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Ghiasi M, Kheirandish Zarandi P, Dayani A, Salimi A, Shokri E. Potential therapeutic effects and nano-based delivery systems of mesenchymal stem cells and their isolated exosomes to alleviate acute respiratory distress syndrome caused by COVID-19. Regen Ther 2024; 27:319-328. [PMID: 38650667 PMCID: PMC11035022 DOI: 10.1016/j.reth.2024.03.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 03/03/2024] [Accepted: 03/15/2024] [Indexed: 04/25/2024] Open
Abstract
The severe respiratory effects of the coronavirus disease 2019 (COVID-19) pandemic have necessitated the immediate development of novel treatments. The majority of COVID-19-related fatalities are due to acute respiratory distress syndrome (ARDS). Consequently, this virus causes massive and aberrant inflammatory conditions, which must be promptly managed. Severe respiratory disorders, notably ARDS and acute lung injury (ALI), may be treated safely and effectively using cell-based treatments, mostly employing mesenchymal stem cells (MSCs). Since the high potential of these cells was identified, a great deal of research has been conducted on their use in regenerative medicine and complementary medicine. Multiple investigations have demonstrated that MSCs and their products, especially exosomes, inhibit inflammation. Exosomes serve a critical function in intercellular communication by transporting molecular cargo from donor cells to receiver cells. MSCs and their derived exosomes (MSCs/MSC-exosomes) may improve lung permeability, microbial and alveolar fluid clearance, and epithelial and endothelial repair, according to recent studies. This review focuses on COVID-19-related ARDS clinical studies involving MSCs/MSC-exosomes. We also investigated the utilization of Nano-delivery strategies for MSCs/MSC-exosomes and anti-inflammatory agents to enhance COVID-19 treatment.
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Affiliation(s)
- Mohsen Ghiasi
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | | | - Abdolreza Dayani
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Salimi
- Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ehsan Shokri
- Department of Nanotechnology, Agricultural Biotechnology Research Institute of Iran (ABRII), Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
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2
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Ivanovski S, Han P, Peters O, Sanz M, Bartold P. The Therapeutic Use of Dental Mesenchymal Stem Cells in Human Clinical Trials. J Dent Res 2024; 103:1173-1184. [PMID: 39370700 PMCID: PMC11562285 DOI: 10.1177/00220345241261900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/08/2024] Open
Abstract
Mesenchymal stem cells (MSCs), characterized by their undifferentiated and multipotent nature, can be derived from various sources, including bone marrow, adipose, and dental tissues. Among these, dental MSCs (DSCs) exhibit universal MSC characteristics and are attracting considerable attention for regenerating oral and craniofacial tissues. This review provides a contemporary overview of recently published clinical studies using DSCs for various orodental and maxillofacial regenerative applications, including bone, periodontal, and endodontic regeneration. It also explores the utilization of DSCs in treating systemic conditions, exemplified by their application in managing conditions such as COVID-19 and osteoarthritis. The available evidence underscores the potential of DSCs and their secretome as efficacious tools in regenerative medicine for both dental and nondental clinical applications, supporting the continued promise of stem cell-based therapies. It is nevertheless evident that there are a number of important challenges that restrict the widespread utilization of DSCs, namely, difficulty in standardizing autologous preparations, insufficient cell surface marker characterization, high production costs, and regulatory compliance requirements. Further, the unique requirements of dental applications, especially complex structures such as the periodontium, where temporospatial control over the healing process is required, necessitate the combination of stem cells with appropriate scaffolds according to the principles of tissue engineering. There is currently insufficient evidence to support the clinical translation of DSCs into clinical practice, and phase 3 clinical trials with standardized protocols for cell sourcing, propagation, dosing, and delivery are required to move the field forward. In summary, this review provides a contemporary overview of the evolving landscape of stem cell therapy, offering insights into the latest developments and trends as well as the challenges that need to be addressed for the widespread application of DSC-based cell therapies.
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Affiliation(s)
- S. Ivanovski
- The University of Queensland, School of Dentistry, Brisbane, QLD, Australia
| | - P. Han
- The University of Queensland, School of Dentistry, Brisbane, QLD, Australia
- The University of Queensland, School of Dentistry, Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), Brisbane, QLD, Australia
| | - O.A. Peters
- The University of Queensland, School of Dentistry, Brisbane, QLD, Australia
| | - M. Sanz
- ETEP (Etiology and Therapy of Periodontal and Peri-implant Diseases) Research Group, Faculty of Odontology, University Complutense of Madrid, Plaza Ramón y Cajalsn (Ciudad Universitaria), Madrid, Spain
| | - P.M. Bartold
- The University of Queensland, School of Dentistry, Brisbane, QLD, Australia
- The University of Adelaide, School of Dentistry, Adelaide, SA, Australia
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Yadav P, Vats R, Bano A, Namdev R, Bhardwaj R. Ameliorative potential of stem cells from human exfoliated deciduous teeth (SHED) in preclinical studies: A meta-analysis. Regen Ther 2023; 24:117-134. [PMID: 37441223 PMCID: PMC10333108 DOI: 10.1016/j.reth.2023.06.004] [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: 02/24/2023] [Revised: 05/27/2023] [Accepted: 06/07/2023] [Indexed: 07/15/2023] Open
Abstract
The preclinical and clinical role of mesenchymal stem cells from various adult sources is extensively investigated and established in regenerative medicine. However, the comprehensive exploration of the therapeutic potential of Stem cells from human exfoliated deciduous teeth (SHED) is inadequate. Therefore, we performed a systematic meta-analysis of preclinical animal model studies in several diseases to provide insight into SHED's efficacy and therapeutic potential. Two blinded and independent investigators searched the available online databases and scrutinized the included studies. Meta-analysis was performed to evaluate the pooled effect estimate of intervention of SHED by Review Manager 5.4.1. To investigate the therapeutic efficacy of SHED intervention, we also analyzed the test of heterogeneity (I2), overall effect (Z), sensitivity, and publication bias. Among the 2156 scrutinized studies, 40 were included and evaluated as per inclusion and exclusion criteria. The intervention of SHED and its derivatives in several diseases depicted statistically significant therapeutic effects in periodontitis, pulpitis, spinal cord injury, parkinson's disease, alzheimer's disease, focal cerebral ischemia, peripheral nerve injury, and retinal pigmentosa. SHED also improved levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin in liver fibrosis . In autoimmune diseases also, values were significant. SHED also showed a statistically significant reduction of wound healing area and new bone formation in bone defects. The pooled effect estimates of included preclinical studies demonstrated a statistically significant therapeutic effect of SHED in numerous diseases. Based on our data, it is suggested that the potential of SHED may be implemented in clinical trials after conducting a few more preclinical studies.
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Affiliation(s)
- Pooja Yadav
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
| | - Ravina Vats
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
| | - Afsareen Bano
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
| | - Ritu Namdev
- Dept. of Pediatric Dentistry, Post Graduate Institute of Dental Sciences, Rohtak, 124001, India
| | - Rashmi Bhardwaj
- Stem Cell Biology Laboratory, Centre for Medical Biotechnology, Maharshi Dayanand University Rohtak, 124001, India
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Liu Y, Li X, Liu S, Du J, Xu J, Liu Y, Guo L. The changes and potential effects of zinc homeostasis in periodontitis microenvironment. Oral Dis 2023; 29:3063-3077. [PMID: 35996971 DOI: 10.1111/odi.14354] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 07/28/2022] [Accepted: 08/14/2022] [Indexed: 11/29/2022]
Abstract
Zinc is a very important and ubiquitous element, which is present in oral environment, daily diet, oral health products, dental restorative materials, and so on. However, there is a lack of attention to the role of both extracellular or intracellular zinc in the progression of periodontitis and periodontal regeneration. This review summarizes the characteristics of immunological microenvironment and host cells function in several key stages of periodontitis progression, and explores the regulatory effect of zinc during this process. We find multiple evidence indicate that zinc may be involved and play a key role in the stages of immune defense, inflammatory response and bone remodeling. Zinc supplementation in an appropriate dose range or regulation of zinc transport proteins can promote periodontal regeneration by either enhancing immune defense or up-regulating local cells proliferation and differentiation functions. Therefore, zinc homeostasis is essential in periodontal remodeling and regeneration. More attention is suggested to be focused on zinc homeostasis regulation and consider it as a potential strategy in the studies on periodontitis treatment, periodontal-guided tissue regeneration, implant material transformation, and so on.
