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Cosmo LAM, Coutinho RM, de Macedo LGS, Aloise AC, Jayme SJ, Zeferino JPG, Graziano A, Martinez EF, Moy PK, Pelegrine AA. Use of autologous micrografts associated with xenogeneic anorganic bone in vertical bone augmentation procedures with Barbell Technique®. Clin Implant Dent Relat Res 2024; 26:1289-1302. [PMID: 39302718 DOI: 10.1111/cid.13387] [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: 03/15/2024] [Revised: 08/22/2024] [Accepted: 08/24/2024] [Indexed: 09/22/2024]
Abstract
INTRODUCTION Bidirectional vertical ridge augmentation in the posterior maxilla is very challenging. PURPOSE To evaluate the regenerative potential of micrografts, derived from periosteum or bone tissue, added to an anorganic xenograft in vertical reconstruction of the posterior maxilla, by a prospective, controlled study. MATERIALS AND METHODS After clinical selection and the analysis of CBCT scans, 24 posterior maxillary sites, in 19 patients, were treated by using Barbell Technique®. Sites requiring both inlay and onlay reconstruction were enrolled in the study. In the Control Group (CG, n = 8), a xenograft was used in the inlay site and for the onlay site, a 1:1 mix of xenograft and an autograft was used. In Test Group 1 (TG1, n = 8), both inlay and onlay sites were grafted with the xenograft associated with the micrografts derived from periosteum. In Test Group 2 (TG2, n = 8), both inlay and onlay sites were grafted with the xenograft associated with the micrografts derived from bone. Six months after the procedures, CBCT scans were obtained, and bone biopsy samples were harvested during implant placement surgery. The bone specimens were analyzed histomorphometrically, by measuring the percentages of vital mineralized tissue (VMT), non vital mineralized tissue (NVMT) and non mineralized tissue (NMT). Immunohistochemically, the levels of VEGF were categorized by a score approach. RESULTS Histomorphometric analysis revealed, for the inlay grafts, no significant difference among the groups for VMT, NVMT and NMT. However, for onlay grafts, CG achieved a higher amount of VMT in comparison with TG2, and the opposite occurred for NMT values. In this regard, no statistical difference was observed between CG and TG1. Concerning immunohistochemistry, the VEGF values for CG and TG1 were slightly higher than those obtained by TG2 for both inlay and onlay grafts, but without statistical significance. CBCT analysis showed a similar level of gain for all groups, for both inlay and onlay bone augmentation sites. Clinically, one implant (in CG) within a total of 50 implants installed, had early failure and was replaced after 3 months. All patients received implant supported prosthesis. CONCLUSION This study indicated that the clinical use of micrograft derived from periosteum may have some potential to increase bone formation in onlay reconstructions, unlike the micrograft derived from bone tissue.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Peter Karyen Moy
- Dental Implant Center, University of California, Los Angeles, California, USA
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Patntirapong S, Khankhow J, Julamorn S. Long-term passage impacts human dental pulp stem cell activities and cell response to drug addition in vitro. PeerJ 2024; 12:e17913. [PMID: 39193517 PMCID: PMC11348901 DOI: 10.7717/peerj.17913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 07/23/2024] [Indexed: 08/29/2024] Open
Abstract
Background Dental pulp stem cells (DPSCs) possess mesenchymal stem cell characteristics and have potential for cell-based therapy. Cell expansion is essential to achieve sufficient cell numbers. However, continuous cell replication causes cell aging in vitro, which usually accompanies and potentially affect DPSC characteristics and activities. Continuous passaging could alter susceptibility to external factors such as drug treatment. Therefore, this study sought to investigate potential outcome of in vitro passaging on DPSC morphology and activities in the absence or presence of external factor. Methods Human DPSCs were subcultured until reaching early passages (P5), extended passages (P10), and late passages (P15). Cells were evaluated and compared for cell and nuclear morphologies, cell adhesion, proliferative capacity, alkaline phosphatase (ALP) activity, and gene expressions in the absence or presence of external factor. Alendronate (ALN) drug treatment was used as an external factor. Results Continuous passaging of DPSCs gradually lost their normal spindle shape and increased in cell and nuclear sizes. DPSCs were vulnerable to ALN. The size and shape were altered, leading to morphological abnormality and inhomogeneity. Long-term culture and ALN interfered with cell adhesion. DPSCs were able to proliferate irrespective of cell passages but the rate of cell proliferation in late passages was slower. ALN at moderate dose inhibited cell growth. ALN caused reduction of ALP activity in early passage. In contrast, extended passage responded differently to ALN by increasing ALP activity. Late passage showed higher collagen but lower osteocalcin gene expressions compared with early passage in the presence of ALN. Conclusion An increase in passage number played critical role in cell morphology and activities as well as responses to the addition of an external factor. The effects of cell passage should be considered when used in basic science research and clinical applications.
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Affiliation(s)
- Somying Patntirapong
- Thammasat University Research Unit in Dental and Bone Substitute Biomaterials, Faculty of Dentistry, Thammasat University, Pathumthani, Thailand
| | | | - Sikarin Julamorn
- Faculty of Dentistry, Thammasat University, Pathumthani, Thailand
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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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Bai X, Cao R, Wu D, Zhang H, Yang F, Wang L. Dental Pulp Stem Cells for Bone Tissue Engineering: A Literature Review. Stem Cells Int 2023; 2023:7357179. [PMID: 37868704 PMCID: PMC10586346 DOI: 10.1155/2023/7357179] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 06/03/2023] [Accepted: 09/19/2023] [Indexed: 10/24/2023] Open
Abstract
Bone tissue engineering (BTE) is a promising approach for repairing and regenerating damaged bone tissue, using stem cells and scaffold structures. Among various stem cell sources, dental pulp stem cells (DPSCs) have emerged as a potential candidate due to their multipotential capabilities, ability to undergo osteogenic differentiation, low immunogenicity, and ease of isolation. This article reviews the biological characteristics of DPSCs, their potential for BTE, and the underlying transcription factors and signaling pathways involved in osteogenic differentiation; it also highlights the application of DPSCs in inducing scaffold tissues for bone regeneration and summarizes animal and clinical studies conducted in this field. This review demonstrates the potential of DPSC-based BTE for effective bone repair and regeneration, with implications for clinical translation.
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Affiliation(s)
- Xiaolei Bai
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Ruijue Cao
- Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Danni Wu
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Huicong Zhang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Fan Yang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
| | - Linhong Wang
- Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310018, Zhejiang, China
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Alarcón-Apablaza J, Prieto R, Rojas M, Fuentes R. Potential of Oral Cavity Stem Cells for Bone Regeneration: A Scoping Review. Cells 2023; 12:1392. [PMID: 37408226 PMCID: PMC10216382 DOI: 10.3390/cells12101392] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/30/2023] [Accepted: 05/04/2023] [Indexed: 07/07/2023] Open
Abstract
Bone loss is a common problem that ranges from small defects to large defects after trauma, surgery, or congenital malformations. The oral cavity is a rich source of mesenchymal stromal cells (MSCs). Researchers have documented their isolation and studied their osteogenic potential. Therefore, the objective of this review was to analyze and compare the potential of MSCs from the oral cavity for use in bone regeneration. METHODS A scoping review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The databases reviewed were PubMed, SCOPUS, Scientific Electronic Library Online (SciELO), and Web of Science. Studies using stem cells from the oral cavity to promote bone regeneration were included. RESULTS A total of 726 studies were found, of which 27 were selected. The MSCs used to repair bone defects were (I) dental pulp stem cells of permanent teeth, (II) stem cells derived from inflamed dental pulp, (III) stem cells from exfoliated deciduous teeth, (IV) periodontal ligament stem cells, (V) cultured autogenous periosteal cells, (VI) buccal fat pad-derived cells, and (VII) autologous bone-derived mesenchymal stem cells. Stem cells associate with scaffolds to facilitate insertion into the bone defect and to enhance bone regeneration. The biological risk and morbidity of the MSC-grafted site were minimal. Successful bone formation after MSC grafting has been shown for small defects with stem cells from the periodontal ligament and dental pulp as well as larger defects with stem cells from the periosteum, bone, and buccal fat pad. CONCLUSIONS Stem cells of maxillofacial origin are a promising alternative to treat small and large craniofacial bone defects; however, an additional scaffold complement is required for stem cell delivery.
