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Abdi SMY, Al-Bakri SSM, Nordin N. Insights on the Characteristics and Therapeutic Potential of Mesenchymal Stem Cell-derived Exosomes for Mitigation of Alzheimer's Disease's Pathogenicity: A Systematic Review. Cell Biochem Biophys 2025; 83:1399-1414. [PMID: 39436580 DOI: 10.1007/s12013-024-01598-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/22/2024] [Indexed: 10/23/2024]
Abstract
Alzheimer's disease (AD) remains a progressive neurodegenerative disease with no cure. Treatment of AD relies on administering drugs that only subside the symptoms. In recent studies, mesenchymal stem cell (MSC)-exosomes have been marked to possess therapeutic potential for treating AD. This study aims to systematically review and analyse findings that focus on the isolation, characterisation, and sources of MSC-derived exosomes used to unravel the therapeutic potential of these exosomes targeting AD using in vitro and in vivo models. It is hypothesised that MSC-exosomes exhibit high therapeutic potential for AD treatment by exerting various modes of action. PubMed, Scopus, and Medline were used to find relevant published works from January 2016 until December 2020, using assigned keywords including "Alzheimer's disease", "secretome", and "exosomes". Only research articles meeting the predefined inclusion/exclusion criteria were selected and analysed. The risk of bias was assessed using the Office of Health Assessment and Translation tool (OHAT). A total of 17 eligible in vivo and in vitro studies were included in this review. Bone marrow-derived stem cells (BMSCs) were the most used source for exosome isolation, even though studies on exosomes from adipose-derived stem cells (ADSCs) and human umbilical cord stem cells (HUCSCs) provide more information on the characteristics. When the risk of bias was assessed, the studies presented various levels of biases. Notably, the in vitro and in vivo studies revealed neuroprotective properties of MSC-exosomes through different modes of action to alleviate AD pathology. Our review discovered that most MSC exosomes could degrade Aβ plaques, enhance neurogenesis, extenuate neuroinflammatory response through microglial activation, regulate apoptosis and reduce oxidative stress. Delivery of exosomal micro-RNAs was also found to reduce neuroinflammation. Findings from this review provided convincing systematic evidence highlighting the therapeutic properties of MSC-derived exosomes as a prospective source for cell-free (acellular) therapy in treating AD.
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Affiliation(s)
- Sarah Mohammed Yousuf Abdi
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia
| | - Siti Sarah Mustaffa Al-Bakri
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia
| | - Norshariza Nordin
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.
- Malaysian Research Institute on Ageing (MyAgeing™), Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
- Genetics & Regenerative Medicine (ReGEN) Research Group, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.
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Maria MKM, Abdel Moniem EM, Hanafy AK, Farag DBE, Radwan IA, Abbass MMS, El Moshy S, Rady D, Dörfer CE, Fawzy El-Sayed KM. Age-Related Oral and Para-Oral Tissue Disorders: The Evolving Therapeutic and Diagnostic Potential of Exosomes. Dent J (Basel) 2025; 13:106. [PMID: 40136734 PMCID: PMC11941486 DOI: 10.3390/dj13030106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/14/2025] [Accepted: 02/24/2025] [Indexed: 03/27/2025] Open
Abstract
This review highlights the key molecular and cellular mechanisms contributing to aging, such as DNA damage, mitochondrial dysfunction, telomere shortening, protein dysfunction, and defective autophagy. These biological mechanisms are involved in various oral health conditions prevalent in the elderly, including periodontal disease, oral cancer, xerostomia, dental caries, and temporomandibular joint disorders. Exosomes generated by mesenchymal stem cells possess substantial therapeutic potential. These exosomes are nanosized extracellular vesicles derived from cells and are involved in essential intercellular communication and tissue homeostasis. The exosome-based therapies proved superior to traditional cell-based approaches, due to lower immunogenicity, ease of storage, and avoidance of complications associated with cell transplantation. Furthermore, the diagnostic potential of exosomes as non-invasive biomarkers for aging processes and age-related oral diseases offers insights into disease diagnosis, staging, and monitoring. Among the challenges and future perspectives of translating exosome research from preclinical studies to clinical applications is the need for standardized procedures to fully harness the therapeutic and diagnostic capabilities of exosomes.
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Affiliation(s)
- Mohamed Khaled Mohamed Maria
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
| | | | - Ahmed Khaled Hanafy
- Oral Biology Department, Faculty of Dentistry, Egyptian Russian University, Badr City 11829, Egypt;
| | - Dina B. E. Farag
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
| | - Israa Ahmed Radwan
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Marwa M. S. Abbass
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Sara El Moshy
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Dina Rady
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Christof E. Dörfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, 24118 Kiel, Germany;
| | - Karim M. Fawzy El-Sayed
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, 24118 Kiel, Germany;
- Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt
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Shao YH, Song Y, Feng QL, Deng Y, Tang T. Assessing the Impact of Stem Cell-based Therapy on Periodontal Health: A Meta-analysis of Clinical Studies. Curr Stem Cell Res Ther 2025; 20:246-265. [PMID: 38347778 DOI: 10.2174/011574888x294900240130095058] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 01/13/2024] [Accepted: 01/24/2024] [Indexed: 05/13/2025]
Abstract
OBJECTIVE While clinical trials exploring stem cells for regenerating periodontal tissues have demonstrated positive results, there is a limited availability of systematic literature reviews on this subject. To gain a more comprehensive understanding of stem cell interventions in periodontal regeneration, this meta-analysis is undertaken to assess the beneficial effects of stem cells in human periodontal regeneration. METHODS "PubMed," "PubMed Central," "Web of Science," "Embase Scopus" "Wanfang," and "CNKI," were used to extract clinical studies related to the utilization of stem cells in repairing periodontal tissue defects. This search included studies published up until October 5, 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell-free therapy for regenerating periodontal tissues. Meta-analysis was conducted using Review Manager software (version 5.4). RESULTS This meta-analysis synthesized findings from 15 selected studies investigating the impact of stem cell interventions on periodontal tissue regeneration. The "stem cell" group displayed a substantial reduction in clinical attachment level (CAL) compared to the "control" group within 3 to 12 months post-surgery. However, no significant differences in CAL gain were found between groups. Probing pocket depth (PPD) significantly decreased in the "stem cell" group compared to the "control" group, particularly for follow-up periods exceeding 6 months, and dental stem cell treatment exhibited notable improvements. Conversely, no significant differences were observed in PPD reduction. Gingival recession (GR) significantly decreased in the "stem cell" group compared to the "control" group at 3 to 12 months post-surgery. No significant differences were observed in GR reduction between groups. No significant differences were identified in cementoenamel junction-bone distance reduction, infrabony defect reduction, or bone mineral density increase between the two groups. Furthermore, no significant changes were observed in the gingival index, plaque index, or width of keratinized gingiva. CONCLUSION In conclusion, while stem cell-based therapy offers promising prospects for periodontal defect treatment, there are notable limitations in the current body of research. Larger, multicenter, double-blind RCTs with robust methodologies are needed to provide more reliable evidence for stem cell-based intervention in periodontitis.
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Affiliation(s)
- Yu-Han Shao
- West China School of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Yi Song
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R., China
| | - Qiao-Li Feng
- Peking University Shenzhen Hospital, Peking University, Shenzhen, 518036, China
| | - Yan Deng
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R., China
| | - Tao Tang
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R., China
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Alavi SA, Imanian M, Alkaabi S, Al-Sabri G, Forouzanfar T, Helder M. A systematic review and meta-analysis on the use of regenerative graft materials for socket preservation in randomized clinical trials. Oral Surg Oral Med Oral Pathol Oral Radiol 2024; 138:702-718. [PMID: 39317600 DOI: 10.1016/j.oooo.2024.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 06/19/2024] [Accepted: 07/02/2024] [Indexed: 09/26/2024]
Abstract
OBJECTIVE To evaluate if regenerative materials with/without scaffold deployed in dental socket preservation led to reduced radiographic height and width bone resorption. STUDY DESIGN English-written human studies from January 2010 to December 2023 were selected from PubMed, EMBASE, MEDLINE, Cochrane CENTRAL, Google Scholar and manually searched journals. Six meta-analyses were conducted, addressing treatments with all blood-derived growth factor preparations as well as L-platelet-rich fibrin (L-PRF) separately, and recombinant human BMP-2 (rhBMP-2). An unpaired t-test on L-PRF and rhBMP-2 determined the clinically best preservation treatment. Cochrane risk of bias in all studies was analyzed. RESULTS Twenty-nine articles (1068 participants) were included. Meta-analyses on blood-derived preparations demonstrated nonsignificant alveolar width, but significant (p = .001) height preservation. L-PRF vs. natural healing demonstrated nonsignificant changes in both dimensions. RhBMP-2 caused highly significant reduced horizontal (p = .01) and vertical (p < .0008) bone resorptions. When comparing mean resorption rates, significant benefits of rhBMP-2 over L-PRF were observed for width but not height preservation (p < .0001 and p = .057, respectively). Six studies recorded low, 8 moderate, and 15 high net risks. CONCLUSIONS Regenerative materials appear beneficial for radiographic bone width and height preservation after tooth extraction. Although rhBMP-2 performed better in alveolar width preservation, L-PRF can be an autologous and cost-effective alternative.
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Affiliation(s)
- Seyed Abdolhojeh Alavi
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
| | - Mahsa Imanian
- Department of Oral and Maxillofacial Surgery, Leiden University Medical Centers, Universiteit Leiden, Leiden, Netherlands
| | - Salem Alkaabi
- Department of Oral and Maxillofacial Surgery, Fujairah Hospital, Emirates Health Services, United Arab Emirates, Department of Oral and Maxillofacial Surgery/Oral Pathology, Vrije Universiteit Amsterdam, Netherlands
| | - Ghamdan Al-Sabri
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Tim Forouzanfar
- Department of Oral and Maxillofacial Surgery, Leiden University Medical Centers, Universiteit Leiden, Leiden, Netherlands
| | - Marco Helder
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
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Ivanovski S, Han P, Peters O, Sanz M, Bartold P. The Therapeutic Use of Dental Mesenchymal Stem Cells in Human Clinical Trials. J Dent Res 2024; 103:1173-1184. [PMID: 39370700 PMCID: PMC11562285 DOI: 10.1177/00220345241261900] [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] [Indexed: 10/08/2024] Open
Abstract
Mesenchymal stem cells (MSCs), characterized by their undifferentiated and multipotent nature, can be derived from various sources, including bone marrow, adipose, and dental tissues. Among these, dental MSCs (DSCs) exhibit universal MSC characteristics and are attracting considerable attention for regenerating oral and craniofacial tissues. This review provides a contemporary overview of recently published clinical studies using DSCs for various orodental and maxillofacial regenerative applications, including bone, periodontal, and endodontic regeneration. It also explores the utilization of DSCs in treating systemic conditions, exemplified by their application in managing conditions such as COVID-19 and osteoarthritis. The available evidence underscores the potential of DSCs and their secretome as efficacious tools in regenerative medicine for both dental and nondental clinical applications, supporting the continued promise of stem cell-based therapies. It is nevertheless evident that there are a number of important challenges that restrict the widespread utilization of DSCs, namely, difficulty in standardizing autologous preparations, insufficient cell surface marker characterization, high production costs, and regulatory compliance requirements. Further, the unique requirements of dental applications, especially complex structures such as the periodontium, where temporospatial control over the healing process is required, necessitate the combination of stem cells with appropriate scaffolds according to the principles of tissue engineering. There is currently insufficient evidence to support the clinical translation of DSCs into clinical practice, and phase 3 clinical trials with standardized protocols for cell sourcing, propagation, dosing, and delivery are required to move the field forward. In summary, this review provides a contemporary overview of the evolving landscape of stem cell therapy, offering insights into the latest developments and trends as well as the challenges that need to be addressed for the widespread application of DSC-based cell therapies.