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Affiliation(s)
- Yitong Liu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiaoyan Li
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Siyan Liu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Juan Du
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Junji Xu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yi Liu
- Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China
- Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Lijia Guo
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
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Nguyen-Thi TD, Nguyen-Huynh BH, Vo-Hoang TT, Nguyen-Thanh T. Stem cell therapies for periodontal tissue regeneration: A meta-analysis of clinical trials. J Oral Biol Craniofac Res 2023; 13:589-597. [PMID: 37576801 PMCID: PMC10415796 DOI: 10.1016/j.jobcr.2023.07.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 07/04/2023] [Indexed: 08/15/2023] Open
Abstract
Objective Stem cell therapy in periodontal tissue regeneration has reported optimistic regenerative results; evidence supporting its superiority over conventional methods is still ambiguous. Therefore, this meta-analysis aims to evaluate the therapeutic effects of stem cells in human periodontal regeneration. Design A literature search was conducted to retrieve relevant articles on periodontal regeneration in stem cell therapy. A meta-analysis of the studies was conducted using the Stata software. Results Fifteen studies that examined the effect of stem cell therapies on periodontal tissue regeneration in 369 patients were selected from databases. Regardless of the various types of cells, both odontogenic (periodontal ligament, dental pulp, gingiva stem cell) and non-odontogenic (bone marrow, periosteum-derived, and umbilical cord stem cells), the cell therapies witnessed significant improvements in terms of clinical attachment level (SMD, -0.67; 95CI, -0.90 to -0.43), probing depth (SMD, -0.76; 95% CI, -1.21 to - 0.31), radiographic intrabony defect depth (SMD, -0.87; 95% CI, -1.52 to -0.23), and histomorphometric analysis of mineralized bone (SMD, 0.80; 95% CI, 0.42 to 1.19) when compared to traditional without-cell treatment in patients. However, evidence on gingival recession, alveolar thickness gain, bone mineral density of bone core, and bone volume fraction of bone core outcomes did not reach statistical significance. Conclusions Evidence suggests that the implementation of stem cell therapies in reconstructing compromised gingiva and alveolar bone tissue produces positive outcomes compared with conventional approaches. However, further well-designed investigations are needed to comprehensively identify the most effective source of cells and biomaterials for each case.
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Affiliation(s)
- Thuy-Duong Nguyen-Thi
- Odonto-stomatology Faculty, University of Medicine and Pharmacy, Hue University, 6 Ngo Quyen Street, Hue, 49000, Viet Nam
| | - Bao-Hung Nguyen-Huynh
- Odonto-stomatology Faculty, University of Medicine and Pharmacy, Hue University, 6 Ngo Quyen Street, Hue, 49000, Viet Nam
| | - Thuy-Tien Vo-Hoang
- Odonto-stomatology Faculty, University of Medicine and Pharmacy, Hue University, 6 Ngo Quyen Street, Hue, 49000, Viet Nam
| | - Tung Nguyen-Thanh
- Faculty of Basic Science, University of Medicine and Pharmacy, Hue University, 6 Ngo Quyen Street, Hue, 49000, Viet Nam
- Institute of Biomedicine, University of Medicine and Pharmacy, Hue University, 6 Ngo Quyen Street, Hue, 49000, Viet Nam
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Sun L, Du X, Kuang H, Sun H, Luo W, Yang C. Stem cell-based therapy in periodontal regeneration: a systematic review and meta-analysis of clinical studies. BMC Oral Health 2023; 23:492. [PMID: 37454056 PMCID: PMC10350264 DOI: 10.1186/s12903-023-03186-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 06/29/2023] [Indexed: 07/18/2023] Open
Abstract
BACKGROUND Periodontitis is a common and chronic inflammatory disease characterized by irreversible destruction of the tooth surrounding tissues, especially intrabony defects, which eventually lead to tooth loss. In recent years, stem cell-based therapy for periodontitis has been gradually applied to the clinic, but whether stem cell-based therapy plays a positive role in periodontal regeneration is unclear at present. METHODS The clinical studies related to the evaluation of mesenchymal stem cells for periodontal regeneration in PubMed, Cochrane Central Register of Controlled trials (CENTRAL), Web of Science (WOS), Embase, Scopus, Wanfang and China national knowledge infrastructure (CNKI) databases were searched in June 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell free therapy for the treatment periodontitis, and to have a follow-up for at least six months. Two evaluators searched, screened, and assessed the quality and the risk of bias in the included studies independently. Review Manager 5.4 software was used to perform the meta-analysis, and GRADEpro GDT was used to evaluate the level of the evidence. RESULTS Five randomized controlled trials (RCTs) including 118 patients were analyzed. The results of this meta-analysis demonstrated that stem cell-based therapy showed better therapeutic effects on clinical attachment level (CAL) (MD = - 1.18, 95% CI = - 1.55, - 0.80, P < 0.00001), pocket probing depth (PPD) (MD = - 0.75, 95% CI = - 1.35, - 0.14, P = 0.020), and linear distance from bone crest to bottom of defect (BC-BD)( MD = - 0.95, 95% CI = - 1.67, - 0.23, P = 0.010) compared with cell-free group. However, stem cell-based therapy presented insignificant effects on gingival recession (P = 0.14), linear distance from cementoenamel junction to bottom of defect (P = 0.05). CONCLUSION The results demonstrate that stem cell-based therapy may be beneficial for CAL, PPD and BC-BD. Due to the limited number of studies included, the strength of the results in this analysis was affected to a certain extent. The high-quality RCTs with large sample size, multi-blind, multi-centric are still required, and the methodological and normative clinical study protocol should be established and executed in the future.
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Affiliation(s)
- Liang Sun
- Center of Stomatology, The Second Affiliated Hospital of Soochow University, No 1055 Sanxiang Road, 215004, Soochow, Jiangsu, China
| | - Xinya Du
- Department of Stomatology, The People's Hospital of Longhua, 38 Jinglong Jianshe Road, 518109, Shenzhen, Guangdong, China
| | - Huifang Kuang
- Department of Stomatology, The First Affiliated Hospital of Hainan Medical University, 570102, Haikou, Hainan, China
- School of Stomatology, Hainan Medical University, 571199, Haikou, Hainan, China
| | - Honglan Sun
- Department of Stomatology, The First Affiliated Hospital of Hainan Medical University, 570102, Haikou, Hainan, China
- School of Stomatology, Hainan Medical University, 571199, Haikou, Hainan, China
| | - Wen Luo
- Department of Stomatology, The First Affiliated Hospital of Hainan Medical University, 570102, Haikou, Hainan, China
- School of Stomatology, Hainan Medical University, 571199, Haikou, Hainan, China
| | - Chao Yang
- Department of Stomatology, The People's Hospital of Longhua, 38 Jinglong Jianshe Road, 518109, Shenzhen, Guangdong, China.