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Affiliation(s)
- Josefa Alarcón-Apablaza
- Research Centre in Dental Sciences (CICO-UFRO), Dental School, Universidad de La Frontera, Temuco 4780000, Chile
- Doctoral Program in Morphological Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile
| | - Ruth Prieto
- Department of Pediatrics and Pediatric Surgery, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile
| | - Mariana Rojas
- Comparative Embryology Laboratory, Program of Anatomy and Developmental Biology, ICBM, Faculty of Medicine, Universidad de Chile, Santiago 8320000, Chile
| | - Ramón Fuentes
- Research Centre in Dental Sciences (CICO-UFRO), Dental School, Universidad de La Frontera, Temuco 4780000, Chile
- Department of Integral Adults Dentistry, Dental School, Universidad de La Frontera, Temuco 4780000, Chile
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Song WP, Jin LY, Zhu MD, Wang H, Xia DS. Clinical trials using dental stem cells: 2022 update. World J Stem Cells 2023; 15:31-51. [PMID: 37007456 PMCID: PMC10052340 DOI: 10.4252/wjsc.v15.i3.31] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/20/2023] [Accepted: 03/08/2023] [Indexed: 03/23/2023] Open
Abstract
For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.
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Affiliation(s)
- Wen-Peng Song
- Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Lu-Yuan Jin
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
| | - Meng-Di Zhu
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China
| | - Hao Wang
- Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Deng-Sheng Xia
- Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.
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Cubuk S, Oduncuoglu BF, Alaaddinoglu EE. The effect of dental pulp stem cells and L-PRF when placed into the extraction sockets of impacted mandibular third molars on the periodontal status of adjacent second molars: a split-mouth, randomized, controlled clinical trial. Oral Maxillofac Surg 2023; 27:59-68. [PMID: 35141806 DOI: 10.1007/s10006-022-01045-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 02/01/2022] [Indexed: 11/28/2022]
Abstract
PURPOSE To compare the clinical and radiographic effectiveness of dental pulp stem cells (DPSCs) seeded onto L-PRF and L-PRF alone in the extraction socket of mandibular third molars. METHODS This study analyzed 13 patients who required surgical removal of impacted bilateral mandibular third molars. The main outcome measures were the probing pocket depth (PPD) and clinical attachment levels (CAL) that were recorded for the adjacent second molars (LM2) at the baseline and 6 months after surgery. The secondary outcomes were radiographic vertical bone loss (VD) and relative bone density (rBD) distal to the LM2. RESULTS Twenty-six LM2s were evaluated. After 6 months, the L-PRF and L-PRF + DPSC groups showed a significant reduction in PPD (1.65 ± 1.01 mm and 1.54 ± 0.78 mm) and CAL (2.23 ± 1.45 mm and 2.12 ± 0.74 mm), respectively. There was no difference between the groups for any periodontal parameters. No significant differences were found between the groups regarding the VD or rBD at the sixth month. CONCLUSIONS This study found that there was a significant improvement regarding the PPD, CAL, and VD measurements with the application of L-PRF, both alone and with the addition of DPSC, at the extraction socket. DPSC did not significantly contribute to the results compared to L-PRF therapy alone. TRIAL REGISTRATION This study was registered on 23 December 2020 on ClinicalTrials.gov under the number NCT04641533.
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Affiliation(s)
- Seçil Cubuk
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Baskent University, 82. Sok. No:26, Bahçelievler, 06490, Ankara, Turkey.
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First-in-Human Study to Investigate the Safety Assessment of Peri-Implant Soft Tissue Regeneration with Micronized-Gingival Connective Tissue: A Pilot Case Series Study. MEDICINES (BASEL, SWITZERLAND) 2023; 10:medicines10010009. [PMID: 36662493 PMCID: PMC9865433 DOI: 10.3390/medicines10010009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 12/28/2022] [Accepted: 12/29/2022] [Indexed: 01/06/2023]
Abstract
Background: We have recently proposed an alternative strategy of free gingival graft (FGG) and connective tissue graft (CTG) using micronized-gingival connective tissues (MGCTs). The advantage of this strategy is that MGCTs from a small piece of maxillary tuberosity can regenerate the keratinized tissue band. However, safety and efficacy have not yet been established in patients. This clinical study was a pilot case series, and the objective was to assess the safety and the preliminary efficacy of MGCTs on peri-implant mucosa regeneration. Methods: This was a pilot interventional, single-center, first-in-human (FIH), open (no masking), uncontrolled, and single-assignment study. A total of 4 patients who needed peri-implant soft tissues reconstruction around dental implants received transplantation of atelocollagen-matrix with MGCTs micronized by the tissue disruptor technique. The duration of intervention was 4 weeks after surgery. Results: This first clinical study demonstrated that using MGCTs did not cause any irreversible adverse events, and it showed the preliminary efficacy for peri-implant soft tissues reconstruction in dental implant therapy. Conclusions: Though further studies are needed on an appropriate scale, as an alternative strategy of FGG or CTG, MGCTs might be promising for peri-implant mucosa reconstruction without requiring a high level of skills and morbidity to harvest graft tissues.
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Forskolin enhanced the osteogenic differentiation of human dental pulp stem cells in vitro and in vivo. J Dent Sci 2023; 18:120-128. [PMID: 36643238 PMCID: PMC9831789 DOI: 10.1016/j.jds.2022.06.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 06/20/2022] [Indexed: 01/18/2023] Open
Abstract
Background/purpose Human dental pulp stem cells (hDPSCs) are multipotent adult stem cells that can differentiate into various lineages such as odontoblasts, osteoblasts, and chondrocytes. Regulation of hDPSCs differentiation with small-molecule compounds can be a useful tool for tissue engineering and regenerative therapy. Forskolin is an agonist of adenylate cyclase that promotes cyclic adenosine monophosphate production. However, the role of Forskolin in regulating the osteogenic differentiation of hDPSCs is still unknown. Materials and methods A cell counting kit-8 (CCK-8) assay was performed to screen out the safety concentrations of Forskolin. Following, quantitative polymerase chain reaction (qPCR) and alizarin red staining were performed to detect bone-related gene expression and mineralized deposit formation. Furthermore, we prepared cell sheets which were followed by a 3D culture for cell pellet formation. Finally, the hDPSC cell pellets were transplanted into immunodeficient mice. Results CCK-8 assay showed 5 μM and 10 μM Forskolin had no significant inhibition on the proliferation of hDPSCs. The qPCR indicated Forskolin (5, 10 μM) enhanced osteogenic differentiation of hDPSCs by upregulating bone-related genes. Alizarin red staining and its quantification analysis demonstrated Forskolin in 5 μM and 10 μM similarly enhanced the mineralized deposit formation of hDPSCs in vitro. After six weeks of transplantation, immunohistochemical stains showed that osteopontin expression and bone formation were significantly boosted in the Forskolin-treated group than in the normal osteogenic inducing group. Conclusion Our results indicate Forskolin enhances osteogenic differentiation of hDPSCs in vitro and boosts bone formation in vivo.
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Moeenzade N, Naseri M, Osmani F, Emadian Razavi F. Dental pulp stem cells for reconstructing bone defects: A systematic review and meta-analysis. J Dent Res Dent Clin Dent Prospects 2022; 16:204-220. [PMID: 37560493 PMCID: PMC10407871 DOI: 10.34172/joddd.2022.034] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 12/02/2022] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND Bone reconstruction with appropriate quality and quantity for dental implant replacement in the alveolar ridge is a challenge in dentistry. As dental pulp stem cells (DPSCs) could be a new perspective in bone regeneration in the future, this study investigated the bone regeneration process by DPSCs. METHODS Electronic searches for articles in the PubMed, EMBASE, and Scopus databases were completed until 21 April 2022. The most important inclusion criteria for selecting in vivo studies reporting quantitative data based on new bone volume and new bone area. The quality assessment was performed based on Cochrane's checklist. RESULTS After the title, abstract, and full-text screening of 762 studies, 23 studies were included. A meta-analysis of 70 studies that reported bone regeneration based on new bone area showed a statistically significant favorable influence on bone tissue regeneration compared to the control groups (P<0.00001, standardized mean difference [SMD]=2.40, 95% CI: 1.55‒3.26; I2=83%). Also, the meta-analysis of 14 studies that reported new bone regeneration based on bone volume showed a statistically significant favorable influence on bone tissue regeneration compared to the control groups (P=0.0003, SMD=1.85, 95% CI: 0.85‒2.85; I2=84%). CONCLUSION This systematic review indicated that DPSCs in tissue regeneration therapy significantly affected bone tissue complex regeneration. However, more and less diverse preclinical studies will enable more powerful meta-analyses in the future.