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Affiliation(s)
- S. Ivanovski
- The University of Queensland, School of Dentistry, Brisbane, QLD, Australia
| | - P. Han
- The University of Queensland, School of Dentistry, Brisbane, QLD, Australia
- The University of Queensland, School of Dentistry, Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), Brisbane, QLD, Australia
| | - O.A. Peters
- The University of Queensland, School of Dentistry, Brisbane, QLD, Australia
| | - M. Sanz
- ETEP (Etiology and Therapy of Periodontal and Peri-implant Diseases) Research Group, Faculty of Odontology, University Complutense of Madrid, Plaza Ramón y Cajalsn (Ciudad Universitaria), Madrid, Spain
| | - P.M. Bartold
- The University of Queensland, School of Dentistry, Brisbane, QLD, Australia
- The University of Adelaide, School of Dentistry, Adelaide, SA, Australia
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Kaigler D, Misch J, Alrmali A, Inglehart MR. Periodontists and stem cell-based therapy for alveolar bone regeneration: A national survey. J Periodontol 2024; 95:789-798. [PMID: 38196330 DOI: 10.1002/jper.23-0506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 11/06/2023] [Accepted: 11/06/2023] [Indexed: 01/11/2024]
Abstract
BACKGROUND Stem cell-based therapy for bone regeneration has received attention in medical settings but has not yet been used in clinical practice for treating alveolar bone defects. The objectives of this study were to explore whether periodontists had heard about this approach, and if so how, how interested they were to learn about it, which attitudes and behavioral intentions they had related to using stem cell-based grafting, and what they would like to know before using this approach. METHODS Anonymous survey data were collected from 481 members of the American Academy of Periodontology (response rate: 19.41%). RESULTS Responses showed 35.3% had heard about stem cell-based therapy, mostly from publications (9.6%) and meetings (8.3%); 76.1% wanted to learn about it through in-person continuing education (CE) courses, 68.6% in online CE courses, and 57.1% from manuals; 73% considered this approach promising; and 54.9% preferred it to traditional approaches. It was important to them that it would result in more bone volume (93%), better bone quality (90.4%), and accelerated healing (83.2%). Also, 60.1% considered it likely/very likely that they would adopt this approach, 54% that patients would prefer it, and 62.1% that it would benefit their practice. When asked what they would like to know about this approach, information about short- and long-term outcomes, cost, and logistical considerations were most frequently named. CONCLUSIONS These findings provide the basis to develop educational interventions for periodontists about this novel approach and inform future research activities aimed to translate this approach to clinical practice.
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Affiliation(s)
- Darnell Kaigler
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
- Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan, USA
| | - Jonathan Misch
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
| | - Abdusalam Alrmali
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
- Department of Oral Medicine, Oral Pathology, Oral and Maxillofacial Surgery, University of Tripoli School of Dentistry, Tripoli, Libya
| | - Marita R Inglehart
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
- Department of Psychology, College of Literature, Science and Arts (LS & A), University of Michigan, Ann Arbor, Michigan, USA
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Shah P, Aghazadeh M, Rajasingh S, Dixon D, Jain V, Rajasingh J. Stem cells in regenerative dentistry: Current understanding and future directions. J Oral Biosci 2024; 66:288-299. [PMID: 38403241 DOI: 10.1016/j.job.2024.02.006] [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: 01/09/2024] [Revised: 02/15/2024] [Accepted: 02/18/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND Regenerative dentistry aims to enhance the structure and function of oral tissues and organs. Modern tissue engineering harnesses cell and gene-based therapies to advance traditional treatment approaches. Studies have demonstrated the potential of mesenchymal stem cells (MSCs) in regenerative dentistry, with some progressing to clinical trials. This review comprehensively examines animal studies that have utilized MSCs for various therapeutic applications. Additionally, it seeks to bridge the gap between related findings and the practical implementation of MSC therapies, offering insights into the challenges and translational aspects involved in transitioning from preclinical research to clinical applications. HIGHLIGHTS To achieve this objective, we have focused on the protocols and achievements related to pulp-dentin, alveolar bone, and periodontal regeneration using dental-derived MSCs in both animal and clinical studies. Various types of MSCs, including dental-derived cells, bone-marrow stem cells, and umbilical cord stem cells, have been employed in root canals, periodontal defects, socket preservation, and sinus lift procedures. Results of such include significant hard tissue reconstruction, functional pulp regeneration, root elongation, periodontal ligament formation, and cementum deposition. However, cell-based treatments for tooth and periodontium regeneration are still in early stages. The increasing demand for stem cell therapies in personalized medicine underscores the need for scientists and responsible organizations to develop standardized treatment protocols that adhere to good manufacturing practices, ensuring high reproducibility, safety, and cost-efficiency. CONCLUSION Cell therapy in regenerative dentistry represents a growing industry with substantial benefits and unique challenges as it strives to establish sustainable, long-term, and effective oral tissue regeneration solutions.
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Affiliation(s)
- Pooja Shah
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Marziyeh Aghazadeh
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Sheeja Rajasingh
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Douglas Dixon
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA; Department of Periodontology, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Vinay Jain
- Department of Prosthodontics, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Johnson Rajasingh
- Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA; Department of Medicine-Cardiology, University of Tennessee Health Science Center, Memphis, TN, USA; Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA.
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Campagna A, Baima G, Romano F, Amoroso F, Mussano F, Oteri G, Aimetti M, Peditto M. Orally Derived Stem Cell-Based Therapy in Periodontal Regeneration: A Systematic Review and Meta-Analysis of Randomized Clinical Studies. Dent J (Basel) 2024; 12:145. [PMID: 38786543 PMCID: PMC11120617 DOI: 10.3390/dj12050145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 04/15/2024] [Accepted: 04/26/2024] [Indexed: 05/25/2024] Open
Abstract
The present systematic review was performed to assess the application of orally derived stem cells in periodontal regenerative therapy, and because of this, the following PICO question was proposed: "In patients with periodontitis, can the adjunctive use of orally derived stem cells provide additional clinical and radiographic benefits for periodontal regeneration?". Randomized clinical studies were electronically and manually searched up until December 2023. Quantitative analyses were performed with the aim of evaluating the mean differences (MDs) between the treatment and control groups in terms of clinical attachment level (CAL) gain, probing pocket depth (PPD) reduction, gingival recession (GR), and radiographic bone gain (RBG) using random effect models. A total of seven studies were selected for the systematic review. Meta-analyses excluding studies with a high risk of bias highlighted a non-statistically significant result for the use of stem cells when compared to the control groups in terms of CAL gain [MD = 1.05; 95% CI (-0.88, 2.97) p = 0.29] and PPD reduction [MD = 1.32; 95% CI (-0.25, 2.88) p = 0.10]. The same also applied to GR [MD = -0.08; 95% CI (-0.79, 0.63) p = 0.83] and RBG [MD = 0.50; 95% CI (-0.88, 1.88) p = 0.48]. Based on the high heterogeneity, there is not enough evidence to consider the adjunctive application of orally derived mesenchymal stem cells as a preferential approach for periodontal regenerative treatment, as compared to standard procedures.
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Affiliation(s)
- Alessandro Campagna
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98122 Messina, Italy; (A.C.); (G.O.); (M.P.)
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, 10126 Torino, Italy; (G.B.); (F.R.); (F.A.); (M.A.)
| | - Giacomo Baima
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, 10126 Torino, Italy; (G.B.); (F.R.); (F.A.); (M.A.)
| | - Federica Romano
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, 10126 Torino, Italy; (G.B.); (F.R.); (F.A.); (M.A.)
| | - Federico Amoroso
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, 10126 Torino, Italy; (G.B.); (F.R.); (F.A.); (M.A.)
- Politecnico di Torino, 10129 Torino, Italy
| | - Federico Mussano
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, 10126 Torino, Italy; (G.B.); (F.R.); (F.A.); (M.A.)
| | - Giacomo Oteri
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98122 Messina, Italy; (A.C.); (G.O.); (M.P.)
| | - Mario Aimetti
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, 10126 Torino, Italy; (G.B.); (F.R.); (F.A.); (M.A.)
| | - Matteo Peditto
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98122 Messina, Italy; (A.C.); (G.O.); (M.P.)
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9
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Zheng Z, Liu H, Liu S, Luo E, Liu X. Mesenchymal stem cells in craniofacial reconstruction: a comprehensive review. Front Mol Biosci 2024; 11:1362338. [PMID: 38690295 PMCID: PMC11058977 DOI: 10.3389/fmolb.2024.1362338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 03/29/2024] [Indexed: 05/02/2024] Open
Abstract
Craniofacial reconstruction faces many challenges, including high complexity, strong specificity, severe injury, irregular and complex wounds, and high risk of bleeding. Traditionally, the "gold standard" for treating craniofacial bone defects has been tissue transplantation, which involves the transplantation of bone, cartilage, skin, and other tissues from other parts of the body. However, the shape of craniofacial bone and cartilage structures varies greatly and is distinctly different from ordinary long bones. Craniofacial bones originate from the neural crest, while long bones originate from the mesoderm. These factors contribute to the poor effectiveness of tissue transplantation in repairing craniofacial defects. Autologous mesenchymal stem cell transplantation exhibits excellent pluripotency, low immunogenicity, and minimally invasive properties, and is considered a potential alternative to tissue transplantation for treating craniofacial defects. Researchers have found that both craniofacial-specific mesenchymal stem cells and mesenchymal stem cells from other parts of the body have significant effects on the restoration and reconstruction of craniofacial bones, cartilage, wounds, and adipose tissue. In addition, the continuous development and application of tissue engineering technology provide new ideas for craniofacial repair. With the continuous exploration of mesenchymal stem cells by researchers and the continuous development of tissue engineering technology, the use of autologous mesenchymal stem cell transplantation for craniofacial reconstruction has gradually been accepted and promoted. This article will review the applications of various types of mesenchymal stem cells and related tissue engineering in craniofacial repair and reconstruction.
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Affiliation(s)
| | | | | | - En Luo
- State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Xian Liu
- State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
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10
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Setiawan J, Rizal DM, Sofyantoro F, Priyono DS, Septriani NI, Mafiroh WU, Kotani T, Matozaki T, Putri WA. Bibliometric analysis of organoids in regenerative medicine-related research worldwide over two decades (2002-2022). Regen Med 2024; 19:119-133. [PMID: 38449425 DOI: 10.2217/rme-2023-0176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2024] Open
Abstract
Aim: This study aimed to evaluate the trends in organoid culture research within the field of regenerative medicine from 2002 to 2022. Methods: The worldwide distribution of organoid research in regenerative medicine articles indexed in the Scopus database was analyzed. Result: A total of 840 documents were analyzed, averaging 42 publications annually. The USA (n = 296) led in publications, followed by China (n = 127), Japan (n = 91) and the UK (n = 75). Since 2011, research has surged, particularly in China, which emerged as a prominent center. Conclusion: The findings highlight significant growth in organoid research, promising future organ transplantation. Research trends integrate tissue engineering, gene modification and induced pluripotent stem cell technologies, reflecting a move toward personalized medicine.
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Affiliation(s)
- Jajar Setiawan
- Department of Physiology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Dicky Moch Rizal
- Department of Physiology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Fajar Sofyantoro
- Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Dwi Sendi Priyono
- Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Nur Indah Septriani
- Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Wulan Usfi Mafiroh
- Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Takenori Kotani
- Division of Molecular and Cellular Signaling, Department of Biochemistry & Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takashi Matozaki
- Division of Molecular and Cellular Signaling, Department of Biochemistry & Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan
- Division of Biosignal Regulation, Department of Biochemistry & Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Wahyu Aristyaning Putri
- Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
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11
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Jang HJ, Yoon JK. The Role of Vasculature and Angiogenic Strategies in Bone Regeneration. Biomimetics (Basel) 2024; 9:75. [PMID: 38392121 PMCID: PMC10887147 DOI: 10.3390/biomimetics9020075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 01/18/2024] [Accepted: 01/22/2024] [Indexed: 02/24/2024] Open
Abstract
Bone regeneration is a complex process that involves various growth factors, cell types, and extracellular matrix components. A crucial aspect of this process is the formation of a vascular network, which provides essential nutrients and oxygen and promotes osteogenesis by interacting with bone tissue. This review provides a comprehensive discussion of the critical role of vasculature in bone regeneration and the applications of angiogenic strategies, from conventional to cutting-edge methodologies. Recent research has shifted towards innovative bone tissue engineering strategies that integrate vascularized bone complexes, recognizing the significant role of vasculature in bone regeneration. The article begins by examining the role of angiogenesis in bone regeneration. It then introduces various in vitro and in vivo applications that have achieved accelerated bone regeneration through angiogenesis to highlight recent advances in bone tissue engineering. This review also identifies remaining challenges and outlines future directions for research in vascularized bone regeneration.