- Research and Development Department, Shenzhen Uni-medica technology Co., Ltd, Liuxian Culture Park, 518051, Shenzhen, Guangdong, China.
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Wei X, Liu Q, Liu L, Tian W, Wu Y, Guo S. Periostin plays a key role in maintaining the osteogenic abilities of dental follicle stem cells in the inflammatory microenvironment. Arch Oral Biol 2023; 153:105737. [PMID: 37320885 DOI: 10.1016/j.archoralbio.2023.105737] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 06/17/2023]
Abstract
OBJECTIVE This study aimed to explore the effect of periostin in the osteogenic abilities of dental follicle stem cells (DFSCs) and DFSC sheets in the inflammatory microenvironment. DESIGN DFSCs were isolated from dental follicles and identified. A lentiviral vector was used to knock down periostin in DFSCs. 250 ng/ml lipopolysaccharide from Porphyromonas gingivalis (P.g-LPS) was used to construct the inflammatory microenvironment. Osteogenic differentiation was evaluated by alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot. The formation of extracellular matrix was assessed by qRT-PCR and immunofluorescence. The expressions of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) were measured by western blot. RESULTS Knockdown of periostin inhibited osteogenic differentiation and promoted adipogenic differentiation of DFSCs. In an inflammatory microenvironment, knockdown of periostin attenuated the proliferation and osteogenic differentiation of DFSCs. Knockdown of periostin inhibited the formation of extracellular matrix collagen I (COL-I), fibronectin, and laminin in DFSC sheets, but did not affect the expression of osteogenesis-related markers alkaline phosphatase (ALP) and osteocalcin (OCN). In the inflammatory microenvironment, knocking down periostin inhibited the expression of OCN and OPG in DFSC sheets, and promoted the expression of RANKL. CONCLUSION Periostin played a key role in maintaining the osteogenic abilities of DFSCs and DFSC sheets in the inflammatory microenvironment and might be an important molecule in the process of DFSCs coping with inflammatory microenvironment and promoting periodontal tissues regeneration.
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Affiliation(s)
- Xiuqun Wei
- State Key Laboratory of Oral Diseases, &National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, PR China; Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu 610041, PR China; Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China
| | - Qian Liu
- State Key Laboratory of Oral Diseases, &National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, PR China; Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu 610041, PR China; Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China
| | - Li Liu
- State Key Laboratory of Oral Diseases, &National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, PR China; Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu 610041, PR China; Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China
| | - Weidong Tian
- State Key Laboratory of Oral Diseases, &National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, PR China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China
| | - Yafei Wu
- State Key Laboratory of Oral Diseases, &National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, PR China; Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China.
| | - Shujuan Guo
- State Key Laboratory of Oral Diseases, &National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, PR China; Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu 610041, PR China; Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China.
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Yang C, Du XY, Luo W. Clinical application prospects and transformation value of dental follicle stem cells in oral and neurological diseases. World J Stem Cells 2023; 15:136-149. [PMID: 37181000 PMCID: PMC10173814 DOI: 10.4252/wjsc.v15.i4.136] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/18/2023] [Accepted: 03/21/2023] [Indexed: 04/26/2023] Open
Abstract
Since dental pulp stem cells (DPSCs) were first reported, six types of dental SCs (DSCs) have been isolated and identified. DSCs originating from the craniofacial neural crest exhibit dental-like tissue differentiation potential and neuro-ectodermal features. As a member of DSCs, dental follicle SCs (DFSCs) are the only cell type obtained at the early developing stage of the tooth prior to eruption. Dental follicle tissue has the distinct advantage of large tissue volume compared with other dental tissues, which is a prerequisite for obtaining a sufficient number of cells to meet the needs of clinical applications. Furthermore, DFSCs exhibit a significantly higher cell proliferation rate, higher colony-formation capacity, and more primitive and better anti-inflammatory effects than other DSCs. In this respect, DFSCs have the potential to be of great clinical significance and translational value in oral and neurological diseases, with natural advantages based on their origin. Lastly, cryopreservation preserves the biological properties of DFSCs and enables them to be used as off-shelf products for clinical applications. This review summarizes and comments on the properties, application potential, and clinical transformation value of DFSCs, thereby inspiring novel perspectives in the future treatment of oral and neurological diseases.
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Affiliation(s)
- Chao Yang
- Research and Development Department, Shenzhen Uni-medica Technology Co., Ltd, Shenzhen 518051, Guangdong Province, China
- Department of Stomatology, The People’s Hospital of Longhua, Shenzhen 518109, Guangdong Province, China
| | - Xin-Ya Du
- Department of Stomatology, The People’s Hospital of Longhua, Shenzhen 518109, Guangdong Province, China
| | - Wen Luo
- Department of Stomatology, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China
- School of Stomatology, Hainan Medical University, Haikou 571199, Hainan Province, China
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9
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Wei X, Guo S, Liu Q, Liu L, Huo F, Wu Y, Tian W. Dental Follicle Stem Cells Promote Periodontal Regeneration through Periostin-Mediated Macrophage Infiltration and Reprogramming in an Inflammatory Microenvironment. Int J Mol Sci 2023; 24:ijms24076353. [PMID: 37047322 PMCID: PMC10094259 DOI: 10.3390/ijms24076353] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/18/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023] Open
Abstract
Dental follicle stem cells (DFSCs) have been verified to promote periodontal regeneration in an inflammatory microenvironment. When coping with inflammatory stimulation, DFSCs highly express periostin, a bioactive molecule closely related to periodontal homeostasis. It is worth exploring whether and how periostin plays a role in the promotion of periodontal regeneration by DFSCs. By tracking the fate of DFSCs, it was found that DFSCs significantly contributed to periodontal regeneration in rat periodontal defects while they had a low survival rate. They highly expressed periostin and improved the immune microenvironment in the defect area, especially via the recruitment and reprogramming of macrophages. Silencing periostin attenuated the effects of DFSCs in promoting periodontal regeneration and regulating macrophages. Recombinant human periostin (rhPeriostin) could not only directly promote macrophage reprogramming through the integrin αM/phosphorylated extracellular signal-regulated kinase (p-Erk)/Erk signaling pathway, but it also exhibited the potential to promote periodontal regeneration in rats when loaded in a collagen matrix. These results indicated that periostin is actively involved in the process by which DFSCs promote periodontal regeneration through the regulation of macrophages and is a promising molecular agent to promote periodontal regeneration. This study provides new insight into the mechanism by which DFSCs promote periodontal regeneration and suggests a new approach for periodontal regeneration therapy.
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Affiliation(s)
- Xiuqun Wei
- State Key Laboratory of Oral Diseases, & National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Shujuan Guo
- State Key Laboratory of Oral Diseases, & National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Qian Liu
- State Key Laboratory of Oral Diseases, & National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Li Liu
- State Key Laboratory of Oral Diseases, & National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Fangjun Huo
- State Key Laboratory of Oral Diseases, & National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu 610041, China
| | - Yafei Wu
- State Key Laboratory of Oral Diseases, & National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Correspondence: (Y.W.); (W.T.)
| | - Weidong Tian
- State Key Laboratory of Oral Diseases, & National Clinical Research Center for Oral Diseases, & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Correspondence: (Y.W.); (W.T.)