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Affiliation(s)
- Neda Moeenzade
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Mohsen Naseri
- Cellular and Molecular Research Center, Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Fereshteh Osmani
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Fariba Emadian Razavi
- Clinical Research Development Unit, School of Dentistry, Birjand University of Medical Sciences, Birjand, Iran
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Characterization of Biological Properties of Dental Pulp Stem Cells Grown on an Electrospun Poly(l-lactide- co-caprolactone) Scaffold. MATERIALS 2022; 15:ma15051900. [PMID: 35269131 PMCID: PMC8911644 DOI: 10.3390/ma15051900] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 02/15/2022] [Accepted: 03/01/2022] [Indexed: 02/01/2023]
Abstract
Poly(l-lactide-co-caprolactone) (PLCL) electrospun scaffolds with seeded stem cells have drawn great interest in tissue engineering. This study investigated the biological behavior of human dental pulp stem cells (hDPSCs) grown on a hydrolytically-modified PLCL nanofiber scaffold. The hDPSCs were seeded on PLCL, and their biological features such as viability, proliferation, adhesion, population doubling time, the immunophenotype of hDPSCs and osteogenic differentiation capacity were evaluated on scaffolds. The results showed that the PLCL scaffold significantly supported hDPSC viability/proliferation. The hDPSCs adhesion rate and spreading onto PLCL increased with time of culture. hDPSCs were able to migrate inside the PLCL electrospun scaffold after 7 days of seeding. No differences in morphology and immunophenotype of hDPSCs grown on PLCL and in flasks were observed. The mRNA levels of bone-related genes and their proteins were significantly higher in hDPSCs after osteogenic differentiation on PLCL compared with undifferentiated hDPSCs on PLCL. These results showed that the mechanical properties of a modified PLCL mat provide an appropriate environment that supports hDPSCs attachment, proliferation, migration and their osteogenic differentiation on the PLCL scaffold. The good PLCL biocompatibility with dental pulp stem cells indicates that this mat may be applied in designing a bioactive hDPSCs/PLCL construct for bone tissue engineering.
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Alfayez E, Alghamdi F. Clinical Application of Stem Cell Therapy in Reconstructing Maxillary Cleft Alveolar Bone Defects: A Systematic Review of Randomized Clinical Trials. Cureus 2022; 14:e23111. [PMID: 35425680 PMCID: PMC9002340 DOI: 10.7759/cureus.23111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/12/2022] [Indexed: 11/25/2022] Open
Abstract
An alveolar cleft is the most common congenital bone defect. This systematic review aimed to investigate the use of stem cells for alveolar cleft repair and summarize the outcomes of clinical research studies. The electronic databases PubMed, Scopus, Web of Sciences, and Google Scholar were utilized to search the literature for relevant studies after administering specific inclusion and exclusion criteria. The search included articles that were published from 2011 to 2021 and specific keywords were used in the databases. The search was completed by two independent reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Only four studies satisfied both the inclusion and exclusion criteria and were included in this systematic review. These studies investigated different aspects of bone reconstruction in the maxillary alveolar bone by stem cells, including cell types, clinical applications, biomaterial scaffolds, and follow-up period. The accumulated evidence in this systematic review is limited and insufficient to support the role of stem cell use in bone regeneration of maxillary alveolar bone defects. The outcome of using stem cells was studied only in 57 subjects from the four included studies. Although the noninvasive methods of isolating stem cells make them attractive resources for bone regeneration, more research is required in order to standardize and investigate stem cell therapy. This should be done beforehand in adults in less invasive procedures such as bone defect repair in dentistry prior to considering this type of therapy in this vulnerable patient population.
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Affiliation(s)
- Eman Alfayez
- Oral Biology, Faculty of Dentistry, King Abdulaziz University, Jeddah, SAU
| | - Faisal Alghamdi
- Oral Biology, Faculty of Dentistry, King Abdulaziz University, Jeddah, SAU
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14
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Y Baena AR, Casasco A, Monti M. Hypes and Hopes of Stem Cell Therapies in Dentistry: a Review. Stem Cell Rev Rep 2022; 18:1294-1308. [PMID: 35015212 PMCID: PMC8748526 DOI: 10.1007/s12015-021-10326-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/29/2021] [Indexed: 12/20/2022]
Abstract
One of the most exciting advances in life science research is the development of 3D cell culture systems to obtain complex structures called organoids and spheroids. These 3D cultures closely mimic in vivo conditions, where cells can grow and interact with their surroundings. This allows us to better study the spatio-temporal dynamics of organogenesis and organ function. Furthermore, physiologically relevant organoids cultures can be used for basic research, medical research, and drug discovery. Although most of the research thus far focuses on the development of heart, liver, kidney, and brain organoids, to name a few, most recently, these structures were obtained using dental stem cells to study in vitro tooth regeneration. This review aims to present the most up-to-date research showing how dental stem cells can be grown on specific biomaterials to induce their differentiation in 3D. The possibility of combining engineering and biology principles to replicate and/or increase tissue function has been an emerging and exciting field in medicine. The use of this methodology in dentistry has already yielded many interesting results paving the way for the improvement of dental care and successful therapies.
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Affiliation(s)
- Alessandra Rodriguez Y Baena
- Program in Biomedical Sciences and Engineering, Department of Molecular, Cell, and Developmental Biology, University of California-Santa Cruz, Santa Cruz, CA, 95064, USA
| | - Andrea Casasco
- Department of Public Health, Experimental and Forensic Medicine, Histology and Embryology Unit, University of Pavia, Pavia, Italy.,Dental & Face Center, CDI, Milan, Italy
| | - Manuela Monti
- Department of Public Health, Experimental and Forensic Medicine, Histology and Embryology Unit, University of Pavia, Pavia, Italy. .,Research Center for Regenerative Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
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15
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Desando G, Grigolo B, Deangelles Pereira Florentino Á, Teixeira MW, Barbagallo F, Naro F, da Silva-Júnior VA, Soares AF. Preclinical Evidence of Intra-Articular Autologous Cartilage Micrograft for Osteochondral Repair: Evaluation in a Rat Model. Cartilage 2021; 13:1770S-1779S. [PMID: 34474579 PMCID: PMC8804823 DOI: 10.1177/19476035211042408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE The search for an effective and long-lasting strategy to treat osteochondral defects (OCD) is a great challenge. Regenerative medicine launched a new era of research in orthopaedics for restoring normal tissue functions. The aim of this study was to test the healing potential of Rigenera micrografting technology in a rat model of OCD by investigating 2 cartilage donor sites. METHODS Full-thickness OCD was bilaterally created in the knee joints of rats. Animals were randomly divided into 2 groups based on the anatomical site used for micrograft collection: articular (TO) and xiphoid (XA). Micrograft was injected into the knee via an intra-articular approach. The contralateral joint served as the control. Euthanasia was performed 2 months after the set-up of OCD. Histological evaluations foresaw hematoxylin/eosin and safranin-O/fast green staining, the modified O'Driscoll score, and collagen 1A1 and 2A1 immunostaining. Kruskal-Wallis and the post hoc Dunn test were performed to evaluate differences among groups. RESULTS Histological results showed defect filling in both autologous micrografts. The TO group displayed tissue repair with more hyaline-like characteristics than its control (P < 0.01). A fibrocartilaginous aspect was instead noticed in the XA group. Immunohistochemical assessments on type 2A1 and type 1 collagens confirmed the best histological results in the TO group. CONCLUSIONS TO and XA groups contributed to a different extent to fill the OCD lesions. TO group provided the best histological and immunohistochemical results; therefore, it could be a promising method to treat OCD after the validation in a larger animal model.
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Affiliation(s)
- Giovanna Desando
- Laboratorio RAMSES, IRCCS Istituto
Ortopedico Rizzoli, Bologna, Italy
| | - Brunella Grigolo
- Laboratorio RAMSES, IRCCS Istituto
Ortopedico Rizzoli, Bologna, Italy,Brunella Grigolo, Laboratorio RAMSES, IRCCS
Istituto Ortopedico Rizzoli, Via di Barbiano, 1/10, Bologna, Emilia-Romagna
40136, Italy.
| | | | | | - Federica Barbagallo
- Department of Experimental Medicine,
Sapienza University of Rome, Rome, Italy
| | - Fabio Naro
- Department of Anatomical, Histological,
Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | | | - Anísio Francisco Soares
- Department of Animal Morphology and
Physiology, Federal Rural University of Pernambuco–UFRPE, Brazil
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16
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Astarita C, Arora CL, Trovato L. Tissue regeneration: an overview from stem cells to micrografts. J Int Med Res 2021; 48:300060520914794. [PMID: 32536230 PMCID: PMC7297485 DOI: 10.1177/0300060520914794] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Regenerative medicine represents a major challenge for the scientific community. The choice of the biological sources used, such as stem cells and grafts, is crucial. Stem cell therapy is mainly related to the use of mesenchymal stem cells; however, clinical trials are still needed to investigate their safety. The micrografting technique was conceived by Cicero Parker Meek in 1958. It is based on the principle that by increasing the superficial area of skin grafts and reducing the size of its particles, it is possible to cover an area larger than the original donor site. Stem cells are pluripotent cells that have the capacity to differentiate into all cell types and are self-renewing, whereas micrografts derive from a small fragment of an autologous tissue and exhibit limited differentiative potential compared with stem cells. Therefore, stem cells and micrografts cannot be considered equivalent, although in some cases they exhibit similar regenerative potential, which is the focus of this review. Last, stem cell therapies remain limited because of complex and costly processes, making them not very feasible in clinical practice, whereas obtaining micrografts is generally a one-step procedure that does not require any advanced tissue manipulation.