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Affiliation(s)
- Hye-Jeong Jang
- Department of Systems Biotechnology, Chung-Ang University, Anseong-si 17546, Gyeonggi-do, Republic of Korea
| | - Jeong-Kee Yoon
- Department of Systems Biotechnology, Chung-Ang University, Anseong-si 17546, Gyeonggi-do, Republic of Korea
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12
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Zhang W, Kohn J, Yelick PC. TyroFill-Titanium Implant Constructs for the Coordinated Repair of Rabbit Mandible and Tooth Defects. Bioengineering (Basel) 2023; 10:1277. [PMID: 38002402 PMCID: PMC10668976 DOI: 10.3390/bioengineering10111277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 10/03/2023] [Accepted: 10/13/2023] [Indexed: 11/26/2023] Open
Abstract
Currently used methods to repair craniomaxillofacial (CMF) bone and tooth defects require a multi-staged surgical approach for bone repair followed by dental implant placement. Our previously published results demonstrated significant bioengineered bone formation using human dental pulp stem cell (hDPSC)-seeded tyrosine-derived polycarbonate scaffolds (E1001(1K)-bTCP). Here, we improved upon this approach using a modified TyroFill (E1001(1K)/dicalcium phosphate dihydrate (DCPD)) scaffold-supported titanium dental implant model for simultaneous bone-dental implant repair. TyroFill scaffolds containing an embedded titanium implant, with (n = 3 each time point) or without (n = 2 each time point) seeded hDPCs and Human Umbilical Vein Endothelial Cells (HUVECs), were cultured in vitro. Each implant was then implanted into a 10 mm full-thickness critical-sized defect prepared on a rabbit mandibulee. After 1 and 3 months, replicate constructs were harvested and analyzed using Micro-CT histological and IHC analyses. Our results showed significant new bone formation surrounding the titanium implants in cell-seeded TyroFill constructs. This study indicates the potential utility of hDPSC/HUVEC-seeded TyroFill scaffolds for coordinated CMF bone-dental implant repair.
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Affiliation(s)
- Weibo Zhang
- Department of Orthodontics, Division of Craniofacial and Molecular Genetics, Tufts University School of Dental Medicine, Boston, MA 02111, USA
| | - Joachim Kohn
- New Jersey Center for Biomaterials, Rutgers University, Piscataway, NJ 08854, USA
| | - Pamela C. Yelick
- Department of Orthodontics, Division of Craniofacial and Molecular Genetics, Tufts University School of Dental Medicine, Boston, MA 02111, USA
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Yu Z, Jiang X, Yin J, Han L, Xiong C, Huo Z, Xu J, Shang J, Xi K, Nong L, Huang Y, Zhou X. CK1ε drives osteogenic differentiation of bone marrow mesenchymal stem cells via activating Wnt/β-catenin pathway. Aging (Albany NY) 2023; 15:10193-10212. [PMID: 37787983 PMCID: PMC10599756 DOI: 10.18632/aging.205067] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Accepted: 09/08/2023] [Indexed: 10/04/2023]
Abstract
The treatment of bone defects is a difficult problem in orthopedics. At present, the treatment mainly relies on autologous or allogeneic bone transplantation, which may lead to some complications such as foreign body rejection, local infection, pain, or numbness at the bone donor site. Local injection of conservative therapy to treat bone defects is one of the research hotspots at present. Bone marrow mesenchymal stem cells (BMSCs) can self-renew, significantly proliferate, and differentiate into various types of cells. Although it has been reported that CK1ε could mediate the Wnt/β-catenin pathway, leading to the development of the diseases, whether CK1ε plays a role in bone regeneration through the Wnt/β-catenin pathway has rarely been reported. The purpose of this study was to investigate whether CK1ε was involved in the osteogenic differentiation (OD) of BMSCs through the Wnt/β-catenin pathway and explore the mechanism. We used quantitative reverse transcription-polymerase chain reaction (qRT-qPCR), Western blots, immunofluorescence, alkaline phosphatase, and alizarin red staining to detect the effect of CK1ε on the OD of BMSCs and the Wnt/β-catenin signaling pathway. CK1ε was highly expressed in BMSCs with OD, and our study further demonstrated that CK1ε might promote the OD of BMSCs by activating DLV2 phosphorylation, initiating Wnt signaling downstream, and activating β-catenin nuclear transfer. In addition, by locally injecting a CK1ε-carrying adeno-associated virus (AAV5- CK1ε) into a femoral condyle defect rat model, the overexpression of CK1ε significantly promoted bone repair. Our data show that CK1ε was involved in the regulation of OD by mediating Wnt/β-catenin. This may provide a new strategy for the treatment of bone defects.
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Affiliation(s)
- Zhentang Yu
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, China
- Department of Orthopedics, Yibin Integrated Traditional Chinese and Western Medicine Hospital, Yibin 644104, China
- Department of Graduate School, Dalian Medical University, Dalian 116000, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
| | - Xijia Jiang
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
| | - Jianjian Yin
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
| | - Lei Han
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, China
- Department of Graduate School, Dalian Medical University, Dalian 116000, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
| | - Chengwei Xiong
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, China
- Department of Graduate School, Dalian Medical University, Dalian 116000, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
| | - Zhennan Huo
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, China
- Department of Graduate School, Dalian Medical University, Dalian 116000, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
| | - Jie Xu
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
| | - Jingjing Shang
- Department of Pharmacy, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, China
| | - Kun Xi
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou 215006, China
| | - Luming Nong
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
| | - Yong Huang
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
| | - Xindie Zhou
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, China
- Department of Orthopedics, Gonghe County Hospital of Traditional Chinese Medicine, Hainan Tibetan Autonomous Prefecture, Qinghai 811800, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
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14
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Liu X, Lv S, Kan W, Fan B, Shao B. Human alveolar bone-derived mesenchymal stem cell cultivation on a 3D-printed PDLLA scaffold for bone formation. Br J Oral Maxillofac Surg 2023; 61:527-533. [PMID: 37679196 DOI: 10.1016/j.bjoms.2023.07.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 07/20/2023] [Accepted: 07/31/2023] [Indexed: 09/09/2023]
Abstract
This study aimed to assess effects of 3-dimensionally (3D) printed poly-d,l-lactin (PDLLA) on human alveolar bone-derived mesenchymal stem cell (h-ABMSC) osteogenic proliferation and differentiation. Human ABMSCs were cultured and identified using flow cytometry and morphological analysis. Control and PDLLA experimental groups were assessed using a Cell Counting Kit-8 (CCK-8) to detect cellular cytotoxicity and proliferative activity. Real-time quantitative polymerase chain reaction was used to determine expression levels of osteogenesis genes including alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx-2), osteopontin (OPN), and osteocalcin (OCN). The results showed that h-ABMSCs were successfully cultured and revealed by microscopic observation. Human ABMSCs were spindle-shaped, with clustered and fish-like primary cells. Cell surface markers were negative for CD34 and positive for CD44 and CD90. PDLLA had no cytotoxicity. Human ABMSCs proliferated normally, and osteogenic differentiation of the cells was observed on the surface of PDLLA. Cellular proliferative activity and expression levels of osteogenesis-related genes of PDLLA and control groups showed no significant difference, including ALP, Runx-2, OPN, and OCN. These results suggest that 3D-printed PDLLA has good cell compatibility and biological activity.
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Affiliation(s)
- Xu Liu
- Department of Stomatology, Baoding First Central Hospital, 320 Great Wall North Street, Baoding 071000, Hebei, China
| | - Shouyin Lv
- Department of Stomatology, Inner Mongolia Autonomous Region People's Hospital, 20 Zhaowuda Road, Huhhot 010017, Inner Mongolia, China
| | - Wenjiao Kan
- Department of Stomatology, Inner Mongolia Autonomous Region People's Hospital, 20 Zhaowuda Road, Huhhot 010017, Inner Mongolia, China
| | - Boxi Fan
- Department of Stomatology, Inner Mongolia Autonomous Region People's Hospital, 20 Zhaowuda Road, Huhhot 010017, Inner Mongolia, China
| | - Bo Shao
- Department of Stomatology, Inner Mongolia Autonomous Region People's Hospital, 20 Zhaowuda Road, Huhhot 010017, Inner Mongolia, China.
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15
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Nguyen-Thi TD, Nguyen-Huynh BH, Vo-Hoang TT, Nguyen-Thanh T. Stem cell therapies for periodontal tissue regeneration: A meta-analysis of clinical trials. J Oral Biol Craniofac Res 2023; 13:589-597. [PMID: 37576801 PMCID: PMC10415796 DOI: 10.1016/j.jobcr.2023.07.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 07/04/2023] [Indexed: 08/15/2023] Open
Abstract
Objective Stem cell therapy in periodontal tissue regeneration has reported optimistic regenerative results; evidence supporting its superiority over conventional methods is still ambiguous. Therefore, this meta-analysis aims to evaluate the therapeutic effects of stem cells in human periodontal regeneration. Design A literature search was conducted to retrieve relevant articles on periodontal regeneration in stem cell therapy. A meta-analysis of the studies was conducted using the Stata software. Results Fifteen studies that examined the effect of stem cell therapies on periodontal tissue regeneration in 369 patients were selected from databases. Regardless of the various types of cells, both odontogenic (periodontal ligament, dental pulp, gingiva stem cell) and non-odontogenic (bone marrow, periosteum-derived, and umbilical cord stem cells), the cell therapies witnessed significant improvements in terms of clinical attachment level (SMD, -0.67; 95CI, -0.90 to -0.43), probing depth (SMD, -0.76; 95% CI, -1.21 to - 0.31), radiographic intrabony defect depth (SMD, -0.87; 95% CI, -1.52 to -0.23), and histomorphometric analysis of mineralized bone (SMD, 0.80; 95% CI, 0.42 to 1.19) when compared to traditional without-cell treatment in patients. However, evidence on gingival recession, alveolar thickness gain, bone mineral density of bone core, and bone volume fraction of bone core outcomes did not reach statistical significance. Conclusions Evidence suggests that the implementation of stem cell therapies in reconstructing compromised gingiva and alveolar bone tissue produces positive outcomes compared with conventional approaches. However, further well-designed investigations are needed to comprehensively identify the most effective source of cells and biomaterials for each case.
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Affiliation(s)
- Thuy-Duong Nguyen-Thi
- Odonto-stomatology Faculty, University of Medicine and Pharmacy, Hue University, 6 Ngo Quyen Street, Hue, 49000, Viet Nam
| | - Bao-Hung Nguyen-Huynh
- Odonto-stomatology Faculty, University of Medicine and Pharmacy, Hue University, 6 Ngo Quyen Street, Hue, 49000, Viet Nam
| | - Thuy-Tien Vo-Hoang
- Odonto-stomatology Faculty, University of Medicine and Pharmacy, Hue University, 6 Ngo Quyen Street, Hue, 49000, Viet Nam
| | - Tung Nguyen-Thanh
- Faculty of Basic Science, University of Medicine and Pharmacy, Hue University, 6 Ngo Quyen Street, Hue, 49000, Viet Nam
- Institute of Biomedicine, University of Medicine and Pharmacy, Hue University, 6 Ngo Quyen Street, Hue, 49000, Viet Nam
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Tahmasebi E, Mohammadi M, Alam M, Abbasi K, Gharibian Bajestani S, Khanmohammad R, Haseli M, Yazdanian M, Esmaeili Fard Barzegar P, Tebyaniyan H. The current regenerative medicine approaches of craniofacial diseases: A narrative review. Front Cell Dev Biol 2023; 11:1112378. [PMID: 36926524 PMCID: PMC10011176 DOI: 10.3389/fcell.2023.1112378] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 02/08/2023] [Indexed: 03/08/2023] Open
Abstract
Craniofacial deformities (CFDs) develop following oncological resection, trauma, or congenital disorders. Trauma is one of the top five causes of death globally, with rates varying from country to country. They result in a non-healing composite tissue wound as they degenerate in soft or hard tissues. Approximately one-third of oral diseases are caused by gum disease. Due to the complexity of anatomical structures in the region and the variety of tissue-specific requirements, CFD treatments present many challenges. Many treatment methods for CFDs are available today, such as drugs, regenerative medicine (RM), surgery, and tissue engineering. Functional restoration of a tissue or an organ after trauma or other chronic diseases is the focus of this emerging field of science. The materials and methodologies used in craniofacial reconstruction have significantly improved in the last few years. A facial fracture requires bone preservation as much as possible, so tiny fragments are removed initially. It is possible to replace bone marrow stem cells with oral stem cells for CFDs due to their excellent potential for bone formation. This review article discusses regenerative approaches for different types of craniofacial diseases.