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10
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Regeneration of periodontal bone defects with mesenchymal stem cells in animal models. Systematic review and meta-analysis. Odontology 2023; 111:105-122. [PMID: 35788845 PMCID: PMC9810679 DOI: 10.1007/s10266-022-00725-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 06/08/2022] [Indexed: 01/07/2023]
Abstract
The aim of this study was to evaluate the efficacy of mesenchymal stem cells (MSCs) in the regeneration of periodontal bone defects in animal models. A systematic review and meta-analysis were conducted following the PRISMA guidelines, and the study was recorded in PROSPERO under reference number CDR42021247462. The PICO question was: is periodontal regeneration (cementum, periodontal ligament and alveolar bone) with MSCs more effective than other techniques? Three groups were considered: Group 1: MSCs alone or mixed with regenerative materials. Group 2: only regenerative materials. Group 3: no regenerative material nor MSCs. The search was conducted using MeSH with a total of 18 articles for qualitative analysis and 5 for quantitative analysis. For the meta-analysis, a modification of the effect size algorithm was developed, which considered a comparison of means between treatments using the Student's t sample distribution. When comparing the effect size between Group 1 and Group 2, the effect size for the new cementum was 2.83 mm with an estimated confidence interval of 95% (CI 95%) between 0.48 and 5.17 mm. When considering the fit to a random-effects model, the combined variance (τ2) was 6.1573 mm, with a standard deviation (SD) of 5.6008 mm and a percentage of total heterogeneity I2 of 92.33% (p < 0.0001). For new bone, the effect size was 0.88 mm, CI 95% - 0.25 to 2.01 mm, τ2 = 1.3108 mm (SD = 1.2021 mm) and I2 = 80.46%, p = 0.0004). With regard to the new periodontal ligament, it was not possible for the meta-analysis to be performed. MSCs have a greater capacity for tissue regeneration in root cementum than in alveolar bone compared to other regenerative materials.
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11
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Takedachi M, Kawasaki K, Sawada K, Sakura K, Murata M, Shimomura J, Kawakami K, Morimoto C, Miki K, Takeshita N, Iwayama T, Okura H, Matsuyama A, Saito M, Kitamura M, Murakami S. Periodontal Tissue Regeneration by Transplantation of Autologous Adipose Tissue-Derived Multi-Lineage Progenitor Cells With Carbonate Apatite. Cell Transplant 2023; 32:9636897231198296. [PMID: 37710973 PMCID: PMC10503283 DOI: 10.1177/09636897231198296] [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: 03/27/2023] [Revised: 08/09/2023] [Accepted: 08/15/2023] [Indexed: 09/16/2023] Open
Abstract
We have developed an autologous transplantation method using adipose tissue-derived multi-lineage progenitor cells (ADMPCs) as a method of periodontal tissue regeneration that can be adapted to severe periodontal disease. Our previous clinical study confirmed the safety of autologous transplantation of ADMPCs and demonstrated its usefulness in the treatment of severe periodontal disease. However, in the same clinical study, we found that the fibrin gel used as the scaffold material might have caused gingival recession and impaired tissue regeneration in some patients. Carbonate apatite has a high space-making capacity and has been approved in Japan for periodontal tissue regeneration. In this study, we selected carbonate apatite as a candidate scaffold material for ADMPCs and conducted an in vitro examination of its effect on the cellular function of ADMPCs. We further performed autologous ADMPC transplantation with carbonate apatite as the scaffold material in a model of one-wall bone defects in beagles and then analyzed the effect on periodontal tissue regeneration. The findings showed that carbonate apatite did not affect the cell morphology of ADMPCs and that it promoted proliferation. Moreover, no effect on secretor factor transcription was found. The results of the in vivo analysis confirmed the space-making capacity of carbonate apatite, and the acquisition of significant new attachment was observed in the group involving ADMPC transplantation with carbonate apatite compared with the group involving carbonate apatite application alone. Our results demonstrate the usefulness of carbonate apatite as a scaffold material for ADMPC transplantation.
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Affiliation(s)
- Masahide Takedachi
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Kohsuke Kawasaki
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Keigo Sawada
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Kazuma Sakura
- Department of Medical Innovation, Osaka University Hospital, Suita, Japan
| | - Mari Murata
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Junpei Shimomura
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Kazuma Kawakami
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Chiaki Morimoto
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Koji Miki
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Noboru Takeshita
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Tomoaki Iwayama
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Hanayuki Okura
- Center for Reverse Translational Research, Osaka Habikino Medical Center, Osaka Prefectural Hospital Organization, Habikino, Japan
- Adipo Medical Technology, Osaka, Japan
- Institute of Innovative Medical Technology, Osaka. Japan
| | - Akifumi Matsuyama
- Center for Reverse Translational Research, Osaka Habikino Medical Center, Osaka Prefectural Hospital Organization, Habikino, Japan
| | - Masahiro Saito
- Department of Restorative Dentistry, Division of Operative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Masahiro Kitamura
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Shinya Murakami
- Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Japan
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12
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Amato M, Santonocito S, Viglianisi G, Tatullo M, Isola G. Impact of Oral Mesenchymal Stem Cells Applications as a Promising Therapeutic Target in the Therapy of Periodontal Disease. Int J Mol Sci 2022; 23:13419. [PMID: 36362206 PMCID: PMC9658889 DOI: 10.3390/ijms232113419] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/26/2022] [Accepted: 10/31/2022] [Indexed: 11/06/2022] Open
Abstract
Periodontal disease is a chronic inflammatory condition affecting about 20-50% of people, worldwide, and manifesting clinically through the detection of gingival inflammation, clinical attachment loss, radiographically assessed resorption of alveolar bone, gingival bleeding upon probing, teeth mobility and their potential loss at advanced stages. It is characterized by a multifactorial etiology, including an imbalance of the oral microbiota, mechanical stress and systemic diseases such as diabetes mellitus. The current standard treatments for periodontitis include eliminating the microbial pathogens and applying biomaterials to treat the bone defects. However, periodontal tissue regeneration via a process consistent with the natural tissue formation process has not yet been achieved. Developmental biology studies state that periodontal tissue is composed of neural crest-derived ectomesenchyme. The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing the relevant literature that assesses the periodontal-regenerative potential of stem cells.
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Affiliation(s)
- Mariacristina Amato
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Simona Santonocito
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Gaia Viglianisi
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Marco Tatullo
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, 70122 Bari, Italy
| | - Gaetano Isola
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
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13
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Iwayama T, Sakashita H, Takedachi M, Murakami S. Periodontal tissue stem cells and mesenchymal stem cells in the periodontal ligament. JAPANESE DENTAL SCIENCE REVIEW 2022; 58:172-178. [PMID: 35607404 PMCID: PMC9123259 DOI: 10.1016/j.jdsr.2022.04.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/21/2022] [Accepted: 04/26/2022] [Indexed: 12/24/2022] Open
Abstract
Periodontal tissue stem cells, which play a crucial role in maintaining the homeostasis of periodontal tissues, are found in the periodontal ligament (PDL). These cells have long been referred to as mesenchymal stem/stromal cells (MSCs), and their clinical applications have been extensively studied. However, tissue stem cells in the PDL have not been thoroughly investigated, and they may be different from MSCs. Recent advances in stem cell biology, such as genetic lineage tracing, identification of label-retaining cells, and single-cell transcriptome analysis, have made it possible to analyze tissue stem cells in the PDL in vivo. In this review, we summarize recent findings on these stem cell populations in PDL and discuss future research directions toward developing periodontal regenerative therapy.