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Affiliation(s)
- Carlo Astarita
- Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA.,Human Brain Wave, corso Galileo Ferraris 63, 10128 Turin, Italy
| | - Camilla L Arora
- Human Brain Wave, corso Galileo Ferraris 63, 10128 Turin, Italy
| | - Letizia Trovato
- Human Brain Wave, corso Galileo Ferraris 63, 10128 Turin, Italy
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17
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Fagalde P, Reininger D. Oral tissues regeneration using intraoral mesenchymal stem cells. J Clin Exp Dent 2021; 13:e268-e277. [PMID: 33680329 PMCID: PMC7920558 DOI: 10.4317/jced.56810] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 07/02/2020] [Indexed: 01/01/2023] Open
Abstract
Background Oral pathologies or some treatments can cause facial and functional alterations, being fundament to retrieve those functions restoring the original anatomy of the lost tissues. On this purpose, various techniques have been studied, one of these was the tissue engineering. Mesenchymal stem cells (MSC) are multipotent adult stem cells. The MSC in the oral cavity have been striking for regenerative therapies by its high plasticity, good interaction with scaffolds and growth factors, good proliferation and differentiation, they are also easy to obtain. Objective: The objective of this study was to describe the current uses of the intraoral MSC for the regeneration of the tissues of the oral cavity.
Material and Methods An electronic research was made in the databases PubMed, Cochrane Library, Google Scholar, Scopus and EBSCO between 2000 to 2018.
Results 21 articles were included. 13 were studies in vivo and 8 were studies in humans. The site mostly used as a giver site was the dental pulp. Intraoral MSC are able to regenerate the pulp dentin complex, alveolar bone and periodontium.
Conclusions Intraoral MSC come from easy access areas, less traumatic interventions and have high potential to regenerate intraoral tissues in comparison to MSC from other sites of the body which allows a more predictable oral tissues regeneration. Key words:Oral stem cells, oral cavity, regeneration, tissue engineering.
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Affiliation(s)
| | - David Reininger
- DDS, PhD, Master in Oral Surgery and Implantology, Assistant professor, Universidad Mayor, Chile
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18
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Copcu HE, Oztan S. Not Stromal Vascular Fraction (SVF) or Nanofat, but Total Stromal-Cells (TOST): A New Definition. Systemic Review of Mechanical Stromal-Cell Extraction Techniques. Tissue Eng Regen Med 2021; 18:25-36. [PMID: 33231864 PMCID: PMC7862455 DOI: 10.1007/s13770-020-00313-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 10/04/2020] [Accepted: 10/19/2020] [Indexed: 12/25/2022] Open
Abstract
The most important and greatest source in the body for regenerative cells is fat tissue. Obtaining regenerative cells from adipose tissue can be done in two ways: Enzymatic and mechanical. The regenerative cell cocktail obtained by the enzymatic method, including stem cells, is called Stromal vascular fracture (SVF). In the literature, there is no clear definition of regenerative cells obtained by mechanical method. We systematically searched the techniques and definitions for stromal cells obtained from adipose tissue by scanning different databases. To evaluate the mechanical stromal-cell isolation techniques and end products from adipose tissue. Systematic review of English and non-English articles using Embase, PubMed, Web of Science and Google scholar databases. Search terms included Nanofat, fragmented fat, mechanical stromal / stem cell, mechanical SVF, SVF gel. We screened all peer-reviewed articles related with mechanical stromal-cell isolation. Author performed a literature query with the aforementioned key words and databases. A total of 276 publications containing the keywords we searched were reached. In these publications, there are 46 different definitions used to obtain mechanical stromal cells. The term SVF is only suitable for enzymatic methods. A different definition is required for mechanical. The most used term nanofat is also not suitable because the product is not in both "fat" and in "nanoscale". We think that the term total stromal-cells would be the most appropriate definition since both extracellular matrix and all stromal cells are protected in mechanical methods.
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Affiliation(s)
- H. Eray Copcu
- Plastic and Reconstructive Surgery, MEST Medical Services, Cumhuriyet Bulv. No:161/A,1,2 Alsancak, Izmir, Turkey
| | - Sule Oztan
- Plastic and Reconstructive Surgery, MEST Medical Services, Cumhuriyet Bulv. No:161/A,1,2 Alsancak, Izmir, Turkey
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19
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Pourlak T, Pourlak T, Ghodrati M, Mortazavi A, Dolati S, Yousefi M. Usage of stem cells in oral and maxillofacial region. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2020; 122:441-452. [PMID: 33099018 DOI: 10.1016/j.jormas.2020.10.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 09/07/2020] [Accepted: 10/06/2020] [Indexed: 11/30/2022]
Abstract
Malformations of the maxillofacial region has disturbing psychosocial effects and causes enormous socioeconomic concerns. The management of maxillofacial defects caused by congenital anomalies, trauma, osteoporotic fractures, periodontitis, or cancer treatment is challenging for oral and maxillofacial surgeons. Numerous approaches have been recommended for the managing of these deficiencies. The traditional treatment for maxillofacial defects or their repair is an intricate process by autologous bone grafts from the scapula, ribs, fibula, or iliac crest origins. Regenerative medicine is well thought-out as a perfect substitute approach for autologous bone grafts to renovate bone deficiencies. The use of stem cells has improved results and offered a technique to reconstruct craniofacial bone defects. The field of tissue engineering for the regeneration of maxillofacial needs integration of biochemical and biomaterial engineering aspects with cell transplantation to generate better-quality biomimetic scaffolds, prevascularize three-dimensional (3D) tissue structures, and engineer the composite interface of diverse facial tissues. In this review, we have discussed the application of different adult stem cells to repair oral and maxillofacial defects in animal models and clinical trials.
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Affiliation(s)
- T Pourlak
- Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - T Pourlak
- Department of Pathology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - M Ghodrati
- Department of Endodontics, Dental and Periodental Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - A Mortazavi
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - S Dolati
- Physical Medicine and Rehabilitation Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - M Yousefi
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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20
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Granz CL, Gorji A. Dental stem cells: The role of biomaterials and scaffolds in developing novel therapeutic strategies. World J Stem Cells 2020; 12:897-921. [PMID: 33033554 PMCID: PMC7524692 DOI: 10.4252/wjsc.v12.i9.897] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/05/2020] [Accepted: 08/16/2020] [Indexed: 02/06/2023] Open
Abstract
Dental stem cells (DSCs) are self-renewable cells that can be obtained easily from dental tissues, and are a desirable source of autologous stem cells. The use of DSCs for stem cell transplantation therapeutic approaches is attractive due to their simple isolation, high plasticity, immunomodulatory properties, and multipotential abilities. Using appropriate scaffolds loaded with favorable biomolecules, such as growth factors, and cytokines, can improve the proliferation, differentiation, migration, and functional capacity of DSCs and can optimize the cellular morphology to build tissue constructs for specific purposes. An enormous variety of scaffolds have been used for tissue engineering with DSCs. Of these, the scaffolds that particularly mimic tissue-specific micromilieu and loaded with biomolecules favorably regulate angiogenesis, cell-matrix interactions, degradation of extracellular matrix, organized matrix formation, and the mineralization abilities of DSCs in both in vitro and in vivo conditions. DSCs represent a promising cell source for tissue engineering, especially for tooth, bone, and neural tissue restoration. The purpose of the present review is to summarize the current developments in the major scaffolding approaches as crucial guidelines for tissue engineering using DSCs and compare their effects in tissue and organ regeneration.
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Affiliation(s)
- Cornelia Larissa Granz
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
| | - Ali Gorji
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
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21
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Araújo CRG, Astarita C, D’Aquino R, Pelegrine AA. Evaluation of Bone Regeneration in Rat Calvaria Using Bone Autologous Micrografts and Xenografts: Histological and Histomorphometric Analysis. MATERIALS 2020; 13:ma13194284. [PMID: 32992850 PMCID: PMC7579544 DOI: 10.3390/ma13194284] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 09/17/2020] [Accepted: 09/21/2020] [Indexed: 12/11/2022]
Abstract
The aim of this study was to investigate the effect of the use of autologous micrografts obtained by the Rigenera® Micrografting Technology and xenograft on critical size defects created in the calvaria of rats. Forty-eight rats were randomly divided into four groups for each of the two evaluation times (15 and 30 days) (n = 6). After general anesthesia, a 5-mm diameter bone defect was created in the calvaria of each animal. Each defect was filled with the following materials: blood clot, autologous bone graft, xenograft, and xenograft associated with autologous micrografts. Histomorphometric and histological analysis showed that the group that have received the Rigenera® processed autologous micrografts combined with the xenograft and the group that received autologous bone graft resulted in greater bone formation in both time points when compared with the use of the xenograft alone and blood clot.