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Affiliation(s)
- Elahe Tahmasebi
- Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mehdi Mohammadi
- School of Dentistry, Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Mostafa Alam
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kamyar Abbasi
- Department of Prosthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeed Gharibian Bajestani
- Student Research Committee, Dentistry Research Center, Research Institute of Dental Sciences, Dental School, Shahid Behesti University of Medical Sciences, Tehran, Iran
| | - Rojin Khanmohammad
- Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Mohsen Haseli
- Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Mohsen Yazdanian
- Research Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | | | - Hamid Tebyaniyan
- Department of Science and Research, Islimic Azade University, Tehran, Iran
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Tavelli L, Barootchi S, Rasperini G, Giannobile WV. Clinical and patient-reported outcomes of tissue engineering strategies for periodontal and peri-implant reconstruction. Periodontol 2000 2023; 91:217-269. [PMID: 36166659 PMCID: PMC10040478 DOI: 10.1111/prd.12446] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 05/25/2022] [Accepted: 06/05/2022] [Indexed: 11/28/2022]
Abstract
Scientific advancements in biomaterials, cellular therapies, and growth factors have brought new therapeutic options for periodontal and peri-implant reconstructive procedures. These tissue engineering strategies involve the enrichment of scaffolds with living cells or signaling molecules and aim at mimicking the cascades of wound healing events and the clinical outcomes of conventional autogenous grafts, without the need for donor tissue. Several tissue engineering strategies have been explored over the years for a variety of clinical scenarios, including periodontal regeneration, treatment of gingival recessions/mucogingival conditions, alveolar ridge preservation, bone augmentation procedures, sinus floor elevation, and peri-implant bone regeneration therapies. The goal of this article was to review the tissue engineering strategies that have been performed for periodontal and peri-implant reconstruction and implant site development, and to evaluate their safety, invasiveness, efficacy, and patient-reported outcomes. A detailed systematic search was conducted to identify eligible randomized controlled trials reporting the outcomes of tissue engineering strategies utilized for the aforementioned indications. A total of 128 trials were ultimately included in this review for a detailed qualitative analysis. Commonly performed tissue engineering strategies involved scaffolds enriched with mesenchymal or somatic cells (cell-based tissue engineering strategies), or more often scaffolds loaded with signaling molecules/growth factors (signaling molecule-based tissue engineering strategies). These approaches were found to be safe when utilized for periodontal and peri-implant reconstruction therapies and implant site development. Tissue engineering strategies demonstrated either similar or superior clinical outcomes than conventional approaches for the treatment of infrabony and furcation defects, alveolar ridge preservation, and sinus floor augmentation. Tissue engineering strategies can promote higher root coverage, keratinized tissue width, and gingival thickness gain than scaffolds alone can, and they can often obtain similar mean root coverage compared with autogenous grafts. There is some evidence suggesting that tissue engineering strategies can have a positive effect on patient morbidity, their preference, esthetics, and quality of life when utilized for the treatment of mucogingival deformities. Similarly, tissue engineering strategies can reduce the invasiveness and complications of autogenous graft-based staged bone augmentation. More studies incorporating patient-reported outcomes are needed to understand the cost-benefits of tissue engineering strategies compared with traditional treatments.
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Affiliation(s)
- Lorenzo Tavelli
- Division of Periodontology, Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
- Center for Clinical Research and Evidence Synthesis in Oral Tissue Regeneration (CRITERION), Boston, Massachusetts, USA
| | - Shayan Barootchi
- Center for Clinical Research and Evidence Synthesis in Oral Tissue Regeneration (CRITERION), Boston, Massachusetts, USA
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
| | - Giulio Rasperini
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- IRCCS Foundation Polyclinic Ca’ Granda, University of Milan, Milan, Italy
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18
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Liu C, Sharpe P, Volponi AA. Applications of regenerative techniques in adult orthodontics. FRONTIERS IN DENTAL MEDICINE 2023. [DOI: 10.3389/fdmed.2022.1100548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Management of the growing adult orthodontic patient population must contend with challenges particular to orthodontic treatment in adults. These include a limited rate of tooth movement, increased incidence of periodontal complications, higher risk of iatrogenic root resorption and pulp devitalisation, resorbed edentulous ridges, and lack of growth potential. The field of regenerative dentistry has evolved numerous methods of manipulating cellular and molecular processes to rebuild functional oral and dental tissues, and research continues to advance our understanding of stem cells, signalling factors that stimulate repair and extracellular scaffold interactions for the purposes of tissue engineering. We discuss recent findings in the literature to synthesise our understanding of current and prospective approaches based on biological repair that have the potential to improve orthodontic treatment outcomes in adult patients. Methods such as mesenchymal stem cell transplantation, biomimetic scaffold manipulation, and growth factor control may be employed to overcome the challenges described above, thereby reducing adverse sequelae and improving orthodontic treatment outcomes in adult patients. The overarching goal of such research is to eventually translate these regenerative techniques into clinical practice, and establish a new gold standard of safe, effective, autologous therapies.
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Regenerative Potential of Granulation Tissue in Periodontitis: A Systematic Review and Meta-analysis. Stem Cells Int 2023; 2023:8789852. [PMID: 36926181 PMCID: PMC10014158 DOI: 10.1155/2023/8789852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/27/2022] [Accepted: 02/15/2023] [Indexed: 03/12/2023] Open
Abstract
Methods Electronic searches were conducted in five databases including CENTRAL, MEDLINE, EMBASE, Web of Science, and Dentistry & Oral Sciences Source using a combination of MeSH terms and keywords up to 21 June 2022. Human studies including patients aged over 18 years with all forms of periodontitis were included. Following the risk of bias assessment, both qualitative and quantitative analyses were performed. Results A total of twelve studies were included in qualitative analysis and six of them in quantitative analyses. The evidence suggested that cells derived from periodontitis granulation tissue have osteogenic, adipogenic, chondrogenic, neurogenic, and angiogenic differentiation abilities as well as immunoregulatory properties. In particular, CD44+, CD73+, CD90+, CD105+, and CD146+ cells were found widely in granulation tissue whilst the only meta-analysis confirmed that CD90+ cells were present in lower numbers within the granulation tissue when compared with healthy periodontal tissue (WMD = -23.43%, 95% CI -30.43 to -16.44, p < 0.00001). Conclusions This review provided further evidence that granulation tissue from patients with periodontitis can be a potential stem cell source for regenerative therapy.
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Song W, Bo X, Ma X, Hou K, Li D, Geng W, Zeng J. Craniomaxillofacial derived bone marrow mesenchymal stem/stromal cells (BMSCs) for craniomaxillofacial bone tissue engineering: A literature review. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2022; 123:e650-e659. [PMID: 35691558 DOI: 10.1016/j.jormas.2022.06.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 04/06/2022] [Accepted: 06/07/2022] [Indexed: 11/20/2022]
Abstract
Craniomaxillofacial bone defects seriously affect the appearance, function, and psychological status of patients. Traditional autologous bone grafting is very challenging due to the limited sources of bone tissue, excessive surgical trauma, and high incidence of related complications. Craniomaxillofacial bone tissue engineering (BTE) strategies based on bone marrow mesenchymal stem cells (BMSCs) are emerging as an alternative. Craniomaxillofacial BMSCs (C-BMSCs) are homologous to craniomaxillofacial bones, which develop from the mesoderm and neural crest. This article aims to compare the differences in osteogenesis, angiogenesis, and immune regulation of C-BMSCs and other sources of BMSCs, and propose ideas and strategies such as 3D printing and mechanotherapy to completely harness the characteristics of C-BMSCs. In conclusion, C-BSMCs are a promising source of stem cells for the repair and reconstruction of craniomaxillofacial bone defects, and more attention should be paid to accelerating their basic research and clinical practices.
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Affiliation(s)
- Wenpeng Song
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
| | - Xiaowen Bo
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Xiaohan Ma
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
| | - Kegui Hou
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China; Department of Stomatology, Shunyi District Hospital affiliated to Capital Medical University, Beijing, China
| | - Dan Li
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
| | - Wei Geng
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
| | - Jianyu Zeng
- Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.
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Zhou YH, Guo Y, Zhu JY, Tang CY, Zhao YQ, Zhou HD. Spheroid co-culture of BMSCs with osteocytes yields ring-shaped bone-like tissue that enhances alveolar bone regeneration. Sci Rep 2022; 12:14636. [PMID: 36030312 PMCID: PMC9420131 DOI: 10.1038/s41598-022-18675-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 08/17/2022] [Indexed: 11/09/2022] Open
Abstract
Oral and maxillofacial bone defects severely impair appearance and function, and bioactive materials are urgently needed for bone regeneration. Here, we spheroid co-cultured green fluorescent protein (GFP)-labeled bone marrow stromal cells (BMSCs) and osteocyte-like MLO-Y4 cells in different ratios (3:1, 2:1, 1:1, 1:2, 1:3) or as monoculture. Bone-like tissue was formed in the 3:1, 2:1, and 1:1 co-cultures and MLO-Y4 monoculture. We found a continuous dense calcium phosphate structure and spherical calcium phosphate similar to mouse femur with the 3:1, 2:1, and 1:1 co-cultures, along with GFP-positive osteocyte-like cells encircled by an osteoid-like matrix similar to cortical bone. Flake-like calcium phosphate, which is more mature than spherical calcium phosphate, was found with the 3:1 and 2:1 co-cultures. Phosphorus and calcium signals were highest with 3:1 co-culture, and this bone-like tissue was ring-shaped. In a murine tooth extraction model, implantation of the ring-shaped bone-like tissue yielded more bone mass, osteoid and mineralized bone, and collagen versus no implantation. This tissue fabricated by spheroid co-culturing BMSCs with osteocytes yields an internal structure and mineral composition similar to mouse femur and could promote bone formation and maturation, accelerating regeneration. These findings open the way to new strategies in bone tissue engineering.
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Affiliation(s)
- Ying-Hui Zhou
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.,Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Yue Guo
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.,Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Jia-Yu Zhu
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Chen-Yi Tang
- Department of Nutrition, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China
| | - Ya-Qiong Zhao
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Hou-De Zhou
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
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22
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Amiri MA, Farshidfar N, Hamedani S. The feasibility of craniofacial-derived bone marrow stem cells for the treatment of oral and maxillofacial hard tissue defects. J Dent Sci 2022; 17:1445-1447. [PMID: 35784165 PMCID: PMC9236948 DOI: 10.1016/j.jds.2022.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/11/2022] [Indexed: 11/23/2022] Open
Affiliation(s)
- Mohammad Amin Amiri
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nima Farshidfar
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Orthodontic Research Center, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shahram Hamedani
- Oral and Dental Disease Research Center, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
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23
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Migration and phenotype switching of macrophages at early-phase of bone-formation by secretomes from bone marrow derived mesenchymal stem cells using rat calvaria bone defect model. J Dent Sci 2022; 17:421-429. [PMID: 35028066 PMCID: PMC8739749 DOI: 10.1016/j.jds.2021.08.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 08/17/2021] [Indexed: 01/08/2023] Open
Abstract
Background/purpose Conditioned media of cultured mesenchymal stem cells (MSCs) contain numerous kinds of secretomes such as cytokines and chemokines. We previously reported that conditioned media of bone marrow-derived MSCs (MSC-CM) promote bone formation. Recently, macrophage phenotype switching from the pro-inflammatory M1 type to the anti-inflammatory M2 type has been reported to be an important phenomenon during tissue regeneration. Some studies reported that this phenotype switching is regulated by secretomes. In this study, macrophage phenotype during bone formation by MSC-CM was investigated. Materials and methods Human MSCs (hMSCs) were cultured in serum-free medium and the collected medium was defined as MSC-CM. Macrophage-related gene expressions in hMSCs cultured with MSC-CM were evaluated by quantitative real-time polymerase chain reaction. MSC-CM was implanted and the evaluations by micro-CT and immunohistochemistry were performed using a rat the calvaria bone defect model. Results Two and four weeks after implantation, the MSC-CM group demonstrated enhanced bone regeneration. Gene expressions of C–C motif chemokine 2 (CCL2), colony-stimulating factor 2 (CSF2) and CD163 was significantly upregulated in cells exposed to MSC-CM. Immunohistochemical staining revealed that iNOS-positive M1 macrophages were reduced, while CD204-positive M2 macrophages were increased in the MSC-CM group at 72 h after implantation, and the M2/M1 ratio increased only in the MSC-CM group. Conclusion MSC-CM enhances macrophage migration and induces M1 to M2 type macrophage switching at an early stage of osteogenesis. Such phenotype switching provides a favorable environment for angiogenesis, cellular migration, and osteogenesis and contributes to MSC-CM-induced early bone formation.
