechanical property of augmented maxillary sinus. Furthermore, the tissue-engineered bone was more mature than scaffold alone or autogenous bone, and bone formation and remodeling were still apparent 20 months postoperatively. Additionally, 4 months after surgery might be the suitable time point for implants placement in the regenerated bone. These results also indicate that cryopreserved bone may be a potential source of osteoblasts for maxillary sinus augmentation.
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Affiliation(s)
- Shaoyi Wang
- Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
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Sauerbier S, Stubbe K, Maglione M, Haberstroh J, Kuschnierz J, Oshima T, Xavier SP, Brunnberg L, Schmelzeisen R, Gutwald R. Mesenchymal stem cells and bovine bone mineral in sinus lift procedures--an experimental study in sheep. Tissue Eng Part C Methods 2011; 16:1033-9. [PMID: 20050809 DOI: 10.1089/ten.tec.2009.0734] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION New reconstructive and less invasive methods have been searched to optimize bone formation and osseointegration of dental implants in maxillary sinus augmentation. PURPOSE The aim of the presented ovine split-mouth study was to compare bovine bone mineral (BBM) alone and in combination with mesenchymal stem cells (MSCs) regarding their potential in sinus augmentation. MATERIAL AND METHODS Bilateral sinus floor augmentations were performed in six adult sheep. BBM and MSCs were placed into the test side and only BBM in the contra-lateral control side of each sheep. Animals were sacrificed after 8 and 16 weeks. Augmentation sites were analyzed by computed tomography, histology, and histomorphometry. RESULTS The initial volumes of both sides were similar and did not change significantly with time. A tight connection between the particles of BBM and the new bone was observed histologically. Bone formation was significantly (p = 0.027) faster by 49% in the test sides. CONCLUSION The combination of BBM and MSCs accelerated new bone formation in this model of maxillary sinus augmentation. This could allow early placement of implants.
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Affiliation(s)
- Sebastian Sauerbier
- Department of Oral and Maxillofacial Surgery, Albert-Ludwigs-University, Freiburg, Germany.
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Kaigler D, Pagni G, Park CH, Tarle SA, Bartel RL, Giannobile WV. Angiogenic and osteogenic potential of bone repair cells for craniofacial regeneration. Tissue Eng Part A 2010; 16:2809-20. [PMID: 20412009 DOI: 10.1089/ten.tea.2010.0079] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
There has been increased interest in the therapeutic potential of bone marrow derived cells for tissue engineering applications. Bone repair cells (BRCs) represent a unique cell population generated via an ex vivo, closed-system, automated cell expansion process, to drive the propagation of highly osteogenic and angiogenic cells for bone engineering applications. The aims of this study were (1) to evaluate the in vitro osteogenic and angiogenic potential of BRCs, and (2) to evaluate the bone and vascular regenerative potential of BRCs in a craniofacial clinical application. BRCs were produced from bone marrow aspirates and their phenotypes and multipotent potential characterized. Flow cytometry demonstrated that BRCs were enriched for mesenchymal and vascular phenotypes. Alkaline phosphatase and von Kossa staining were performed to assess osteogenic differentiation, and reverse transcriptase-polymerase chain reaction was used to determine the expression levels of bone specific factors. Angiogenic differentiation was determined through in vitro formation of tube-like structures and fluorescent labeling of endothelial cells. Finally, 6 weeks after BRC transplantation into a human jawbone defect, a biopsy of the regenerated site revealed highly vascularized, mineralized bone tissue formation. Taken together, these data provide evidence for the multilineage and clinical potential of BRCs for craniofacial regeneration.
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Affiliation(s)
- Darnell Kaigler
- Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
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Baba S, Inoue T, Hashimoto Y, Kimura D, Ueda M, Sakai K, Matsumoto N, Hiwa C, Adachi T, Hojo M. Effectiveness of scaffolds with pre-seeded mesenchymal stem cells in bone regeneration--assessment of osteogenic ability of scaffolds implanted under the periosteum of the cranial bone of rats. Dent Mater J 2010; 29:673-81. [PMID: 21099156 DOI: 10.4012/dmj.2009-123] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
To date, there has been no study on the development of novel regimens based on the following tissue engineering principles: seeding and culturing mesenchymal stem cells (MSCs) on a scaffold before surgery or injecting cultured MSCs into a scaffold during surgery. The purpose of this study was to assess the in vivo osteogenic ability of scaffold/MSCs implanted beneath the periosteum of the cranial bone of rats in three different sample groups: one in which MSCs were pre-seeded and cultured on a scaffold to produce the 3-D woven fabric scaffold/MSC composite using osteo-lineage induction medium, one in which cultured MSCs produced by osteo-lineage induction in cell cultivation flasks were injected into a scaffold during surgery and a control group, in which only the 3-D woven fabric scaffold was implanted. The results indicate that pre-seeding MSCs on a scaffold leads to a higher osteogenic ability than injecting cultured MSCs into a scaffold during surgery.