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14
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Yang K, Li S, Wang T, Yan X, He Q, Ning R, Xu X, Yao W, Zhang X, Yang C, Jiang M, Deng L. Development of an Orally Active Small-Molecule Inhibitor of Receptor Activator of Nuclear Factor-κB Ligand. J Med Chem 2022; 65:10992-11009. [PMID: 35960655 DOI: 10.1021/acs.jmedchem.2c00081] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Receptor activator of nuclear factor-κB (RANK) and its ligand, RANKL, play pivotal roles in bone remodeling. The monoclonal antibody denosumab successfully inhibited the maturation of osteoclasts (OCs) by binding to RANKL in the clinic. We continued our efforts to develop small-molecule inhibitors of RANKL. In this work, 41 β-carboline derivatives were synthesized based on previously synthesized compound Y1599 to improve its drug-like properties. Compound Y1693 was identified as a potent RANKL inhibitor that improved absorption-distribution-metabolism-excretion properties and effectively prevented RANKL-induced osteoclastogenesis and bone resorption. Furthermore, Y1693 also suppressed the expression of OC marker genes. Moreover, Y1693 demonstrated good tolerability and efficacy in an orally administered mouse model of osteoporosis as well as the ability to rescue alveolar bone loss in vivo caused by periodontal disease. Collectively, the above findings may provide a valuable direction for the development of novel antiresorptive therapies that target RANKL.
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Affiliation(s)
- Kai Yang
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China
| | - Shunyao Li
- State Key Laboratory of Drug Research, Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China
| | - Tianqi Wang
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China
| | - Xueming Yan
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China
| | - Qian He
- State Key Laboratory of Drug Research, Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China
| | - Ruonan Ning
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China
| | - Xing Xu
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China
| | - Wei Yao
- Center for Musculoskeletal Health, Department of Internal Medicine, The University of California at Davis Medical Center, Sacramento, California 95817, United States
| | - Xiaofei Zhang
- State Key Laboratory of Drug Research, Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China
| | - Chunhao Yang
- State Key Laboratory of Drug Research, Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China
| | - Min Jiang
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China
| | - Lianfu Deng
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China
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15
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ZHANG YUHAO, ZHAO WENHENG, JIA LIYANG, XU NAN, XIAO YAN, LI QIYAN. THE APPLICATION OF STEM CELLS IN TISSUE ENGINEERING FOR THE REGENERATION OF PERIODONTAL DEFECTS IN RANDOMIZED CONTROLLED TRIAL: A SYSTEMATIC REVIEW AND META-ANALYSIS. J Evid Based Dent Pract 2022; 22:101713. [DOI: 10.1016/j.jebdp.2022.101713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 01/26/2022] [Accepted: 02/11/2022] [Indexed: 11/26/2022]
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16
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Periodontal tissue regeneration by transplantation of autologous adipose tissue-derived multi-lineage progenitor cells. Sci Rep 2022; 12:8126. [PMID: 35581234 PMCID: PMC9114023 DOI: 10.1038/s41598-022-11986-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 04/12/2022] [Indexed: 12/04/2022] Open
Abstract
Periodontitis is a chronic inflammatory disease that destroys tooth-supporting periodontal tissue. Current periodontal regenerative therapies have unsatisfactory efficacy; therefore, periodontal tissue engineering might be established by developing new cell-based therapies. In this study, we evaluated the safety and efficacy of adipose tissue-derived multi-lineage progenitor cells (ADMPC) autologous transplantation for periodontal tissue regeneration in humans. We conducted an open-label, single-arm exploratory phase I clinical study in which 12 periodontitis patients were transplanted with autologous ADMPCs isolated from subcutaneous adipose tissue. Each patient underwent flap surgery during which autologous ADMPCs were transplanted into the bone defect with a fibrin carrier material. Up to 36 weeks after transplantation, we performed a variety of clinical examinations including periodontal tissue inspection and standardized dental radiographic analysis. A 36-week follow-up demonstrated no severe transplantation-related adverse events in any cases. ADMPC transplantation reduced the probing pocket depth, improved the clinical attachment level, and induced neogenesis of alveolar bone. Therapeutic efficiency was observed in 2- or 3-walled vertical bone defects as well as more severe periodontal bone defects. These results suggest that autologous ADMPC transplantation might be an applicable therapy for severe periodontitis by inducing periodontal regeneration.
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17
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Novello S, Tricot-Doleux S, Novella A, Pellen-Mussi P, Jeanne S. Influence of Periodontal Ligament Stem Cell-Derived Conditioned Medium on Osteoblasts. Pharmaceutics 2022; 14:pharmaceutics14040729. [PMID: 35456563 PMCID: PMC9028528 DOI: 10.3390/pharmaceutics14040729] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 03/24/2022] [Accepted: 03/25/2022] [Indexed: 02/04/2023] Open
Abstract
Mesenchymal stem cells (MSC) are involved in the regeneration of various missing or compromised periodontal tissues, including bone. MSC-derived conditioned medium (CM) has recently been explored as a favorable surrogate for stem cell therapy, as it is capable of producing comparable therapeutic effects. This study aimed to evaluate the influence of periodontal ligament stem cells (PDLSC)-CM on osteoblasts (OB) and its potential as a therapeutic tool for periodontal regeneration. Human PDLSC were isolated and characterized, and CM from these cells was collected. The presence of exosomes in the culture supernatant was observed by immunofluorescence and by transmission electron microscopy. CM was added to a cultured osteoblastic cell line (Saos-2 cells) and viability (MTT assay) and gene expression analysis (real-time PCR) were examined. A cell line derived from the periodontal ligament and showing all the characteristics of MSC was successfully isolated and characterized. The addition of PDLSC-CM to Saos-2 cells led to an enhancement of their proliferation and an increased expression of some osteoblastic differentiation markers, but this differentiation was not complete. Saos-2 cells were involved in the initial inflammation process by releasing IL-6 and activating COX2. The effects of PDLSC-CM on Saos-2 appear to arise from a cumulative effect of different effective components rather than a few factors present at high levels.
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Affiliation(s)
- Solen Novello
- ISCR (Institut des Sciences Chimiques de Rennes)—UMR 6226, Université de Rennes, 35000 Rennes, France; (S.T.-D.); (A.N.); (P.P.-M.); (S.J.)
- Unité de Formation et de Recherche d’Odontologie, Université de Rennes, 35000 Rennes, France
- UF Parodontologie, Pôle d’Odontologie, Centre Hospitalier Universitaire de Rennes, 35000 Rennes, France
- Correspondence:
| | - Sylvie Tricot-Doleux
- ISCR (Institut des Sciences Chimiques de Rennes)—UMR 6226, Université de Rennes, 35000 Rennes, France; (S.T.-D.); (A.N.); (P.P.-M.); (S.J.)
| | - Agnès Novella
- ISCR (Institut des Sciences Chimiques de Rennes)—UMR 6226, Université de Rennes, 35000 Rennes, France; (S.T.-D.); (A.N.); (P.P.-M.); (S.J.)
| | - Pascal Pellen-Mussi
- ISCR (Institut des Sciences Chimiques de Rennes)—UMR 6226, Université de Rennes, 35000 Rennes, France; (S.T.-D.); (A.N.); (P.P.-M.); (S.J.)
| | - Sylvie Jeanne
- ISCR (Institut des Sciences Chimiques de Rennes)—UMR 6226, Université de Rennes, 35000 Rennes, France; (S.T.-D.); (A.N.); (P.P.-M.); (S.J.)