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24
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Zou D, Vigen M, Putnam AJ, Cao C, Tarlé SA, Guinn T, Kaigler D. Phenotypic, trophic, and regenerative properties of mesenchymal stem cells from different osseous tissues. Cell Tissue Res 2022; 388:75-88. [DOI: 10.1007/s00441-021-03563-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 11/16/2021] [Indexed: 12/18/2022]
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Xian J, Liang D, Zhao C, Chen Y, Zhu Q. TRIM21 inhibits the osteogenic differentiation of mesenchymal stem cells by facilitating K48 ubiquitination-mediated degradation of Akt. Exp Cell Res 2022; 412:113034. [DOI: 10.1016/j.yexcr.2022.113034] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/11/2022] [Accepted: 01/13/2022] [Indexed: 01/18/2023]
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26
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Extracellular Vesicles in Musculoskeletal Regeneration: Modulating the Therapy of the Future. Cells 2021; 11:cells11010043. [PMID: 35011605 PMCID: PMC8750529 DOI: 10.3390/cells11010043] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/20/2021] [Accepted: 12/22/2021] [Indexed: 12/12/2022] Open
Abstract
Tissue regeneration is a hot topic in health sciences, particularly because effective therapies promoting the healing of several cell types are lacking, specifically those of the musculoskeletal system. Mesenchymal Stem/Stromal Cells (MSCs) have been identified as crucial players in bone homeostasis, and are considered a promising therapy for diseases such as osteoarthritis (OA) and Rheumatoid Arthritis (RA). However, some known drawbacks limit their use, particularly ethical issues and immunological rejections. Thus, MSCs byproducts, namely Extracellular Vesicles (EVs), are emerging as potential solutions to overcome some of the issues of the original cells. EVs can be modulated by either cellular preconditioning or vesicle engineering, and thus represent a plastic tool to be implemented in regenerative medicine. Further, the use of biomaterials is important to improve EV delivery and indirectly to modulate their content and secretion. This review aims to connect the dots among MSCs, EVs, and biomaterials, in the context of musculoskeletal diseases.
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27
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Asahina I, Kagami H, Agata H, Honda MJ, Sumita Y, Inoue M, Nagamura-Inoue T, Tojo A. Clinical Outcome and 8-Year Follow-Up of Alveolar Bone Tissue Engineering for Severely Atrophic Alveolar Bone Using Autologous Bone Marrow Stromal Cells with Platelet-Rich Plasma and β-Tricalcium Phosphate Granules. J Clin Med 2021; 10:jcm10225231. [PMID: 34830513 PMCID: PMC8623501 DOI: 10.3390/jcm10225231] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/31/2021] [Accepted: 11/08/2021] [Indexed: 01/02/2023] Open
Abstract
Background: Although bone tissue engineering for dentistry has been studied for many years, the clinical outcome for severe cases has not been established. Furthermore, there are limited numbers of studies that include long-term follow-up. In this study, the safety and efficacy of bone tissue engineering for patients with a severely atrophic alveolar bone were examined using autogenous bone marrow stromal cells (BMSCs), and the long-term stability was also evaluated. Methods: BMSCs from iliac bone marrow aspirate were cultured and expanded. Then, induced osteogenic cells were transplanted with autogenous platelet-rich plasma (PRP) and β-tricalcium phosphate granules (β-TCP) for maxillary sinus floor and alveolar ridge augmentation. Eight patients (two males and six females) with an average age of 54.2 years underwent cell transplantation. Safety was assessed by monitoring adverse events. Radiographic evaluation and bone biopsies were performed to evaluate the regenerated bone. Results: The major population of transplanted BMSCs belonged to the fraction of CD34−, CD45dim, and CD73+ cells, which was only 0.065% of the total bone marrow cells. Significant deviations were observed in cell growth and alkaline phosphatase activities among individuals. However, bone regeneration was observed in all patients and the average bone area in the biopsy samples was 41.9% 6 months following transplantation, although there were also significant deviations among each case. No adverse events related to the transplants were observed. In the regenerated bone, 27 out of 29 dental implants were integrated. Dental implants and regenerated bone were stable for an average follow-up period of 7 years and 10 months. Conclusions: Although individual variations were observed, the results showed that bone tissue engineering using BMSCs with PRP and β-TCP was feasible for patients with severe atrophic maxilla throughout a long-term follow-up period and was considered safe. However, further studies with a larger number of cases and controls to confirm the efficacy of BMSCs and the development of a protocol to establish a reproducible quality of stem cell-based graft material will be required.
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Affiliation(s)
- Izumi Asahina
- Division of Stem Cell Engineering, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
- Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan
| | - Hideaki Kagami
- Division of Stem Cell Engineering, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
- Tissue Engineering Research Group, Division of Molecular Therapy, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
- Department of Oral and Maxillofacial Surgery, Matsumoto Dental University, Shiojiri 399-0781, Japan
| | - Hideki Agata
- Division of Stem Cell Engineering, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
- Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan
| | - Masaki J Honda
- Division of Stem Cell Engineering, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
- Department of Oral Anatomy, Aichi-Gakuin University School of Dentistry, Nagoya 464-0821, Japan
| | - Yoshinori Sumita
- Division of Stem Cell Engineering, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
- Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan
| | - Minoru Inoue
- Tissue Engineering Research Group, Division of Molecular Therapy, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
- Department of Oral and Maxillofacial Surgery, Matsumoto Dental University, Shiojiri 399-0781, Japan
| | - Tokiko Nagamura-Inoue
- Department of Cell Processing and Transfusion, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Arinobu Tojo
- Tissue Engineering Research Group, Division of Molecular Therapy, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
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28
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Alkaabi SA, Alsabri GA, NatsirKalla DS, Alavi SA, Mueller WEG, Forouzanfar T, Helder MN. A systematic review on regenerative alveolar graft materials in clinical trials: Risk of bias and meta-analysis. J Plast Reconstr Aesthet Surg 2021; 75:356-365. [PMID: 34642060 DOI: 10.1016/j.bjps.2021.08.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 06/16/2021] [Accepted: 08/26/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Alveolar cleft grafting is a necessary procedure to restore bone defects. Randomized clinical trials (RCTs) are regarded as a golden standard for investigating the efficacy of treatments. Nevertheless, risk of bias (RoB) can still affect the validity of these trials. We aimed to conduct a systemic review of all control trials (CTs) using regenerative materials for alveolar cleft reconstructions to evaluate their RoB and perform a meta-analysis of new bone formation. METHODS Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE AND Google Scholar were searched up to October 2020. Thereafter, the articles underwent quality assessment (according to the Jadad scale and the Delphi list) for the evaluation of the RoB. RESULTS A total of 15 trials met the inclusion criteria, none of which reached a full score. Of these, 20% didn't randomize the trails, 73,33% failed to describe the way of randomization, and none reported the double-blinded criteria. Furthermore, allocation concealment (99.9%), intention to treat (100%), and patient awareness (100%) were inadequately described. The meta-analysis found no significant difference between regenerative materials and iliac crest graft. CONCLUSION This review showed high RoB in CTs implying quality improvement of CTs is necessary. Meta-analysis showed no significant difference between the regenerative materials and autogenous grafts.
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Affiliation(s)
- S A Alkaabi
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands; Department of Oral and Maxillofacial Surgery, Fujairah Hospital, Ministry of Health, United Arab Emirates.
| | - G A Alsabri
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands
| | - D S NatsirKalla
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands; Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - S A Alavi
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands
| | - W E G Mueller
- Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - T Forouzanfar
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands
| | - M N Helder
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands
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Comparison of Osteogenic Potentials of Dental Pulp and Bone Marrow Mesenchymal Stem Cells Using the New Cell Transplantation Platform, CellSaic, in a Rat Congenital Cleft-Jaw Model. Int J Mol Sci 2021; 22:ijms22179478. [PMID: 34502394 PMCID: PMC8430713 DOI: 10.3390/ijms22179478] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 08/27/2021] [Indexed: 12/18/2022] Open
Abstract
Scaffolds stimulate cell proliferation and differentiation and play major roles in providing growth and nutrition factors in the repair of bone defects. We used the recombinant peptide Cellnest™ to prepare the three-dimensional stem cell complex, CellSaic, and evaluated whether CellSaic containing rat dental pulp stem cells (rDPSCs) was better than that containing rat bone marrow stem cells (rBMSCs). rDPSC-CellSaic or rBMSC-CellSaic, cultured with or without osteogenic induction medium, formed the experimental and control groups, respectively. Osteoblast differentiation was evaluated in vitro and transplanted into a rat model with a congenital jaw fracture. Specimens were collected and evaluated by microradiology and histological analysis. In the experimental group, the amount of calcium deposits, expression levels of bone-related genes (RUNX2, ALP, BSP, and COL1), and volume of mineralized tissue, were significantly higher than those in the control group (p < 0.05). Both differentiated and undifferentiated rDPSC-CellSaic and only the differentiated rBMSC-CellSaic could induce the formation of new bone tissue. Overall, rBMSC-CellSaic and rDPSC-CellSaic made with Cellnest™ as a scaffold, provide excellent support for promoting bone regeneration in rat mandibular congenital defects. Additionally, rDPSC-CellSaic seems a better source for craniofacial bone defect repair than rBMSC-CellSaic, suggesting the possibility of using DPSCs in bone tissue regenerative therapy.
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30
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Latimer JM, Maekawa S, Yao Y, Wu DT, Chen M, Giannobile WV. Regenerative Medicine Technologies to Treat Dental, Oral, and Craniofacial Defects. Front Bioeng Biotechnol 2021; 9:704048. [PMID: 34422781 PMCID: PMC8378232 DOI: 10.3389/fbioe.2021.704048] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 06/29/2021] [Indexed: 01/10/2023] Open
Abstract
Additive manufacturing (AM) is the automated production of three-dimensional (3D) structures through successive layer-by-layer deposition of materials directed by computer-aided-design (CAD) software. While current clinical procedures that aim to reconstruct hard and soft tissue defects resulting from periodontal disease, congenital or acquired pathology, and maxillofacial trauma often utilize mass-produced biomaterials created for a variety of surgical indications, AM represents a paradigm shift in manufacturing at the individual patient level. Computer-aided systems employ algorithms to design customized, image-based scaffolds with high external shape complexity and spatial patterning of internal architecture guided by topology optimization. 3D bioprinting and surface modification techniques further enhance scaffold functionalization and osteogenic potential through the incorporation of viable cells, bioactive molecules, biomimetic materials and vectors for transgene expression within the layered architecture. These computational design features enable fabrication of tissue engineering constructs with highly tailored mechanical, structural, and biochemical properties for bone. This review examines key properties of scaffold design, bioresorbable bone scaffolds produced by AM processes, and clinical applications of these regenerative technologies. AM is transforming the field of personalized dental medicine and has great potential to improve regenerative outcomes in patient care.
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Affiliation(s)
- Jessica M Latimer
- Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, United States
| | - Shogo Maekawa
- Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, United States.,Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yao Yao
- Department of Periodontics & Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, United States.,Biointerfaces Institute, University of Michigan, Ann Arbor, MI, United States
| | - David T Wu
- Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, United States.,Laboratory for Cell and Tissue Engineering, Harvard John A. Paulson School of Engineering and Applied Sciences, Boston, MA, United States.,Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States
| | - Michael Chen
- Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, United States
| | - William V Giannobile
- Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, United States
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31
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Chen MH, Tai WC, Cheng NC, Chang CH, Chang PC. Characterization of the stemness and osteogenic potential of oral and sinus mucosal cells. J Formos Med Assoc 2021; 121:652-659. [PMID: 34233852 DOI: 10.1016/j.jfma.2021.06.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 06/10/2021] [Accepted: 06/17/2021] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/PURPOSE Covering the wounds from guided bone regeneration and sinus floor elevation with oral and sinus mucosa is a fundamental criterion for success. This study aimed to verify the regeneration capability of the mucosal connective tissue stromal cells by characterizing their stemness and osteogenic potentials. METHODS Bone marrow stromal cells (BMSCs), alveolar mucosa cells (AMCs), keratinized gingival cells (KGCs), and sinus mucosal cells (SMCs), were isolated from four Sprague-Dawley rats. The morphology and viability of the cells were investigated under a confocal microscope and by Alamar Blue. Stem cell surface markers were evaluated by flow cytometry. Expressions of pluripotent factors after initial seeding and an early osteogenic gene following 24 h of osteoinduction were evaluated by realtime PCR. Trilineage differentiation capability in long-term inductive cell culture was assessed by Alizarin Red, Alcian Blue, and Oil Red O staining. RESULTS BMSCs and AMCs were larger cells with smaller aspect ratios relative to KGCs and SMCs, and BMSCs revealed the greatest initial viability but the slowest proliferation. More than 94% of BMSCs, AMCs, and KGCs were double-positive for CD73 and CD90. Compared with BMSCs, AMCs expressed significantly higher Oct4 but reduced Cbfa1 after initial seeding, and AMCs and SMCs expressed significantly higher Cbfa1 following 24 h of osteoinduction. In long-term inductive cell culture, osteogenesis was observed in BMSCs, AMCs, and SMCs, chondrogenesis was observed in BMSCs, AMCs, and KGCs, and adipogenesis was evident in only BMSCs. CONCLUSION AMCs contain a high percentage of stem/progenitor cells and show differentiation capability toward osteogenic lineage.