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Affiliation(s)
- Carlos R. G. Araújo
- Faculdade São Leopoldo Mandic, Instituto São Leopoldo Mandic, Department of Implant Dentistry, Campinas 13045-755, Brazil; (C.R.G.A.); (A.A.P.)
| | - Carlo Astarita
- Human Brain Wave Srl, corso Galileo Ferraris 63, 10128 Turin, Italy;
- Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
- Correspondence:
| | - Riccardo D’Aquino
- Human Brain Wave Srl, corso Galileo Ferraris 63, 10128 Turin, Italy;
| | - André A. Pelegrine
- Faculdade São Leopoldo Mandic, Instituto São Leopoldo Mandic, Department of Implant Dentistry, Campinas 13045-755, Brazil; (C.R.G.A.); (A.A.P.)
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22
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Menchini G, Astarita C. Effects of autologous micrografts on stable bilateral vitiligo: A focus on hand lesions. J Dermatol 2020; 47:1417-1423. [PMID: 32954507 DOI: 10.1111/1346-8138.15564] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 07/01/2020] [Accepted: 07/24/2020] [Indexed: 01/17/2023]
Abstract
Vitiligo is an autoimmune skin disorder characterized by depigmented patches of the skin associated with, among several factors, dysregulation and death of melanocytes. Currently, the treatment of vitiligo is based both on the arrest of the progression of active disease and on the stimulation of the skin repigmentation. The aim of this study was to assess the effects of autologous micrografts and narrowband ultraviolet B (NBUVB) phototherapy for skin repigmentation of patients with bilateral stable vitiligo. Autologous micrografts are derived from mechanical disaggregation of small pieces of the patient's own skin, while phototherapy is a strategy treatment already used. Twenty patients with stable bilateral vitiligo were treated, showing a mean percentage rate of 59.1% at baseline. Combined treatment by autologous micrografts and NBUVB was performed only on the lesions of the hands, and the clinical follow up was performed after 3 and 6 months by photographs taken under Wood's light. After 6 months, we classed 100% of patients as responders. We also reported a mean of repigmentation rate of 36.7% after 3 months and 64.6% after 6 months of treatment. In particular, six of the 20 patients reached a marked repigmentation rate (75-100%), four moderate (51-75%) and 10 mild (26-50%). No adverse effects were observed and no drugs were administrated as co-adjuvant therapy. These results are suggestive of a potential wide use of autologous micrografts associated with NBUVB phototherapy for the treatment of stable vitiligo.
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Affiliation(s)
- Giovanni Menchini
- Dermacademy Institute for Dermatological Sciences and Aesthetic Medicine, Pisa, Italy
| | - Carlo Astarita
- Human Brain Wave Srl, Turin, Italy.,Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, USA
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23
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Marcarelli M, Fiammengo M, Trovato L, Lancione V, Novarese E, Indelli PF, Risitano S. Autologous grafts in the treatment of avascular osteonecrosis of the femoral head. ACTA BIO-MEDICA : ATENEI PARMENSIS 2020; 91:342-349. [PMID: 32420971 PMCID: PMC7569645 DOI: 10.23750/abm.v91i2.8188] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 08/24/2019] [Indexed: 11/23/2022]
Abstract
Background: Osteonecrosis of the femoral head (ONFH) is a frequent orthopedic disease leading to destruction of the hip joint and disabling arthritis. Several procedures have been developed to treat the joint deterioration in case of osteonecrosis, trying to avoid or delay an intervention of total hip replacement, especially in young patients. The aim of this study was to analyze the use of autologous bone micrografts derived from cancellous bone in the management of avascular ONFH. The treatment described was implemented using the Rigenera® protocol to obtain autologous micrografts: small fragments of cancellous bone collected by femoral neck, disaggregated and injected in the necrotic area using an empty screw. Materials and methods: Twenty adult patients affected by avascular ONFH were enrolled in this study; all patients reported a preoperative intermittent coxo-arthrosis and limited function of intra and extra rotation of the hip. Inclusion criteria were an Oxford Hip Score between (OHS) 20 and 39, a Harris hip score (HHS) showing pre-operative poor results (lower than 70 points) and a stage II-IIIA and IIIB according with the classification proposed by the Association Research Circulation Osseous (ARCO). Results: Using an MRI evaluation, after six months, the authors observed a complete regression of necrotic area and the restoration of osseous structure. Clinical outcome has been evaluated at 6-12 and 24 months follow-up. At the final F.U. the HHS rised from poor to good results (mean value at final F.U of 84) while the OHS improved significantly already after 21 days from micrografts injection (mean 35.4 ± 7.5) with an increasing trend until to two-year final FU (mean 37.4 ± 9.5). The full recovery of daily and mild sport activities was reached after 20 and 90 days from intervention, respectively. Conclusion: The results of this study are suggestive for a new approach in the treatment of avascular ONFH assuming a process of bone regeneration based on a dual mechanism of action, biological and mechanical, induced by micrografts and injected using an empty screw as vehicle. (www.actabiomedica.it)
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Affiliation(s)
- Marco Marcarelli
- Department of Orthopaedic Surgery and Traumatology. "Maggiore" Hospital of Chieri. Turin. ITA.
| | - Marco Fiammengo
- Department of Orthopaedic Surgery and Traumatology. "Maggiore" Hospital of Chieri. Turin. ITA.
| | - Letizia Trovato
- Department of nephrology and dialysis, "Regina Margherita" Hospital Turin. ITA.
| | - Vincenzo Lancione
- Department of Orthopaedic Surgery and Traumatology. "Maggiore" Hospital of Chieri. Turin. ITA.
| | - Elvio Novarese
- Department of Orthopaedic Surgery and Traumatology. "Maggiore" Hospital of Chieri. Turin. ITA.
| | - Pier Francesco Indelli
- Department of Orthopaedic Surgery and Bioengineering, Stanford University School of Medicine and the Palo Alto Veterans Affairs Health Care System(PAVAHCS), Palo Alto, CA, USA.
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Oral stem cells in intraoral bone formation. J Oral Biosci 2020; 62:36-43. [DOI: 10.1016/j.job.2019.12.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 11/28/2019] [Accepted: 12/04/2019] [Indexed: 01/08/2023]
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25
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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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Bartold M, Gronthos S, Haynes D, Ivanovski S. Mesenchymal stem cells and biologic factors leading to bone formation. J Clin Periodontol 2019; 46 Suppl 21:12-32. [PMID: 30624807 DOI: 10.1111/jcpe.13053] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 09/23/2018] [Accepted: 10/26/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Physiological bone formation and bone regeneration occurring during bone repair can be considered distinct but similar processes. Mesenchymal stem cells (MSC) and associated biologic factors are crucial to both bone formation and bone regeneration. AIM To perform a narrative review of the current literature regarding the role of MSC and biologic factors in bone formation with the aim of discussing the clinical relevance of in vitro and in vivo animal studies. METHODS The literature was searched for studies on MSC and biologic factors associated with the formation of bone in the mandible and maxilla. The search specifically targeted studies on key aspects of how stem cells and biologic factors are important in bone formation and how this might be relevant to bone regeneration. The results are summarized in a narrative review format. RESULTS Different types of MSC and many biologic factors are associated with bone formation in the maxilla and mandible. CONCLUSION Bone formation and regeneration involve very complex and highly regulated cellular and molecular processes. By studying these processes, new clinical opportunities will arise for therapeutic bone regenerative treatments.
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Affiliation(s)
- Mark Bartold
- School of Dentistry, University of Adelaide, Adelaide, SA, Australia
| | - Stan Gronthos
- Mesenchymal Stem Cell Laboratory, Faculty of Health and Medical Sciences, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
| | - David Haynes
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
| | - Saso Ivanovski
- School of Dentistry, University of Queensland, Brisbane, Qld, Australia
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27
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A Multicentre Study: The Use of Micrografts in the Reconstruction of Full-Thickness Posttraumatic Skin Defects of the Limbs-A Whole Innovative Concept in Regenerative Surgery. Stem Cells Int 2019; 2019:5043518. [PMID: 31885613 PMCID: PMC6915006 DOI: 10.1155/2019/5043518] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 09/06/2019] [Accepted: 10/03/2019] [Indexed: 12/25/2022] Open
Abstract
The skin graft is a surgical technique commonly used in the reconstructive surgery of the limbs, in order to repair skin loss, as well as to repair the donor area of the flaps and cover the dermal substitutes after engraftment. The unavoidable side effect of this technique consists of unaesthetic scars. In order to achieve the healing of posttraumatic ulcers by means of tissue regeneration and to avoid excessive scarring, a new innovative technology based on the application of autologous micrografts, obtained by Rigenera technology, was reported. This technology was able to induce tissue repair by highly viable skin micrografts of 80 micron size achieved by a mechanical disaggregation method. The specific cell population of these micrografts includes progenitor cells, which in association with the fragment of the Extracellular Matrix (ECM) and growth factors derived by patients' own tissue initiate biological processes of regeneration enhancing the wound healing process. We have used this technique in 70 cases of traumatic wounds of the lower and upper limbs, characterized by extensive loss of skin substance and soft tissue. In all cases, we have applied the Rigenera protocol using skin micrografts, achieving in 69 cases the complete healing of wounds in a period between 35 and 84 days. For each patient, the reconstructive outcome was evaluated weekly to assess the efficacy of this technique and any arising complication. A visual analogue scale (VAS) was administered to assess the amount of pain felt after the micrografts' application, whereas we evaluated the scars according to the Vancouver scale and the wound prognosis according to Wound Bed Score. We have thus been able to demonstrate that Rigenera procedure is very effective in stimulating skin regeneration, while reducing the outcome scar.