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Affiliation(s)
- Shunsuke Baba
- Department of Regenerative Medicine, Foundation for Biomedical Research and Innovation, Kobe, Japan
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Catros S, Guillemot F, Amédée J, Fricain JC. Ingénierie tissulaire osseuse en chirurgie buccale et maxillo-faciale : applications cliniques. ACTA ACUST UNITED AC 2010. [DOI: 10.1051/mbcb/2010031] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Egusa H, Okita K, Kayashima H, Yu G, Fukuyasu S, Saeki M, Matsumoto T, Yamanaka S, Yatani H. Gingival fibroblasts as a promising source of induced pluripotent stem cells. PLoS One 2010; 5:e12743. [PMID: 20856871 PMCID: PMC2939066 DOI: 10.1371/journal.pone.0012743] [Citation(s) in RCA: 125] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2010] [Accepted: 08/23/2010] [Indexed: 01/12/2023] Open
Abstract
Background Induced pluripotent stem (iPS) cells efficiently generated from accessible tissues have the potential for clinical applications. Oral gingiva, which is often resected during general dental treatments and treated as biomedical waste, is an easily obtainable tissue, and cells can be isolated from patients with minimal discomfort. Methodology/Principal Findings We herein demonstrate iPS cell generation from adult wild-type mouse gingival fibroblasts (GFs) via introduction of four factors (Oct3/4, Sox2, Klf4 and c-Myc; GF-iPS-4F cells) or three factors (the same as GF-iPS-4F cells, but without the c-Myc oncogene; GF-iPS-3F cells) without drug selection. iPS cells were also generated from primary human gingival fibroblasts via four-factor transduction. These cells exhibited the morphology and growth properties of embryonic stem (ES) cells and expressed ES cell marker genes, with a decreased CpG methylation ratio in promoter regions of Nanog and Oct3/4. Additionally, teratoma formation assays showed ES cell-like derivation of cells and tissues representative of all three germ layers. In comparison to mouse GF-iPS-4F cells, GF-iPS-3F cells showed consistently more ES cell-like characteristics in terms of DNA methylation status and gene expression, although the reprogramming process was substantially delayed and the overall efficiency was also reduced. When transplanted into blastocysts, GF-iPS-3F cells gave rise to chimeras and contributed to the development of the germline. Notably, the four-factor reprogramming efficiency of mouse GFs was more than 7-fold higher than that of fibroblasts from tail-tips, possibly because of their high proliferative capacity. Conclusions/Significance These results suggest that GFs from the easily obtainable gingival tissues can be readily reprogrammed into iPS cells, thus making them a promising cell source for investigating the basis of cellular reprogramming and pluripotency for future clinical applications. In addition, high-quality iPS cells were generated from mouse GFs without Myc transduction or a specific system for reprogrammed cell selection.
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Affiliation(s)
- Hiroshi Egusa
- Department of Fixed Prosthodontics, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
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Wang P, Qu Y, Man Y. Platelet-rich plasma as a scaffold for injectable soft-tissue augmentation. Cytotherapy 2010; 12:701-2. [DOI: 10.3109/14653249.2010.487901] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Abstract
The dimension of alveolar ridge is decreased by bone atrophy and pneumatization of the maxillary sinus after loss of teeth in the posterior maxilla, and sinus augmentation procedures are performed to create bone quantity and quality to ensure the placement of dental implants.Various osteoconductive materials have been used to augment the sinus floor, but these materials are cell-free and require more time for bone healing. Attempts have been made to apply a cell-based approach that uses mesenchymal stem cells combined with an osteoconductive scaffold. Adult stem cells that can be derived from various tissues including bone marrow, periosteum, and trabecular bone have been applied in sinus augmentation procedures both experimentally and clinically with successful results.In this review, the cell-based approaches in sinus augmentation procedures with various carriers will be described and the efficacy and clinical applicability will be addressed.
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Affiliation(s)
- Jun-Beom Park
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, USA
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