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Affiliation(s)
- Ming-Hsu Chen
- Department of Otorhinolaryngology, Cathay General Hospital, Taipei, Taiwan
| | - Wei-Chiu Tai
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Nai-Chen Cheng
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Ching-He Chang
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
| | - Po-Chun Chang
- Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Division of Periodontics, Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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32
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Bicer M, Cottrell GS, Widera D. Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells. Stem Cell Res Ther 2021; 12:31. [PMID: 33413646 PMCID: PMC7791873 DOI: 10.1186/s13287-020-02094-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 12/10/2020] [Indexed: 12/17/2022] Open
Abstract
As populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the USA, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases of the bone, they are often associated with serious side effects including the development of oesophageal cancer, ocular inflammation, severe musculoskeletal pain and osteonecrosis of the jaw.The use of autologous mesenchymal stromal cells/mesenchymal stem cells (MSCs) is a possible alternative therapeutic approach to tackle osteoporosis while overcoming the limitations of traditional treatment options. However, osteoporosis can cause a decrease in the numbers of MSCs, induce their senescence and lower their osteogenic differentiation potential.Three-dimensional (3D) cell culture is an emerging technology that allows a more physiological expansion and differentiation of stem cells compared to cultivation on conventional flat systems.This review will discuss current understanding of the effects of different 3D cell culture systems on proliferation, viability and osteogenic differentiation, as well as on the immunomodulatory and anti-inflammatory potential of MSCs.
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Affiliation(s)
- Mesude Bicer
- Stem Cell Biology and Regenerative Medicine Group, Reading School of Pharmacy, University of Reading, PO Box 226, Whiteknights, Reading, RG6 6AP, UK
| | - Graeme S Cottrell
- Cellular and Molecular Neuroscience, School of Pharmacy, University of Reading, Reading, UK
| | - Darius Widera
- Stem Cell Biology and Regenerative Medicine Group, Reading School of Pharmacy, University of Reading, PO Box 226, Whiteknights, Reading, RG6 6AP, UK.
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33
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Galli M, Yao Y, Giannobile WV, Wang HL. Current and future trends in periodontal tissue engineering and bone regeneration. PLASTIC AND AESTHETIC RESEARCH 2021; 8. [PMID: 35765666 PMCID: PMC9236184 DOI: 10.20517/2347-9264.2020.176] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Periodontal tissue engineering involves a multi-disciplinary approach towards the regeneration of periodontal ligament, cementum and alveolar bone surrounding teeth, whereas bone regeneration specifically applies to ridge reconstruction in preparation for future implant placement, sinus floor augmentation and regeneration of peri-implant osseous defects. Successful periodontal regeneration is based on verifiable cementogenesis on the root surface, oblique insertion of periodontal ligament fibers and formation of new and vital supporting bone. Ultimately, regenerated periodontal and peri-implant support must be able to interface with surrounding host tissues in an integrated manner, withstand biomechanical forces resulting from mastication, and restore normal function and structure. Current regenerative approaches utilized in everyday clinical practice are mainly guided tissue/bone regeneration-based. Although these approaches have shown positive outcomes for small and medium-sized defects, predictability of clinical outcomes is heavily dependent on the defect morphology and clinical case selection. In many cases, it is still challenging to achieve predictable regenerative outcomes utilizing current approaches. Periodontal tissue engineering and bone regeneration (PTEBR) aims to improve the state of patient care by promoting reconstitution of damaged and lost tissues through the use of growth factors and signaling molecules, scaffolds, cells and gene therapy. The present narrative review discusses key advancements in PTEBR including current and future trends in preclinical and clinical research, as well as the potential for clinical translatability.
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Affiliation(s)
- Matthew Galli
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA
| | - Yao Yao
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA
| | - William V Giannobile
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.,Biointerfaces Institute, North Campus Research Complex, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.,Harvard School of Dental Medicine, Boston, MA 02115, USA
| | - Hom-Lay Wang
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA
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Arthur A, Gronthos S. Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue. Int J Mol Sci 2020; 21:E9759. [PMID: 33371306 PMCID: PMC7767389 DOI: 10.3390/ijms21249759] [Citation(s) in RCA: 158] [Impact Index Per Article: 31.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/14/2020] [Accepted: 12/16/2020] [Indexed: 12/13/2022] Open
Abstract
There has been an escalation in reports over the last decade examining the efficacy of bone marrow derived mesenchymal stem/stromal cells (BMSC) in bone tissue engineering and regenerative medicine-based applications. The multipotent differentiation potential, myelosupportive capacity, anti-inflammatory and immune-modulatory properties of BMSC underpins their versatile nature as therapeutic agents. This review addresses the current limitations and challenges of exogenous autologous and allogeneic BMSC based regenerative skeletal therapies in combination with bioactive molecules, cellular derivatives, genetic manipulation, biocompatible hydrogels, solid and composite scaffolds. The review highlights the current approaches and recent developments in utilizing endogenous BMSC activation or exogenous BMSC for the repair of long bone and vertebrae fractures due to osteoporosis or trauma. Current advances employing BMSC based therapies for bone regeneration of craniofacial defects is also discussed. Moreover, this review discusses the latest developments utilizing BMSC therapies in the preclinical and clinical settings, including the treatment of bone related diseases such as Osteogenesis Imperfecta.
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Affiliation(s)
- Agnieszka Arthur
- Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5001, Australia;
- Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5001, Australia
| | - Stan Gronthos
- Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5001, Australia;
- Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5001, Australia
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Liang W, Chen X, Dong Y, Zhou P, Xu F. Recent advances in biomaterials as instructive scaffolds for stem cells in tissue repair and regeneration. INT J POLYM MATER PO 2020. [DOI: 10.1080/00914037.2020.1848832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
- Wenqing Liang
- Department of Orthopaedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, P. R. China
| | - Xuerong Chen
- Department of Orthopaedics, Shaoxing People’s Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, P. R. China
| | - Yongqiang Dong
- Department of Orthopaedics, Xinchang People’s Hospital, Shaoxing, P. R. China
| | - Ping Zhou
- Department of Orthopaedics, Shaoxing People’s Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, P. R. China
| | - Fangming Xu
- Department of Orthopaedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, P. R. China
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Elangovan S, Gajendrareddy P, Ravindran S, Salem AK. Emerging local delivery strategies to enhance bone regeneration. ACTA ACUST UNITED AC 2020; 15:062001. [PMID: 32647095 PMCID: PMC10148649 DOI: 10.1088/1748-605x/aba446] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
In orthopedics and dentistry there is an increasing need for novel biomaterials and clinical strategies to achieve predictable bone regeneration. These novel molecular strategies have the potential to eliminate the limitations of currently available approaches. Specifically, they have the potential to reduce or eliminate the need to harvest autogenous bone, and the overall complexity of the clinical procedures. In this review, emerging tissue engineering strategies that have been, or are currently being, developed based on the current understanding of bone biology, development and wound healing will be discussed. In particular, protein/peptide based approaches, DNA/RNA therapeutics, cell therapy, and the use of exosomes will be briefly covered. The review ends with a summary of the current status of these approaches, their clinical translational potentials and their challenges.
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Affiliation(s)
- Satheesh Elangovan
- Department of Periodontics, The University of Iowa College of Dentistry, Iowa City, IA 52242, United States of America
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Kim MG, Park CH. Tooth-Supporting Hard Tissue Regeneration Using Biopolymeric Material Fabrication Strategies. Molecules 2020; 25:molecules25204802. [PMID: 33086674 PMCID: PMC7587995 DOI: 10.3390/molecules25204802] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 10/08/2020] [Accepted: 10/16/2020] [Indexed: 12/13/2022] Open
Abstract
The mineralized tissues (alveolar bone and cementum) are the major components of periodontal tissues and play a critical role to anchor periodontal ligament (PDL) to tooth-root surfaces. The integrated multiple tissues could generate biological or physiological responses to transmitted biomechanical forces by mastication or occlusion. However, due to periodontitis or traumatic injuries, affect destruction or progressive damage of periodontal hard tissues including PDL could be affected and consequently lead to tooth loss. Conventional tissue engineering approaches have been developed to regenerate or repair periodontium but, engineered periodontal tissue formation is still challenging because there are still limitations to control spatial compartmentalization for individual tissues and provide optimal 3D constructs for tooth-supporting tissue regeneration and maturation. Here, we present the recently developed strategies to induce osteogenesis and cementogenesis by the fabrication of 3D architectures or the chemical modifications of biopolymeric materials. These techniques in tooth-supporting hard tissue engineering are highly promising to promote the periodontal regeneration and advance the interfacial tissue formation for tissue integrations of PDL fibrous connective tissue bundles (alveolar bone-to-PDL or PDL-to-cementum) for functioning restorations of the periodontal complex.
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Affiliation(s)
- Min Guk Kim
- Department of Dental Science, Graduate School, Kyungpook National University, Daegu 41940, Korea;
- Department of Dental Biomaterials, School of Dentistry, Kyungpook National University, Daegu 41940, Korea
| | - Chan Ho Park
- Department of Dental Science, Graduate School, Kyungpook National University, Daegu 41940, Korea;
- Department of Dental Biomaterials, School of Dentistry, Kyungpook National University, Daegu 41940, Korea
- Institute for Biomaterials Research and Development, Kyungpook National University, Daegu 41940, Korea
- Correspondence: ; Tel.: +82-53-660-6890
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Bakopoulou A. Prospects of Advanced Therapy Medicinal Products-Based Therapies in Regenerative Dentistry: Current Status, Comparison with Global Trends in Medicine, and Future Perspectives. J Endod 2020; 46:S175-S188. [PMID: 32950189 DOI: 10.1016/j.joen.2020.06.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
INTRODUCTION Regenerative medicine offers innovative approaches to restore damaged tissues on the basis of tissue engineering (TE). Although research on advanced therapy medicinal products (ATMPs) has been very active in recent years, the number of licensed products remains surprisingly low and restricted to the treatment of severe, incurable diseases. METHODS This paper provides a critical review of current literature on the regulatory, clinical, and commercial status of ATMP-based therapies in the EU and worldwide and the hurdles to overcome for their broader application in Regenerative Dentistry. RESULTS Competent authorities have focused on developing regulatory pathways to address unmet patient needs. Oncology represents the dominating field, followed by cardiovascular, musculoskeletal, neurodegenerative, immunologic, and inherited diseases. Yet, the status remains in early development, and scientific, regulatory, and cost-effectiveness issues impose considerable hurdles toward marketing authorization, technology adoption, and patient accessibility. In this context, although regenerative dentistry has achieved breakthrough innovations in TE of several dental/oral tissues in preclinical models, it has hardly harnessed research progress to integrate innovative regenerative treatments into clinical practice. CONCLUSION Global demographic changes, which demonstrate a steady increase of the aging population, highlight the societal need for the application of ATMP-based therapies in the treatment of noncommunicable diseases (NCDs). Although oral diseases, as an integral part of NCDs, are not life-threatening and largely preventable, they sustain high prevalence, with severe burden on economy and quality of life. In this perspective, the urgent request to ultimately translate draining research in dental TE conducted during the last decades into innovative treatments brought safely and cost-effectively into society at large still holds the stage. This review provides an overview of the regulatory, clinical, and commercial status of ATMP-based therapies in the European Union and worldwide and the hurdles to overcome for their broader application in regenerative dentistry.
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Affiliation(s)
- Athina Bakopoulou
- Faculty of Health Sciences, Department of Prosthodontics, School of Dentistry, Aristotle University of Thessaloniki (AUTH), Thessaloniki, Greece.