- Unité de Formation et de Recherche d’Odontologie, Université de Rennes, 35000 Rennes, France
- UF Parodontologie, Pôle d’Odontologie, Centre Hospitalier Universitaire de Rennes, 35000 Rennes, France
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18
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Kebria MM, Milan PB, Peyravian N, Kiani J, Khatibi S, Mozafari M. Stem cell therapy for COVID-19 pneumonia. MOLECULAR BIOMEDICINE 2022; 3:6. [PMID: 35174448 PMCID: PMC8850486 DOI: 10.1186/s43556-021-00067-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 12/22/2021] [Indexed: 12/11/2022] Open
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus is a highly contagious microorganism, and despite substantial investigation, no progress has been achieved in treating post-COVID complications. However, the virus has made various mutations and has spread around the world. Researchers have tried different treatments to reduce the side effects of the COVID-19 symptoms. One of the most common and effective treatments now used is steroid therapy to reduce the complications of this disease. Long-term steroid therapy for chronic inflammation following COVID-19 is harmful and increases the risk of secondary infection, and effective treatment remains challenging owing to fibrosis and severe inflammation and infection. Sometimes our immune system can severely damage ourselves in disease. In the past, many researchers have conducted various studies on the immunomodulatory properties of stem cells. This property of stem cells led them to modulate the immune system of autoimmune diseases like diabetes, multiple sclerosis, and Parkinson's. Because of their immunomodulatory properties, stem cell-based therapy employing mesenchymal or hematopoietic stem cells may be a viable alternative treatment option in some patients. By priming the immune system and providing cytokines, chemokines, and growth factors, stem cells can be employed to build a long-term regenerative and protective response. This review addresses the latest trends and rapid progress in stem cell treatment for Acute Respiratory Distress Syndrome (ARDS) following COVID-19.
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Affiliation(s)
- Maziar Malekzadeh Kebria
- Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Peiman Brouki Milan
- Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Noshad Peyravian
- Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Jafar Kiani
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Present Address: Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Soheil Khatibi
- Babol University of Medical Sciences, Infection Diseases Centre, Mazandaran, Iran
| | - Masoud Mozafari
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
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19
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Iwasaki K, Peng Y, Kanda R, Umeda M, Ishikawa I. Stem Cell Transplantation and Cell-Free Treatment for Periodontal Regeneration. Int J Mol Sci 2022; 23:ijms23031011. [PMID: 35162935 PMCID: PMC8835344 DOI: 10.3390/ijms23031011] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/12/2022] [Accepted: 01/13/2022] [Indexed: 02/04/2023] Open
Abstract
Increasing attention has been paid to cell-based medicines. Many in vivo and in vitro studies have demonstrated the efficacy of stem cell transplantation for the regeneration of periodontal tissues over the past 20 years. Although positive evidence has accumulated regarding periodontal regeneration using stem cells, the exact mechanism of tissue regeneration is still largely unknown. This review outlines the practicality and emerging problems of stem cell transplantation therapy for periodontal regeneration. In addition, possible solutions to these problems and cell-free treatment are discussed.
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Affiliation(s)
- Kengo Iwasaki
- Institute of Dental Research, Osaka Dental University, Osaka 573-1121, Japan;
- Correspondence: ; Tel.: +81-72-864-3125
| | - Yihao Peng
- Department of Periodontology, Osaka Dental University, Osaka 573-1121, Japan; (Y.P.); (M.U.)
| | - Ryuhei Kanda
- Institute of Dental Research, Osaka Dental University, Osaka 573-1121, Japan;
| | - Makoto Umeda
- Department of Periodontology, Osaka Dental University, Osaka 573-1121, Japan; (Y.P.); (M.U.)
| | - Isao Ishikawa
- Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo 162-8666, Japan;
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20
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Garna DF, Hughes FJ, Ghuman MS. Regulation of gingival fibroblast phenotype by periodontal ligament cells in vitro. J Periodontal Res 2022; 57:402-411. [PMID: 35037259 PMCID: PMC9302626 DOI: 10.1111/jre.12971] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Accepted: 01/05/2022] [Indexed: 11/29/2022]
Abstract
Objectives Stem cell transplantation has shown modest effects on periodontal tissue regeneration, and it is still unclear how regenerative effects utilizing this modality are mediated. A greater understanding of the basic interactions between implanted and host cells is needed to improve future strategies. The aims of this study were to investigate the effects of periodontal ligament (PDL) cells on expression of periodontal markers and alkaline phosphatase (ALP) activity of gingival fibroblasts (GF). Materials and Methods Primary human PDL cells were co‐cultured with primary GF cultures either by direct co‐culture with subsequent FACS sorting or indirect co‐culture using transwell cultures and PDL cell conditioned medium. Expression of periodontal markers, asporin, nestin, and periostin, was assessed by qPCR and immunofluorescence staining. Alkaline phosphatase (ALP) expression was assessed by qPCR, histochemical staining, and activity assessed by para‐nitrophenol enzymatic assay. Single cultures of PDL cells and GF were used as controls. The role of Wnt signaling on ALP activity was assessed via Dkk1‐mediated inhibition. Results PDL cells significantly upregulated expression of PDL markers in GF with both direct and indirect co‐culture methods when compared to controls (6.05 vs. 0.73 and 59.48 vs. 17.55 fold change of asporin expression). PDL/GF cell co‐cultures significantly increased ALP activity in GF when compared with single GF cultures. Similar results were obtained when using conditioned medium isolated from PDL cell cultures. Dkk1 caused dose‐dependent reduction in ALP activity of GF cultured in PDL cell conditioned medium. Conclusions PDL cells stimulate expression of periodontal markers and osteogenic capacity of gingival fibroblasts via paracrine signaling which can be partially inhibited with addition of the Wnt antagonist, Dkk1.Further studies are required to identify specific secreted factors responsible for this activity.
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Affiliation(s)
- Devy F Garna
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK.,Department of Periodontology, Faculty of Dentistry, Padjadjaran University, Bandung, Indonesia
| | - Francis J Hughes
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK
| | - Mandeep S Ghuman
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK
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21
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Costa CA, Deliberador TM, Abuna RPF, Rodrigues TL, Souza SLSD, Palioto DB. Mesenchymal stem cells surpass the capacity of bone marrow aspirate concentrate for periodontal regeneration. J Appl Oral Sci 2022; 30:e20210359. [PMID: 35384987 PMCID: PMC8983037 DOI: 10.1590/1678-7757-2021-0359] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 01/28/2022] [Indexed: 12/23/2022] Open
Abstract
Regenerative approaches using mesenchymal stem cells (MSCs) have been evaluated to promote the complete formation of all missing periodontal tissues, e.g., new cementum, bone, and functional periodontal ligaments. MSCs derived from bone marrow have been applied to bone and periodontal defects in several forms, including bone marrow aspirate concentrate (BMAC) and cultured and isolated bone marrow mesenchymal stem cells (BM-MSCs). This study aimed to evaluate the periodontal regeneration capacity of BMAC and cultured BM-MSCs in the wound healing of fenestration defects in rats. Methodology: BM-MSCs were obtained after bone marrow aspiration of the isogenic iliac crests of rats, followed by cultivation and isolation. Autogenous BMAC was collected and centrifuged immediately before surgery. In 36 rats, fenestration defects were created and treated with suspended BM-MSCs, BMAC or left to spontaneously heal (control) (N=6). Their regenerative potential was assessed by microcomputed tomography (µCT) and histomorphometry, as well as their cell phenotype and functionality by the Luminex assay at 15 and 30 postoperative days. Results: BMAC achieved higher bone volume in 30 days than spontaneous healing (p<0.0001) by enhancing osteoblastic lineage commitment maturation, with higher levels of osteopontin (p=0.0013). Defects filled with cultured BM-MSCs achieved higher mature bone formation in early stages than spontaneous healing and BMAC (p=0.0241 and p=0.0143, respectively). Moreover, significantly more cementum-like tissue formation (p<0.0001) was observed with new insertion of fibers in specimens treated with BM-MSCs within 30 days. Conclusion: Both forms of cell transport, BMAC and BM-MSCs, promoted bone formation. However, early bone formation and maturation were achieved when cultured BM-MSCs were used. Likewise, only cultured BM-MSCs were capable of achieving complete periodontal regeneration with inserted fibers in the new cementum-like tissue.