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Ruiz RG, Rosell JMC, Ceccarelli G, De Sio C, De Angelis GC, Pinto H, Astarita C, Graziano A. Progenitor-cell-enriched micrografts as a novel option for the management of androgenetic alopecia. J Cell Physiol 2019; 235:4587-4593. [PMID: 31643084 DOI: 10.1002/jcp.29335] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 09/30/2019] [Indexed: 01/25/2023]
Abstract
Regenerative medicine is a multidisciplinary field that combines engineering and life science principles to promote regeneration, potentially restoring the physiological condition in diseased tissues. Specifically, the developments of complex grafts enhance the intrinsic regenerative capacity of the host by altering its environment. Autologous micrografts obtained through Rigenera® micrografting technology are able to promote derma and bone regeneration. Androgenetic alopecia (AGA) leads to a progressive thinning of scalp hair affecting 60-70% of the adult population worldwide. Pharmacological treatment offers moderate results and hair transplantation represents the only permanent treatment option. The aim of this study was to demonstrate the role of dermis micrografting in the treatment of AGA by clinical and histological evaluations after 4, 6, and 12 months. Hair growth and density were improved at all indicated times. Those outcomes were also confirmed by the TrichoScan® analysis, reporting an increase of total hair count and density with an increase and reduction of anagen and telogen phases, respectively. Scalp dermoscopic analysis showed an improvement of hair density and histological analysis indicated a clear amelioration of the scalp, development of hair follicles, and a beginning of cuticle formation. Collectively, those results suggest a possible use of the micrografts as a novel therapeutic option in the management of AGA.
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Affiliation(s)
| | | | - Gabriele Ceccarelli
- Department of Public Health, Experimental Medicine and Forensics, Center for Health Technologies, University of Pavia, Pavia, Italy
| | - Ciro De Sio
- Private practice of Plastic Surgeon, Rome, Italy
| | - Gabriella C De Angelis
- Department of Public Health, Experimental Medicine and Forensics, Center for Health Technologies, University of Pavia, Pavia, Italy
| | - Hernan Pinto
- Biomedical Research Institute i2e3, Barcelona, Spain
| | - Carlo Astarita
- Department of R&D, Human Brain Wave, Turin, Italy.,Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania
| | - Antonio Graziano
- Department of R&D, Human Brain Wave, Turin, Italy.,Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania
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Shanbhag S, Suliman S, Pandis N, Stavropoulos A, Sanz M, Mustafa K. Cell therapy for orofacial bone regeneration: A systematic review and meta-analysis. J Clin Periodontol 2019; 46 Suppl 21:162-182. [DOI: 10.1111/jcpe.13049] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 10/17/2018] [Accepted: 10/26/2018] [Indexed: 12/15/2022]
Affiliation(s)
- Siddharth Shanbhag
- Department of Clinical Dentistry; Center for Clinical Dental Research; University of Bergen; Bergen Norway
| | - Salwa Suliman
- Department of Clinical Dentistry; Center for Clinical Dental Research; University of Bergen; Bergen Norway
| | - Nikolaos Pandis
- Department of Orthodontics and Dentofacial Orthopedics; University of Bern; Bern Switzerland
| | - Andreas Stavropoulos
- Department of Periodontology; Faculty of Odontology; Malmö University; Malmö Sweden
| | - Mariano Sanz
- Section of Periodontology; Faculty of Odontology; University Complutense of Madrid; Madrid Spain
| | - Kamal Mustafa
- Department of Clinical Dentistry; Center for Clinical Dental Research; University of Bergen; Bergen Norway
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Uehara M, Shimizu F. Progress report for intractable ulcer and osteomyelitis cases using autologous micrografts. SAGE Open Med Case Rep 2019; 7:2050313X19848301. [PMID: 31105956 PMCID: PMC6503585 DOI: 10.1177/2050313x19848301] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Accepted: 02/05/2019] [Indexed: 11/15/2022] Open
Abstract
Intractable ulcers often occur following primary diseases and have a significant impact on the quality of life of affected subjects. The medical treatments now available include compression and continuous debridement or additional interventions such as advanced wound dressings, local or systemic antibiotics with a mild benefit for the patients in the long term. In this report, we describe the use of autologous micrografts obtained by Rigenera® procedure in the management of two cases of intractable ulcers showing good outcomes for both patients approximately after 30 days from intervention. In the first case, a 74-year-old male with a diagnosis of Fournier's gangrene who underwent several interventions showed a rapid wound epithelization after micrografts application. In the second case, a 63-year-old male affected by a left hallux ulcer with a diagnosis of chronic osteomyelitis also showed a gradual reduction in the ulcer approximately after 1 month from micrografts application.
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Affiliation(s)
- Miyuki Uehara
- Department of Plastic and Reconstructive Surgery, Oita University School of Medicine, Oita, Japan
| | - Fumiaki Shimizu
- Department of Plastic and Reconstructive Surgery, Oita University School of Medicine, Oita, Japan.,Department of Plastic Surgery, Oita University Hospital, Yufu, Japan
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31
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Viganò M, Tessaro I, Trovato L, Colombini A, Scala M, Magi A, Toto A, Peretti G, de Girolamo L. Rationale and pre-clinical evidences for the use of autologous cartilage micrografts in cartilage repair. J Orthop Surg Res 2018; 13:279. [PMID: 30400946 PMCID: PMC6218996 DOI: 10.1186/s13018-018-0983-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 10/19/2018] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND The management of cartilage lesions is an open issue in clinical practice, and regenerative medicine represents a promising approach, including the use of autologous micrografts whose efficacy was already tested in different clinical settings. The aim of this study was to characterize in vitro the effect of autologous cartilage micrografts on chondrocyte viability and differentiation and perform an evaluation of their application in racehorses affected by joint diseases. MATERIALS AND METHODS Matched human chondrocytes and micrografts were obtained from articular cartilage using Rigenera® procedure. Chondrocytes were cultured in the presence or absence of micrografts and chondrogenic medium to assess cell viability and cell differentiation. For the pre-clinical evaluation, three racehorses affected by joint diseases were treated with a suspension of autologous micrografts and PRP in arthroscopy interventions. Clinical and radiographic follow-ups were performed up to 4 months after the procedure. RESULTS Autologous micrografts support the formation of chondrogenic micromasses thanks to their content of matrix and growth factors, such as transforming growth factor β (TGFβ) and insulin-like growth factor 1 (IGF-1). On the other hand, no significant differences were observed on the gene expression of type II collagen, aggrecan, and SOX9. Preliminary data in the treatment of racehorses are suggestive of a potential in vivo use of micrografts to treat cartilage lesions. CONCLUSION The results reported in this study showed the role of articular micrografts in the promoting chondrocyte differentiation suggesting their potential use in the clinical practice to treat articular lesions.