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Varshney S, Dwivedi A, Pandey V. Efficacy of autologous stem cells for bone regeneration during endosseous dental implants insertion - A systematic review of human studies. J Oral Biol Craniofac Res 2020; 10:347-355. [PMID: 32714787 DOI: 10.1016/j.jobcr.2020.06.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 06/21/2020] [Indexed: 12/11/2022] Open
Abstract
Availability of adequate quantity and quality of bone is prerequisite for longevity and survival of endosseous dental implants. Most of the clinicians face with the problem of lack of bone due to long-standing edentulism during this treatment modality. Conventional therapies with the use of various types of bone grafts and membranes have provided clinicians with unpredictable and compromised results. Cell-based therapies utilizing undifferentiated cells, that have the potential to differentiate into various cell types including osteoblastic lineages, have demonstrated through various previously conducted in-vitro and animal studies, a successful formation of bone in a predictable manner. Thus the main objective of this review was to evaluate the effectiveness of these therapies when applied on human subjects. A search was carried out in MEDLINE (via PubMed) and Cochrane CENTRAL databases for completed randomized and non-randomised clinical trials utilizing stem cell-based therapies with histologic and radiographic analysis written in English up to January 2019. This search of the literature yielded 10 studies meeting the inclusion and exclusion criteria. In all these studies, stem cells were primarily used to achieve bone augmentation during insertion of endosseous dental implants. Results of these therapies conducted on human subjects have shown a positive impact on bone regeneration, in particular, therapies utilizing bone marrow and adipose tissue derived stem cells. But the clinicians need to examine the efficacy, safety, feasibility of these therapies while treating large size defects or planning for shorter healing period and early loading of dental implants.
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Affiliation(s)
- Shailesh Varshney
- Department of Periodontology, School of Dental Sciences, Sharda University, Greater Noida, Uttar Pradesh, India
| | - Anshuman Dwivedi
- Adv Dip in Stem Cells and Regenerative Medicine (Boston), V 67, Sector 12, Noida, Uttar Pradesh, India
| | - Vibha Pandey
- Noida Psychiatry Centre, P 5, Sector 12, Noida, Uttar Pradesh, India
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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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Wang X, Ao J, Lu H, Zhao Q, Ma Y, Zhang J, Ren H, Zhang Y. Osteoimmune Modulation and Guided Osteogenesis Promoted by Barrier Membranes Incorporated with S-Nitrosoglutathione (GSNO) and Mesenchymal Stem Cell-Derived Exosomes. Int J Nanomedicine 2020; 15:3483-3496. [PMID: 32523344 PMCID: PMC7237116 DOI: 10.2147/ijn.s248741] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 05/05/2020] [Indexed: 12/11/2022] Open
Abstract
Background The use of polycaprolactone (PCL) for bone defects in a clinical setting is limited due to a lack of bioactivity. Exosomes derived from mesenchymal stem cells (MSCs) have an important immunoregulatory potential and together with S-nitrosoglutathione (GSNO) they possess therapeutic potential for bone regeneration. Materials and Methods In this study, PCL was modified with GSNO and MSC-derived exosomes and the impact on macrophages and osteogenes is evaluated. Results MSC-derived exosomes exhibited a cup-shaped morphology and were internalized by macrophages and human bone marrow-derived mesenchymal stromal cells (hBMSCs). The pattern of internalization of scaffold-immobilized exosomes was similar in RAW264.7 cells and hBMSCs after 4h and 24h of co-culture. Assessment of macrophage morphology under inflammatory conditions by scanning electronic microscopy (SEM) and confocal microscopy demonstrated macrophages were significantly elongated and expression of pro-inflammatory genes markedly decreased when co-cultured with PCL/PDA + GSNO + exosome scaffolds. Furthermore, this scaffold modification significantly enhanced osteogenic differentiation of hBMSCs. Discussion This study demonstrated the possibility of using a GSNO- and exosome-based strategy to adapt barrier membrane scaffolds. PCL/PDA + GSNO + exosome scaffolds may serve as an important barrier membrane for osteogenesis and tissue regeneration.
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Affiliation(s)
- Xin Wang
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, People's Republic of China.,Joint Orthopaedic Research Center of Zunyi Medical University & University of Rochester Medical Center (JCMR-ZMU & URMC), Zunyi Medical University, Zunyi 563000, Guizhou, People's Republic of China
| | - Jun Ao
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, People's Republic of China
| | - Haiping Lu
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, People's Republic of China
| | - Qingyu Zhao
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, People's Republic of China
| | - Yaping Ma
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, People's Republic of China.,Joint Orthopaedic Research Center of Zunyi Medical University & University of Rochester Medical Center (JCMR-ZMU & URMC), Zunyi Medical University, Zunyi 563000, Guizhou, People's Republic of China
| | - Jun Zhang
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, People's Republic of China
| | - Hao Ren
- Shenzhen Institute for Innovation and Translational Medicine, Shenzhen International Biological Valley-Life Science Industrial Park, Shenzhen, Guangdong 518119, People's Republic of China
| | - Yi Zhang
- Joint Orthopaedic Research Center of Zunyi Medical University & University of Rochester Medical Center (JCMR-ZMU & URMC), Zunyi Medical University, Zunyi 563000, Guizhou, People's Republic of China.,Department of Hygiene Toxicology, School of Public Health, Zunyi Medical University, Zunyi 563000, Guizhou, People's Republic of China
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Functional Validation of a New Alginate-based Hydrogel Scaffold Combined with Mesenchymal Stem Cells in a Rat Hard Palate Cleft Model. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2020; 8:e2743. [PMID: 32440413 PMCID: PMC7209877 DOI: 10.1097/gox.0000000000002743] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 02/05/2020] [Indexed: 12/27/2022]
Abstract
Background: One of the major difficulties in cleft palate repair is the requirement for several surgical procedures and autologous bone grafting to form a bony bridge across the cleft defect. Engineered tissue, composed of a biomaterial scaffold and multipotent stem cells, may be a useful alternative for minimizing the non-negligible risk of donor site morbidity. The present study was designed to confirm the healing and osteogenic properties of a novel alginate-based hydrogel in palate repair. Methods: Matrix constructs, seeded with allogeneic bone marrow–derived mesenchymal stem cells (BM-MSCs) or not, were incorporated into a surgically created, critical-sized cleft palate defect in the rat. Control with no scaffold was also tested. Bone formation was assessed using microcomputed tomography at weeks 2, 4, 8, and 12 and a histologic analysis at week 12. Results: At 12 weeks, the proportion of bone filling associated with the use of hydrogel scaffold alone did not differ significantly from the values observed in the scaffold-free experiment (61.01% ± 5.288% versus 36.91% ± 5.132%; p = 0.1620). The addition of BM-MSCs stimulated bone formation not only at the margin of the defect but also in the center of the implant. Conclusions: In a relevant in vivo model of cleft palate in the rat, we confirmed the alginate-based hydrogel’s biocompatibility and real advantages for tissue healing. Addition of BM-MSCs stimulated bone formation in the center of the implant, demonstrating the new biomaterial’s potential for use as a bone substitute grafting material for cleft palate repair.
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Seetharaman R, Mahmood A, Kshatriya P, Patel D, Srivastava A. An Overview on Stem Cells in Tissue Regeneration. Curr Pharm Des 2020; 25:2086-2098. [PMID: 31298159 DOI: 10.2174/1381612825666190705211705] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 06/19/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Deteriorations in tissues and decline in organ functions, due to chronic diseases or with advancing age or sometimes due to infections or injuries, can severely compromise the quality of life of an individual. Regenerative medicine, a field of medical research focuses on replacing non-functional or dead cells or repairing or regenerating tissues and organs to restore normal functions of an impaired organ. Approaches used in regenerative therapy for achieving the objective employ a number of means which include soluble biomolecules, stem cell transplants, tissue engineering, gene therapy and reprogramming of cells according to target tissue types. Stem cells transplant and tissue regeneration methods for treating various diseases have rapidly grown in usage over the past decades or so. There are different types of stem cells such as mesenchymal, hematopoietic, embryonic, mammary, intestinal, endothelial, neural, olfactory, neural crest, testicular and induced pluripotent stem cells. METHODS This review covers the recent advances in tissue regeneration and highlights the application of stem cell transplants in treating many life-threatening diseases or in improving quality of life. RESULTS Remarkable progress in stem cell research has established that the cell-based therapy could be an option for treating diseases which could not be cured by conventional medical means till recent. Stem cells play major roles in regenerative medicine with its exceptional characteristics of self-renewal capacity and potential to differentiate into almost all types of cells of a body. CONCLUSION Vast number of reports on preclinical and clinical application of stem cells revealed its vital role in disease management and many pharmacological industries around the globe working to achieve effective stem cell based products.
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Affiliation(s)
| | | | | | | | - Anand Srivastava
- Global Institute of Stem Cell Therapy and Research, 4660 La Jolla Village Drive, San Diego, CA 92122, United States
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Miller MQ, McColl LF, Arul MR, Nip J, Madhu V, Beck G, Mathur K, Sahadeo V, Kerrigan JR, Park SS, Christophel JJ, Dighe AS, Kumbar SG, Cui Q. Assessment of Hedgehog Signaling Pathway Activation for Craniofacial Bone Regeneration in a Critical-Sized Rat Mandibular Defect. JAMA FACIAL PLAST SU 2020; 21:110-117. [PMID: 30520953 DOI: 10.1001/jamafacial.2018.1508] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Importance Osseous craniofacial defects are currently reconstructed with bone grafting, rigid fixation, free tissue transfer, and/or recombinant human bone morphogenetic protein 2. Although these treatment options often have good outcomes, they are associated with substantial morbidity, and many patients are not candidates for free tissue transfer. Objective To assess whether polysaccharide-based scaffold (PS) constructs that are cross-linked with smoothened agonist (SAG), vascular endothelial growth factor (VEGF), and bone morphogenetic protein 6 (BMP-6) would substantially increase bone regeneration. Design, Setting, and Participants This animal model study was conducted at the University of Virginia School of Medicine Cui Laboratory from March 1, 2017, to June 30, 2017. Thirty-three 10-week-old female Lewis rats were acquired for the study. Bilateral nonsegmental critical-sized defects were created in the angle of rat mandibles. The defects were either left untreated or filled with 1 of the 9 PSs. The rats were killed after 8 weeks, and bone regeneration was evaluated using microcomputed tomographic imaging and mechanical testing. Analysis of variance testing was used to compare the treatment groups. Main Outcomes and Measures Blinded analysis and computer analysis of the microcomputed tomographic images were used to assess bone regeneration. Results In the 33 female Lewis rats, minimal healing was observed in the untreated mandibles. Addition of SAG was associated with increases in bone regeneration and bone density in all treatment groups, and maximum bone healing was seen in the group with BMP-6, VEGF, and SAG cross-linked to PS. For each of the 5 no scaffold group vs BMP-6, VEGF, and SAG cross-linked to PS group comparisons, mean defect bone regeneration was 4.14% (95% CI, 0.94%-7.33%) vs 66.19% (95% CI, 54.47%-77.90%); mean bone volume, 14.52 mm3 (95% CI, 13.07-15.97 mm3) vs 20.87 mm3 (95% CI, 14.73- 27.01 mm3); mean bone surface, 68.97 mm2 (95% CI, 60.08-77.85 mm2) vs 96.77 mm2 (95% CI, 76.11-117.43 mm2); mean ratio of bone volume to total volume, 0.11 (95% CI, 0.10-0.11) vs 0.15 (95% CI, 0.10-0.19); and mean connectivity density 0.03 (95% CI, 0.02-0.05) vs 0.32 (95% CI, 0.25-0.38). On mechanical testing, mandibles with untreated defects broke with less force than control mandibles in which no defect was made, although this force did not reach statistical significance. No significant difference in force to fracture was observed among the treatment groups. Conclusions and Relevance In this rat model study, activation of the hedgehog signaling pathway using smoothened agonist was associated with increased craniofacial bone regeneration compared with growth factors alone, including US Food and Drug Administration-approved recombinant human bone morphogenetic protein 2. Pharmaceuticals that target this pathway may offer a new reconstructive option for bony craniofacial defects as well as nonunion and delayed healing fractures. Level of Evidence NA.