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Kouhestani F, Aghandeh P, Isamorad F, Akbari S, Tanbakuchi B, Motamedian S. Efficacy of Application of Periodontal Ligament Stem Cells in Bone Regeneration: A Systematic Review of Animal Studies. DENTAL HYPOTHESES 2022. [DOI: 10.4103/denthyp.denthyp_136_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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Abstract
In this review, the authors consider the substantial advances that have been made in recent years in stem cell-based periodontal regeneration. These advances involve identifying dental- and nondental-derived stem cells with the capacity to modulate periodontal regeneration, human clinical trials, and emerging concepts, including cell banking, good manufacturing processes, and overall clinical translation.
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Acute Skin Wounds Treated with Mesenchymal Stem Cells and Biopolymer Compositions Alone and in Combination: Evaluation of Agent Efficacy and Analysis of Healing Mechanisms. Pharmaceutics 2021; 13:pharmaceutics13101534. [PMID: 34683826 PMCID: PMC8537629 DOI: 10.3390/pharmaceutics13101534] [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] [Received: 08/12/2021] [Revised: 09/16/2021] [Accepted: 09/18/2021] [Indexed: 11/24/2022] Open
Abstract
We studied the efficacy of using mesenchymal stem cells (MSC) and a polymeric compound (based on chitosan and cellulose with integrated cerium dioxide nanoparticles (PCCD)) in wound healing, and to compare the effects with various invasive and external drugs used for the same purpose. Two wounds were made on the backs of each of 112 Wistar rats, removing the skin. Eight groups were studied: Control_0—intact wounds; Control_ss—0.9% NaCl injections; MSC injections; Control_msc—intact wounds on the opposite side of the body from the MSC group; external application of the PCCD; external application of a combination of the drugs PCCD + MSC; DCh –ointment Dioxomethyltetrahydropyrimidine + Chloramphenicol; and DHCB—injections of a deproteinized hemoderivative of calf blood. After 14 days, we evaluated the state and size of the wounds, studied the level of microcirculation, performed a histological study, and identified and counted the different types of cells. The most effective remedy was combination PCCD + MSC. The treatments in the PCCD and MSC groups were more effective than in the DHCB and DCh groups. Invasive drugs and DCh slowed the regeneration process. DHCB did not affect the rate of healing for acute wounds without ischemia during the first week. The proven efficacy of developed polymeric compounds demonstrates the feasibility of further studies in clinical practice.
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Oral Cavity as a Source of Mesenchymal Stem Cells Useful for Regenerative Medicine in Dentistry. Biomedicines 2021; 9:biomedicines9091085. [PMID: 34572271 PMCID: PMC8469189 DOI: 10.3390/biomedicines9091085] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 08/19/2021] [Accepted: 08/23/2021] [Indexed: 12/17/2022] Open
Abstract
The use of mesenchymal stem cells (MSCs) for regenerative purposes has become common in a large variety of diseases. In the dental and maxillofacial field, there are emerging clinical needs that could benefit from MSC-based therapeutic approaches. Even though MSCs can be isolated from different tissues, such as bone marrow, adipose tissue, etc., and are known for their multilineage differentiation, their different anatomical origin can affect the capability to differentiate into a specific tissue. For instance, MSCs isolated from the oral cavity might be more effective than adipose-derived stem cells (ASCs) for the treatment of dental defects. Indeed, in the oral cavity, there are different sources of MSCs that have been individually proposed as promising candidates for tissue engineering protocols. The therapeutic strategy based on MSCs can be direct, by using cells as components of the tissue to be regenerated, or indirect, aimed at delivering local growth factors, cytokines, and chemokines produced by the MSCs. Here, the authors outline the major sources of mesenchymal stem cells attainable from the oral cavity and discuss their possible usage in some of the most compelling therapeutic frontiers, such as periodontal disease and dental pulp regeneration.
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Local and Remote Effects of Mesenchymal Stem Cell Administration on Skin Wound Regeneration. PATHOPHYSIOLOGY 2021; 28:355-372. [PMID: 35366280 PMCID: PMC8830469 DOI: 10.3390/pathophysiology28030024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 08/10/2021] [Accepted: 08/10/2021] [Indexed: 12/14/2022] Open
Abstract
Wound healing is an important medical problem. We evaluated the efficacy of locally administered mesenchymal stem cells (MSCs) isolated from human umbilical cords on the dynamics of skin wound healing. The study was conducted on the backs of Wistar rats, where two square wounds were created by removing all layers of the skin. Four groups were studied in two series of experiments: (1) a Control_NaCl group (the wounds were injected with 0.9% NaCl solution) and a Control_0 group (intact wounds on the opposite side of the same rat's back); (2) an MSC group (injected MSCs, local effect) and a Control_sc group (intact wounds on the opposite side of the back, remote MSC effect). The area and temperature of the wounds and the microcirculation of the wound edges were measured. Histological and morphometric studies were performed on days 3 and 7 after the wounds were created. The results showed that the injection trauma (Control_NaCl) slowed the regeneration process. In both MSC groups (unlike in either control group), we observed no increase in the area of the wounds; in addition, we observed inhibition of the inflammatory process and improved wound regeneration on days 1-3 in the remote group and days 1-5 in the local (injected) group. The MSC and Control_sc groups demonstrated improved microcirculation and suppression of leukocyte infiltration on day 3. On day 7, all the studied parameters of the wounds of the Control_0 group were the same as those of the wounds that received cell therapy, although in contrast to the results of the Control_ NaCl group, fibroblast proliferation was greater in the MSC and Control_sc groups. The dynamics of the size of the wounds were comparable for both local and remote application of MSCs. Thus, even a one-time application of MSCs was effective during the first 3-5 days after injury due to anti-inflammatory processes, which improved the regeneration process. Remote application of MSC, as opposed to direct injection, is advisable, especially in the case of multiple wounds, since the results were indistinguishable between the groups and injection trauma was shown to slow healing.
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Apatzidou DA, Bakopoulou AA, Kouzi-Koliakou K, Karagiannis V, Konstantinidis A. A tissue-engineered biocomplex for periodontal reconstruction. A proof-of-principle randomized clinical study. J Clin Periodontol 2021; 48:1111-1125. [PMID: 33899259 DOI: 10.1111/jcpe.13474] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 04/05/2021] [Accepted: 04/11/2021] [Indexed: 12/14/2022]
Abstract
AIM To assess the safety/efficacy of a tissue-engineered biocomplex in periodontal reconstruction. METHODS Twenty-seven intrabony defects were block-randomized across three treatment groups: Group-A (NA = 9) received autologous clinical-grade alveolar bone marrow mesenchymal stem cells (a-BMMSCs), seeded into collagen scaffolds, enriched with autologous fibrin/platelet lysate (aFPL). In Group-B (NB = 10), the collagen scaffold/aFPL devoid of a-BMMSCs filled the osseous defect. Group-C (NC = 8) received Minimal Access Flap surgery retaining the soft tissue wall of defects identically with Groups-A/-B. Subjects were clinically/radiographically assessed before anaesthesia (baseline) and repeatedly over 12 months. RESULTS Quality controls were satisfied before biocomplex transplantation. There were no adverse healing events. All approaches led to significant clinical improvements (p < .001) with no inter-group differences. At 12 months, the estimated marginal means for all groups were as follows: 3.0 (95% CI: 1.9-4.1) mm for attachment gain; 3.7 (2.7-4.8) mm for probing pocket depth reduction; 0.7 (0.2-1.3) mm increase in recession. An overall greater mean reduction in the radiographic Cemento-Enamel Junction to Bottom Defect (CEJ-BD) distance was found for Groups-A/-C over Group-B (p < .023). CONCLUSION Radiographic evidence of bone fill was less pronounced in Group-B, although clinical improvements were similar across groups. All approaches aimed to trigger the innate healing potential of tissues. Cell-based therapy is justified for periodontal reconstruction and remains promising in selected cases.