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Affiliation(s)
- Marco Viganò
- IRCCS Istituto Ortopedico Galeazzi, via Riccardo Galeazzi 4, 20161 Milan, Italy
| | - Irene Tessaro
- IRCCS Istituto Ortopedico Galeazzi, via Riccardo Galeazzi 4, 20161 Milan, Italy
| | - Letizia Trovato
- Human Brain Wave, corso Galileo Ferraris 63, 10128 Turin, Italy
| | | | - Marco Scala
- Primus Gel srl, Via Casaregis, 30, 16129 Genoa, Italy
| | - Alberto Magi
- Clinica Veterinaria San Rossore, via delle cascine 149, 56100 Pisa, Italy
| | - Andrea Toto
- Clinica Veterinaria San Rossore, via delle cascine 149, 56100 Pisa, Italy
| | - Giuseppe Peretti
- IRCCS Istituto Ortopedico Galeazzi, via Riccardo Galeazzi 4, 20161 Milan, Italy
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, via Mangiagalli 31, 20133 Milan, Italy
| | - Laura de Girolamo
- IRCCS Istituto Ortopedico Galeazzi, via Riccardo Galeazzi 4, 20161 Milan, Italy
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Ferrarotti F, Romano F, Gamba MN, Quirico A, Giraudi M, Audagna M, Aimetti M. Human intrabony defect regeneration with micrografts containing dental pulp stem cells: A randomized controlled clinical trial. J Clin Periodontol 2018; 45:841-850. [PMID: 29779220 DOI: 10.1111/jcpe.12931] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 04/18/2018] [Accepted: 05/13/2018] [Indexed: 02/06/2023]
Abstract
AIM The goal of this study was to evaluate if dental pulp stem cells (DPSCs) delivered into intrabony defects in a collagen scaffold would enhance the clinical and radiographic parameters of periodontal regeneration. MATERIALS AND METHODS In this randomized controlled trial, 29 chronic periodontitis patients presenting one deep intrabony defect and requiring extraction of one vital tooth were consecutively enrolled. Defects were randomly assigned to test or control treatments which both consisted of the use of minimally invasive surgical technique. The dental pulp of the extracted tooth was mechanically dissociated to obtain micrografts rich in autologous DPSCs. Test sites (n = 15) were filled with micrografts seeded onto collagen sponge, whereas control sites (n = 14) with collagen sponge alone. Clinical and radiographic parameters were recorded at baseline, 6 and 12 months postoperatively. RESULTS Test sites exhibited significantly more probing depth (PD) reduction (4.9 mm versus 3.4 mm), clinical attachment level (CAL) gain (4.5 versus 2.9 mm) and bone defect fill (3.9 versus 1.6 mm) than controls. Moreover, residual PD < 5 mm (93% versus 50%) and CAL gain ≥4 mm (73% versus 29%) were significantly more frequent in the test group. CONCLUSIONS Application of DPSCs significantly improved clinical parameters of periodontal regeneration 1 year after treatment.
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Affiliation(s)
- Francesco Ferrarotti
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Federica Romano
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Mara Noemi Gamba
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Andrea Quirico
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Marta Giraudi
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Martina Audagna
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
| | - Mario Aimetti
- Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy
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33
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Cristaldi M, Mauceri R, Tomasello L, Pizzo G, Pizzolanti G, Giordano C, Campisi G. Dental pulp stem cells for bone tissue engineering: a review of the current literature and a look to the future. Regen Med 2018; 13:207-218. [PMID: 29553875 DOI: 10.2217/rme-2017-0112] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Accepted: 12/04/2017] [Indexed: 12/28/2022] Open
Abstract
The aim of this narrative review is to investigate the implication of mesenchymal stem cells harvested from human dental pulp in in vivo bone tissue regeneration. We focused on studies related to roles of human dental pulp stem cells in in vivo bone regeneration. A total of 1021 studies were identified; after the assessment of eligibility, only 39 studies were included in the review. The evaluated information of the studies regards the experimental strategies (e.g., the isolation method, the scaffold, the in vivo animal models). The overall main evidences highlighted from the analysis are that dental pulp stem cells and human-exfoliated deciduous teeth stem cells supported by a suitable scaffold should be considered a valuable source for bone tissue regeneration.
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Affiliation(s)
- Marta Cristaldi
- Department of Surgical, Oncological & Oral Sciences, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Rodolfo Mauceri
- Department of Surgical, Oncological & Oral Sciences, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Laura Tomasello
- Biomedical Department of Internal & Specialist Medicine (DIBIMIS), Laboratory of Regenerative Medicine, Section of Endocrinology, Diabetology & Metabolism, University of Palermo, Piazza delle Cliniche 2, 90127, Palermo, Italy
| | - Giuseppe Pizzo
- Department of Surgical, Oncological & Oral Sciences, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Giuseppe Pizzolanti
- Biomedical Department of Internal & Specialist Medicine (DIBIMIS), Laboratory of Regenerative Medicine, Section of Endocrinology, Diabetology & Metabolism, University of Palermo, Piazza delle Cliniche 2, 90127, Palermo, Italy
| | - Carla Giordano
- Biomedical Department of Internal & Specialist Medicine (DIBIMIS), Laboratory of Regenerative Medicine, Section of Endocrinology, Diabetology & Metabolism, University of Palermo, Piazza delle Cliniche 2, 90127, Palermo, Italy
| | - Giuseppina Campisi
- Department of Surgical, Oncological & Oral Sciences, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
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Cristaldi M, Mauceri R, Tomasello L, Pizzo G, Pizzolanti G, Giordano C, Campisi G. Dental pulp stem cells for bone tissue engineering: a review of the current literature and a look to the future. Regen Med 2018. [DOI: 10.2217/rme-2017-0112 10.2217/rme-2017-0112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
The aim of this narrative review is to investigate the implication of mesenchymal stem cells harvested from human dental pulp in in vivo bone tissue regeneration. We focused on studies related to roles of human dental pulp stem cells in in vivo bone regeneration. A total of 1021 studies were identified; after the assessment of eligibility, only 39 studies were included in the review. The evaluated information of the studies regards the experimental strategies (e.g., the isolation method, the scaffold, the in vivo animal models). The overall main evidences highlighted from the analysis are that dental pulp stem cells and human-exfoliated deciduous teeth stem cells supported by a suitable scaffold should be considered a valuable source for bone tissue regeneration.
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Affiliation(s)
- Marta Cristaldi
- Department of Surgical, Oncological & Oral Sciences, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Rodolfo Mauceri
- Department of Surgical, Oncological & Oral Sciences, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Laura Tomasello
- Biomedical Department of Internal & Specialist Medicine (DIBIMIS), Laboratory of Regenerative Medicine, Section of Endocrinology, Diabetology & Metabolism, University of Palermo, Piazza delle Cliniche 2, 90127, Palermo, Italy
| | - Giuseppe Pizzo
- Department of Surgical, Oncological & Oral Sciences, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Giuseppe Pizzolanti
- Biomedical Department of Internal & Specialist Medicine (DIBIMIS), Laboratory of Regenerative Medicine, Section of Endocrinology, Diabetology & Metabolism, University of Palermo, Piazza delle Cliniche 2, 90127, Palermo, Italy
| | - Carla Giordano
- Biomedical Department of Internal & Specialist Medicine (DIBIMIS), Laboratory of Regenerative Medicine, Section of Endocrinology, Diabetology & Metabolism, University of Palermo, Piazza delle Cliniche 2, 90127, Palermo, Italy
| | - Giuseppina Campisi
- Department of Surgical, Oncological & Oral Sciences, University of Palermo, Via del Vespro 129, 90127, Palermo, Italy
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Daniela Ferreira Araújo BENÍCIO, Luciana Oliveira PEREIRA, Izabel Cristina Rodrigues da SILVA, Ricardo Bentes AZEVEDO, Ana Cristina Barreto BEZERRA. Culture of human dental pulp cells at variable times post-tooth extraction. Braz Oral Res 2018; 32:e003. [DOI: 10.1590/1807-3107bor-2018.vol32.0003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 12/12/2017] [Indexed: 01/09/2023] Open
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36
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Leyendecker Junior A, Gomes Pinheiro CC, Lazzaretti Fernandes T, Franco Bueno D. The use of human dental pulp stem cells for in vivo bone tissue engineering: A systematic review. J Tissue Eng 2018; 9:2041731417752766. [PMID: 29375756 PMCID: PMC5777558 DOI: 10.1177/2041731417752766] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 12/13/2017] [Indexed: 12/20/2022] Open
Abstract
Dental pulp represents a promising and easily accessible source of mesenchymal stem cells for clinical applications. Many studies have investigated the use of human dental pulp stem cells and stem cells isolated from the dental pulp of human exfoliated deciduous teeth for bone tissue engineering in vivo. However, the type of scaffold used to support the proliferation and differentiation of dental stem cells, the animal model, the type of bone defect created, and the methods for evaluation of results were extremely heterogeneous among these studies conducted. With this issue in mind, the main objective of this study is to present and summarize, through a systematic review of the literature, in vivo studies in which the efficacy of human dental pulp stem cells and stem cells from human exfoliated deciduous teeth (SHED) for bone regeneration was evaluated. The article search was conducted in PubMed/MEDLINE and Web of Science databases. Original research articles assessing potential of human dental pulp stem cells and SHED for in vivo bone tissue engineering, published from 1984 to November 2017, were selected and evaluated in this review according to the following eligibility criteria: published in English, assessing dental stem cells of human origin and evaluating in vivo bone tissue formation in animal models or in humans. From the initial 1576 potentially relevant articles identified, 128 were excluded due to the fact that they were duplicates and 1392 were considered ineligible as they did not meet the inclusion criteria. As a result, 56 articles remained and were fully analyzed in this systematic review. The results obtained in this systematic review open new avenues to perform bone tissue engineering for patients with bone defects and emphasize the importance of using human dental pulp stem cells and SHED to repair actual bone defects in an appropriate animal model.