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Affiliation(s)
- Matthew Q Miller
- Department of Orthopaedic Surgery, University of Virginia, Charlottesville.,Department of Otolaryngology, University of Virginia, Charlottesville
| | - Logan F McColl
- Department of Orthopaedic Surgery, University of Virginia, Charlottesville.,Department of Otolaryngology, University of Virginia, Charlottesville
| | - Michael R Arul
- Department of Orthopaedic Surgery, University of Connecticut, Farmington
| | - Jonathan Nip
- Department of Orthopaedic Surgery, University of Connecticut, Farmington.,Department of Biomedical Engineering, University of Connecticut, Farmington.,Department of Materials Science and Engineering, University of Connecticut, Farmington
| | - Vedavathi Madhu
- Department of Orthopaedic Surgery, University of Virginia, Charlottesville
| | - Gina Beck
- Department of Orthopaedic Surgery, University of Virginia, Charlottesville
| | - Kishan Mathur
- Center for Applied Biomechanics, Department of Mechanical and Aerospace Engineering, University of Virginia, Charlottesville
| | - Vashaana Sahadeo
- Department of Orthopaedic Surgery, University of Virginia, Charlottesville
| | - Jason R Kerrigan
- Department of Orthopaedic Surgery, University of Virginia, Charlottesville.,Center for Applied Biomechanics, Department of Mechanical and Aerospace Engineering, University of Virginia, Charlottesville
| | - Stephen S Park
- Department of Otolaryngology, University of Virginia, Charlottesville
| | | | - Abhijit S Dighe
- Department of Orthopaedic Surgery, University of Virginia, Charlottesville
| | - Sangamesh G Kumbar
- Department of Orthopaedic Surgery, University of Connecticut, Farmington.,Department of Biomedical Engineering, University of Connecticut, Farmington.,Department of Materials Science and Engineering, University of Connecticut, Farmington
| | - Quanjun Cui
- Department of Orthopaedic Surgery, University of Virginia, Charlottesville
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Shi L, Tee BC, Cotter L, Sun Z. Enhance Mandibular Symphyseal Surface Bone Growth with Autologous Mesenchymal Stem Cell Sheets: An Animal Study. Aesthetic Plast Surg 2020; 44:191-200. [PMID: 31701201 DOI: 10.1007/s00266-019-01494-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 08/31/2019] [Indexed: 10/25/2022]
Abstract
INTRODUCTION The size and shape of the chin strongly influence facial profile and harmony. The current correction of chin deficiency mostly relies on genioplasty surgery involving osteotomy. To avoid osteotomy, one possible alternative is to enhance bone growth at the mental protuberance area with cell sheet transplantation. This study was undertaken to evaluate the efficacy of this approach in a pig model. MATERIALS AND METHODS Five 4-month-old pigs were included for mandibular bone marrow aspiration and MSC isolation. Triple-layer MSC sheets were then fabricated and utilized using culture-expanded MSCs. Four weeks after bone marrow aspiration, subperiosteal pockets were created on the labial symphyseal surface, followed by transplantation of autogenous MSC sheets to one randomly chosen side with the other side (control) receiving no transplantation. Six weeks after the surgery, the pigs were euthanized and the specimens from both sides were collected for computed tomography (CT) and histological and immunohistochemical analysis. Measurements between the experimental and control sides were compared using paired t tests. RESULTS MSC sheet fabrication and transplantation were reliably conducted. The labial cortical bone thickness increased significantly with MSC sheet transplantation by an average of 2 mm (p = 0.0001). The average measurements of mineral apposition rate and cell proliferation at the cell sheet side tended to be higher than the control side although the differences did not reach statistical significance (p = 0.1-0.2). Tissue mineral density measurements from CT images and bone volume fraction (BV/TV) measurements from histologic images were identical between the two sides (p > 0.5). CONCLUSION These data provide a proof of concept that autologous MSC sheets may be transplanted to the subperiosteal region of the mandibular symphysis to stimulate local surface bone growth. NO LEVEL ASSIGNED This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Xing F, Duan X, Liu M, Chen J, Long C, Chen R, Sun J, Wu S, Chen L, Xiang Z. [Construction and preliminary study on biological characteristics of composite cell sheets of mesenchymal stem cells and endothelial progenitor cells derived from peripheral blood]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2020; 34:109-115. [PMID: 31939245 DOI: 10.7507/1002-1892.201901087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Objective To separate peripheral blood mesenchymal stem cells (PBMSC) and peripheral blood endothelial progenitor cells (PBEPC) from peripheral blood, and investigate the biological characteristics of composite cell sheets of PBMSC and PBEPC. Methods The peripheral blood of healthy adult New Zealand white rabbits was extracted and PBMSC and PBEPC were separated by density gradient centrifugation. Morphological observation and identification of PBMSC and PBEPC were performed. The 3rd generation of PBMSC and PBEPC were used to construct a composite cell sheet at a ratio of 1∶1, and the 3rd generation of PBMSC was used to construct a single cell sheet as control. The distributions of cells in two kinds of cell sheets were observed by HE staining. In addition, the expression of alkaline phosphatase (ALP), osteocalcin (OCN), and vascular endothelial growth factor (VEGF) in the supernatants of cell sheets were observed by ELISA at 1, 5, and 10 days after osteogenic induction. Results The morphology of PBMSC was spindle-shaped or polygonal, and PBMSC had good abilities of osteogenic and adipogenic differentiation. The morphology of PBEPC was paved stone-like, and the tube-forming test of PBEPC was positive. Two kinds of cell sheets were white translucent. The results of HE staining showed that the composite cell sheet had more cell layers and higher cell density than the single cell sheet. The expressions of ALP, OCN, and VEGF in the supernatant of the two groups of cell sheets increased with the time of induction. The expression of OCN in the group of composite cell sheet was significantly higher than that in the group of single cell sheet on the 5th and 10th day, ALP on the 10th day was significantly higher than that in the group of single cell sheet, VEGF expression on the 1st, 5th, and 10th day was significantly higher than that in the group of single cell sheet, all showing significant differences ( P<0.05), and there was no significant difference between the two groups at other time points ( P>0.05). Conclusion PBMSC have stable differentiation ability, and they have good application prospects because of their minimally invasive access. Composite cell membranes constructed by co-culture of two kinds of cells and induction of membrane formation provides a new idea and exploration for tissue defect repair.
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Affiliation(s)
- Fei Xing
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Xin Duan
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Ming Liu
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Jialei Chen
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Cheng Long
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Ran Chen
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Jiachen Sun
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Shuang Wu
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Li Chen
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Zhou Xiang
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041,
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Wang N, Liu X, Shi L, Liu Y, Guo S, Liu W, Li X, Meng J, Ma X, Guo Z. Identification of a prolonged action molecular GLP-1R agonist for the treatment of femoral defects. Biomater Sci 2020; 8:1604-1614. [PMID: 31967113 DOI: 10.1039/c9bm01426h] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Poly-GLP-1 promotes angiogenesis to accelerate bone formationviaBMSC differentiation and M2 polarization.
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Bone Tissue Regeneration in the Oral and Maxillofacial Region: A Review on the Application of Stem Cells and New Strategies to Improve Vascularization. Stem Cells Int 2019; 2019:6279721. [PMID: 32082383 PMCID: PMC7012224 DOI: 10.1155/2019/6279721] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 12/13/2019] [Indexed: 02/07/2023] Open
Abstract
Bone tissue engineering techniques are a promising alternative for the use of autologous bone grafts to reconstruct bone defects in the oral and maxillofacial region. However, for successful bone regeneration, adequate vascularization is a prerequisite. This review presents and discusses the application of stem cells and new strategies to improve vascularization, which may lead to feasible clinical applications. Multiple sources of stem cells have been investigated for bone tissue engineering. The stromal vascular fraction (SVF) of human adipose tissue is considered a promising single source for a heterogeneous population of essential cells with, amongst others, osteogenic and angiogenic potential. Enhanced vascularization of tissue-engineered grafts can be achieved by different mechanisms: vascular ingrowth directed from the surrounding host tissue to the implanted graft, vice versa, or concomitantly. Vascular ingrowth into the implanted graft can be enhanced by (i) optimizing the material properties of scaffolds and (ii) their bioactivation by incorporation of growth factors or cell seeding. Vascular ingrowth directed from the implanted graft towards the host tissue can be achieved by incorporating the graft with either (i) preformed microvascular networks or (ii) microvascular fragments (MF). The latter may have stimulating actions on both vascular ingrowth and outgrowth, since they contain angiogenic stem cells like SVF, as well as vascularized matrix fragments. Both adipose tissue-derived SVF and MF are cell sources with clinical feasibility due to their large quantities that can be harvested and applied in a one-step surgical procedure. During the past years, important advancements of stem cell application and vascularization in bone tissue regeneration have been made. The development of engineered in vitro 3D models mimicking the bone defect environment would facilitate new strategies in bone tissue engineering. Successful clinical application requires innovative future investigations enhancing vascularization.
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Characterization of progenitor/stem cell population from human dental socket and their multidifferentiation potential. Cell Tissue Bank 2019; 21:31-46. [PMID: 31807957 DOI: 10.1007/s10561-019-09794-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 11/23/2019] [Indexed: 02/06/2023]
Abstract
Dental stem cells have many applications in medicine, dentistry and stem cell biology in general due to their easy accessibility and low morbidity. A common surgical manoeuvre after a tooth extraction is the dental socket curettage which is necessary to clean the alveolus and favour alveolar bone healing. This procedure can cause very low morbidity compared to bone marrow collection procedures and the collected material is normally discarded. In order to investigate if the tissue obtained by dental socket curettage after a tooth extraction was a feasible alternative source to isolate human stem cells, we isolated and characterized two different stem cell populations based on STRO-1 and CD146 expression. We were able to collect and grow cells from dental socket of vital and non-vital teeth. Both populations were proliferative, clonogenic and expressed STRO-1, CD146, CD90, NG2, PDGFR-β, which are markers found in stem cells, presented in vitro multiline-differentiation into osteogenic, chondrogenic, and adipogenic tissue, and in vivo transplanted cells formed mineralized tissue. Interestingly, STRO-1+ clonogenic cells presented better multidifferentiation than CD146+ cells. Our results showed that mesenchymal stem cells can be isolated from the tiny tissue collected by dental socket curettage after vital and non-vital tooth extraction and suggest that STRO-1 is an important marker to be used to sort cells with multidifferentiation capacity.
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Cabrera-Pérez R, Monguió-Tortajada M, Gámez-Valero A, Rojas-Márquez R, Borràs FE, Roura S, Vives J. Osteogenic commitment of Wharton's jelly mesenchymal stromal cells: mechanisms and implications for bioprocess development and clinical application. Stem Cell Res Ther 2019; 10:356. [PMID: 31779673 PMCID: PMC6883559 DOI: 10.1186/s13287-019-1450-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 10/03/2019] [Accepted: 10/11/2019] [Indexed: 12/12/2022] Open
Abstract
Background Orthopaedic diseases are one of the major targets for regenerative medicine. In this context, Wharton’s jelly (WJ) is an alternative source to bone marrow (BM) for allogeneic transplantation since its isolation does not require an invasive procedure for cell collection and does not raise major ethical concerns. However, the osteogenic capacity of human WJ-derived multipotent mesenchymal stromal cells (MSC) remains unclear. Methods Here, we compared the baseline osteogenic potential of MSC from WJ and BM cell sources by cytological staining, quantitative real-time PCR and proteomic analysis, and assessed chemical and biological strategies for priming undifferentiated WJ-MSC. Concretely, different inhibitors/activators of the TGFβ1-BMP2 signalling pathway as well as the secretome of differentiating BM-MSC were tested. Results Cytochemical staining as well as gene expression and proteomic analysis revealed that osteogenic commitment was poor in WJ-MSC. However, stimulation of the BMP2 pathway with BMP2 plus tanshinone IIA and the addition of extracellular vesicles or protein-enriched preparations from differentiating BM-MSC enhanced WJ-MSC osteogenesis. Furthermore, greater outcome was obtained with the use of conditioned media from differentiating BM-MSC. Conclusions Altogether, our results point to the use of master banks of WJ-MSC as a valuable alternative to BM-MSC for orthopaedic conditions.
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Affiliation(s)
- Raquel Cabrera-Pérez
- Cell Therapy Service, Blood and Tissue Bank (BST), Barcelona, Catalonia, Spain. .,Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Catalonia, Spain.
| | - Marta Monguió-Tortajada
- REMAR-IVECAT Group, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Catalonia, Spain
| | - Ana Gámez-Valero
- REMAR-IVECAT Group, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Catalonia, Spain
| | - Raquel Rojas-Márquez
- Cell Therapy Service, Blood and Tissue Bank (BST), Barcelona, Catalonia, Spain.,Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Barcelona, Catalonia, Spain
| | - Francesc Enric Borràs
- REMAR-IVECAT Group, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Catalonia, Spain.,Nephrology Service, Germans Trias i Pujol University Hospital, Badalona, Catalonia, Spain
| | - Santiago Roura
- ICREC Research Program, Health Science Research Institute Germans Trias i Pujol (IGTP), Badalona, Catalonia, Spain
| | - Joaquim Vives
- Cell Therapy Service, Blood and Tissue Bank (BST), Barcelona, Catalonia, Spain. .,Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona (UAB), Barcelona, Catalonia, Spain. .,Medicine Department, Universitat Autònoma de Barcelona (UAB), Badalona, Catalonia, Spain.
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