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Rodriguez Y Baena R, D'Aquino R, Graziano A, Trovato L, Aloise AC, Ceccarelli G, Cusella G, Pelegrine AA, Lupi SM. Autologous Periosteum-Derived Micrografts and PLGA/HA Enhance the Bone Formation in Sinus Lift Augmentation. Front Cell Dev Biol 2017; 5:87. [PMID: 29021982 PMCID: PMC5623661 DOI: 10.3389/fcell.2017.00087] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Accepted: 09/12/2017] [Indexed: 12/30/2022] Open
Abstract
Sinus lift augmentation is a procedure required for the placement of a dental implant, whose success can be limited by the quantity or quality of available bone. To this purpose, the first aim of the current study was to evaluate the ability of autologous periosteum-derived micrografts and Poly(lactic-co-glycolic acid) (PLGA) supplemented with hydroxyl apatite (HA) to induce bone augmentation in the sinus lift procedure. Secondly, we compared the micrograft's behavior with respect to biomaterial alone, including Bio-Oss® and PLGA/HA, commercially named Alos. Sinus lift procedure was performed on 24 patients who required dental implants and who, according to the study design and procedure performed, were divided into three groups: group A (Alos + periosteum-derived micrografts); group B (Alos alone); and group C (Bio-Oss® alone). Briefly, in group A, a small piece of periosteum was collected from each patient and mechanically disaggregated by Rigenera® protocol using the Rigeneracons medical device. This protocol allowed for the obtainment of autologous micrografts, which in turn were used to soak the Alos scaffold. At 6 months after the sinus lift procedure and before the installation of dental implants, histological and radiographic evaluations in all three groups were performed. In group A, where sinus lift augmentation was performed using periosteum-derived micrografts and Alos, the bone regeneration was much faster than in the control groups where it was performed with Alos or Bio-Oss® alone (groups B and C, respectively). In addition, the radiographic evaluation in the patients of group A showed a radio-opacity after 4 months, while after 6 months, the prosthetic rehabilitation was improved and was maintained after 2 years post-surgery. In summary, we report on the efficacy of periosteum-derived micrografts and Alos to augment sinus lift in patients requiring dental implants. This efficacy is supported by an increased percentage of vital mineralized tisssue in the group treated with both periosteum-derived micrografts and Alos, with respect to the control group of Alos or Bio-Oss® alone, as confirmed by histological analysis and radiographic evaluations at 6 months from treatment.
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Affiliation(s)
- Ruggero Rodriguez Y Baena
- Department of Clinical Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Riccardo D'Aquino
- Private Practice, Turin, Italy.,Human Brain Wave S.r.L., Turin, Italy
| | - Antonio Graziano
- Human Brain Wave S.r.L., Turin, Italy.,Sbarro Health Research Organization (SHRO), Temple University of Philadelphia, Philadelphia, PA, United States
| | | | - Antonio C Aloise
- Department of Implantology, São Leopoldo Mandic Institute and Research Center, Campinas, Brazil
| | - Gabriele Ceccarelli
- Department of Public Health, Experimental Medicine and Forensics, University of Pavia, Pavia, Italy.,Centre for Health Technologies, University of Pavia, Pavia, Italy
| | - Gabriella Cusella
- Department of Public Health, Experimental Medicine and Forensics, University of Pavia, Pavia, Italy.,Centre for Health Technologies, University of Pavia, Pavia, Italy
| | - André A Pelegrine
- Department of Implantology, São Leopoldo Mandic Institute and Research Center, Campinas, Brazil
| | - Saturnino M Lupi
- Department of Clinical Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
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In Vitro and In Vivo Dentinogenic Efficacy of Human Dental Pulp-Derived Cells Induced by Demineralized Dentin Matrix and HA-TCP. Stem Cells Int 2017; 2017:2416254. [PMID: 28761445 PMCID: PMC5518496 DOI: 10.1155/2017/2416254] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2017] [Revised: 04/26/2017] [Accepted: 05/03/2017] [Indexed: 01/09/2023] Open
Abstract
Human dental pulp cells have been known to have the stem cell features such as self-renewal and multipotency. These cells are differentiated into hard tissue by addition of proper cytokines and biomaterials. Hydroxyapatite-tricalcium phosphates (HA-TCPs) are essential components of hard tissue and generally used as a biocompatible material in tissue engineering of bone. Demineralized dentin matrix (DDM) has been reported to increase efficiency of bone induction. We compared the efficiencies of osteogenic differentiation and in vivo bone formation of HA-TCP and DDM on human dental pulp stem cells (hDPSCs). DDM contains inorganic components as with HA-TCP, and organic components such as collagen type-1. Due to these components, osteoinduction potential of DDM on hDPSCs was remarkably higher than that of HA-TCP. However, the efficiencies of in vivo bone formation are similar in HA-TCP and DDM. Although osteogenic gene expression and bone formation in immunocompromised nude mice were similar levels in both cases, dentinogenic gene expression level was slightly higher in DDM transplantation than in HA-TCP. All these results suggested that in vivo osteogenic potentials in hDPSCs are induced with both HA-TCP and DDM by osteoconduction and osteoinduction, respectively. In addition, transplantation of hDPSCs/DDM might be more effective for differentiation into dentin.
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Noda S, Sumita Y, Ohba S, Yamamoto H, Asahina I. Soft tissue engineering with micronized-gingival connective tissues. J Cell Physiol 2017; 233:249-258. [PMID: 28233312 DOI: 10.1002/jcp.25871] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Accepted: 02/22/2017] [Indexed: 01/01/2023]
Abstract
The free gingival graft (FGG) and connective tissue graft (CTG) are currently considered to be the gold standards for keratinized gingival tissue reconstruction and augmentation. However, these procedures have some disadvantages in harvesting large grafts, such as donor-site morbidity as well as insufficient gingival width and thickness at the recipient site post-treatment. To solve these problems, we focused on an alternative strategy using micronized tissue transplantation (micro-graft). In this study, we first investigated whether transplantation of micronized gingival connective tissues (MGCTs) promotes skin wound healing. MGCTs (≤100 µm) were obtained by mincing a small piece (8 mm3 ) of porcine keratinized gingiva using the RIGENERA system. The MGCTs were then transplanted to a full skin defect (5 mm in diameter) on the dorsal surface of immunodeficient mice after seeding to an atelocollagen matrix. Transplantations of atelocollagen matrixes with and without micronized dermis were employed as experimental controls. The results indicated that MGCTs markedly promote the vascularization and epithelialization of the defect area 14 days after transplantation compared to the experimental controls. After 21 days, complete wound closure with low contraction was obtained only in the MGCT grafts. Tracking analysis of transplanted MGCTs revealed that some mesenchymal cells derived from MGCTs can survive during healing and may function to assist in wound healing. We propose here that micro-grafting with MGCTs represents an alternative strategy for keratinized tissue reconstruction that is characterized by low morbidity and ready availability.
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Affiliation(s)
- Sawako Noda
- Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Yoshinori Sumita
- Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Seigo Ohba
- Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hideyuki Yamamoto
- Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Izumi Asahina
- Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Emerging Perspectives in Scaffold for Tissue Engineering in Oral Surgery. Stem Cells Int 2017; 2017:4585401. [PMID: 28337223 PMCID: PMC5346390 DOI: 10.1155/2017/4585401] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 02/02/2017] [Indexed: 01/09/2023] Open
Abstract
Bone regeneration is currently one of the most important and challenging tissue engineering approaches in regenerative medicine. Bone regeneration is a promising approach in dentistry and is considered an ideal clinical strategy in treating diseases, injuries, and defects of the maxillofacial region. Advances in tissue engineering have resulted in the development of innovative scaffold designs, complemented by the progress made in cell-based therapies. In vitro bone regeneration can be achieved by the combination of stem cells, scaffolds, and bioactive factors. The biomimetic approach to create an ideal bone substitute provides strategies for developing combined scaffolds composed of adult stem cells with mesenchymal phenotype and different organic biomaterials (such as collagen and hyaluronic acid derivatives) or inorganic biomaterials such as manufactured polymers (polyglycolic acid (PGA), polylactic acid (PLA), and polycaprolactone). This review focuses on different biomaterials currently used in dentistry as scaffolds for bone regeneration in treating bone defects or in surgical techniques, such as sinus lift, horizontal and vertical bone grafts, or socket preservation. Our review would be of particular interest to medical and surgical researchers at the interface of cell biology, materials science, and tissue engineering, as well as industry-related manufacturers and researchers in healthcare, prosthetics, and 3D printing, too.
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