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Affiliation(s)
- Danae A Apatzidou
- Department of Preventive Dentistry, Periodontology and Implant Biology, School of Dentistry, Faculty of Health Sciences (FHS), Aristotle University of Thessaloniki (AUTh), Thessaloniki, Greece
| | - Athina A Bakopoulou
- Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences (FHS), Aristotle University of Thessaloniki (AUTh), Thessaloniki, Greece
| | | | - Vassilis Karagiannis
- School of Mathematics, Aristotle University of Thessaloniki, AUTh, Thessaloniki, Greece
| | - Antonis Konstantinidis
- Department of Preventive Dentistry, Periodontology and Implant Biology, School of Dentistry, Faculty of Health Sciences (FHS), Aristotle University of Thessaloniki (AUTh), Thessaloniki, Greece
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Chew JRJ, Tan BL, Lu JX, Tong HJ, Duggal MS. Cell-Based Therapy for Tooth Replantation Following Avulsion: A Systematic Review. TISSUE ENGINEERING PART B-REVIEWS 2021; 28:351-363. [PMID: 33593127 DOI: 10.1089/ten.teb.2021.0016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The management of avulsed teeth undergoing delayed replantation remains a clinical challenge as there are currently no effective interventions that can improve periodontal healing and prevent replacement root resorption. While several preclinical studies have reported varied success using cell-based tissue engineering to improve periodontal healing, a consensus is required before further clinical translation. Therefore, this systematic review seeks to evaluate the efficacy of cell-based therapy in promoting periodontal healing following delayed replantation in animal models. MEDLINE (PubMed) and Embase were searched on September 27, 2020. Ten studies involving rodent and dog models met the inclusion criteria. Cell sources included gingiva, periodontal ligament (PDL), bone marrow, and adipose tissues. Generally, cell-based therapy had increased the proportion of root surfaces displaying periodontal healing and concomitantly reduced the proportion presenting with replacement root resorption and ankylosis. The best outcomes were observed following treatment with PDL-derived cells of various potency. Future preclinical studies will benefit from adopting measures to minimize bias during the conduct of animal experiments and the standardization of the outcome measures reporting. This will facilitate future reviews with possible pooling of results in the form of meta-analyses, allowing a consensus to be obtained from the literature. In addition, further research will be required to shed light on the implications of using allogeneic cells as well as the optimization of cell delivery protocols. The findings of this systematic review demonstrated the therapeutic potential of certain cell-based therapies in promoting periodontal healing following delayed replantation, thus highlighting their prospective clinical benefits and translational value.
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Affiliation(s)
- Jacob Ren Jie Chew
- Faculty of Dentistry, National University of Singapore, Singapore, Singapore
| | - Bing Liang Tan
- Faculty of Dentistry, National University of Singapore, Singapore, Singapore
| | - Jacinta Xiaotong Lu
- Faculty of Dentistry, National University of Singapore, Singapore, Singapore
| | - Huei Jinn Tong
- Faculty of Dentistry, National University of Singapore, Singapore, Singapore
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Sánchez N, Fierravanti L, Núñez J, Vignoletti F, González-Zamora M, Santamaría S, Suárez-Sancho S, Fernández-Santos ME, Figuero E, Herrera D, García-Sanz JA, Sanz M. Periodontal regeneration using a xenogeneic bone substitute seeded with autologous periodontal ligament-derived mesenchymal stem cells: A 12-month quasi-randomized controlled pilot clinical trial. J Clin Periodontol 2021; 47:1391-1402. [PMID: 32946590 DOI: 10.1111/jcpe.13368] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 08/25/2020] [Accepted: 09/05/2020] [Indexed: 12/20/2022]
Abstract
AIM To evaluate the safety and efficacy of autologous periodontal ligament-derived mesenchymal stem cells (PDL-MSCs) embedded in a xenogeneic bone substitute (XBS) for the regenerative treatment of intra-bony periodontal defects. MATERIAL AND METHODS This quasi-randomized controlled pilot phase II clinical trial included patients requiring a tooth extraction and presence of one intra-bony lesion (1-2 walls). Patients were allocated to either the experimental (XBS + 10 × 106 PDL-MSCs/100 mg) or the control group (XBS). Clinical and radiographical parameters were recorded at baseline, 6, 9 and 12 months. The presence of adverse events was also evaluated. Chi-square, Student's t test, Mann-Whitney U, repeated-measures ANOVA and regression models were used. RESULTS Twenty patients were included. No serious adverse events were reported. Patients in the experimental group (n = 9) showed greater clinical attachment level (CAL) gain (1.44, standard deviation [SD] = 1.87) and probing pocket depth (PPD) reduction (2.33, SD = 1.32) than the control group (n = 10; CAL gain = 0.88, SD = 1.68, and PPD reduction = 2.10, SD = 2.46), without statistically significant differences. CONCLUSION The application of PDL-MSCs to XBS for the treatment of one- to two-wall intra-bony lesions was safe and resulted in low postoperative morbidity and appropriate healing, although its additional benefit, when compared with the XBS alone, was not demonstrated.
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Affiliation(s)
- Nerea Sánchez
- ETEP (Etiology and Therapy of Periodontal and Peri-implant Diseases) Research Group, University Complutense, Madrid, Spain
| | - Ludovica Fierravanti
- ETEP (Etiology and Therapy of Periodontal and Peri-implant Diseases) Research Group, University Complutense, Madrid, Spain
| | - Javier Núñez
- ETEP (Etiology and Therapy of Periodontal and Peri-implant Diseases) Research Group, University Complutense, Madrid, Spain
| | - Fabio Vignoletti
- ETEP (Etiology and Therapy of Periodontal and Peri-implant Diseases) Research Group, University Complutense, Madrid, Spain
| | - María González-Zamora
- ETEP (Etiology and Therapy of Periodontal and Peri-implant Diseases) Research Group, University Complutense, Madrid, Spain
| | - Silvia Santamaría
- Margarita Salas Center for Biological Research (CIB-CSIC), Madrid, Spain
| | - Susana Suárez-Sancho
- GMP-Cell Production Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Red de Terapia Celular (TERCEL) and CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
| | - María Eugenia Fernández-Santos
- GMP-Cell Production Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Red de Terapia Celular (TERCEL) and CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
| | - Elena Figuero
- ETEP (Etiology and Therapy of Periodontal and Peri-implant Diseases) Research Group, University Complutense, Madrid, Spain
| | - David Herrera
- ETEP (Etiology and Therapy of Periodontal and Peri-implant Diseases) Research Group, University Complutense, Madrid, Spain
| | - Jose A García-Sanz
- Margarita Salas Center for Biological Research (CIB-CSIC), Madrid, Spain
| | - Mariano Sanz
- ETEP (Etiology and Therapy of Periodontal and Peri-implant Diseases) Research Group, University Complutense, Madrid, Spain
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Saha S, Chakrabarti S, Singh PK, Poddar J, Satapathi S, Saini S, Kakar SS, Roy P. Physiological Relevance of Angiotensin Converting Enzyme 2 As a Metabolic Linker and Therapeutic Implication of Mesenchymal Stem Cells in COVID-19 and Hypertension. Stem Cell Rev Rep 2021; 17:132-143. [PMID: 32748331 PMCID: PMC7397455 DOI: 10.1007/s12015-020-10012-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Severe acute respiratory syndrome corona virus - 2 (SARS-CoV-2) is a single stranded RNA virus and responsible for infecting human being. In many cases the individual may remain asymptomatic. Some recently reported studies revealed that individuals of elderly age group and with pre-existing medical conditions such as hypertension, diabetes mellitus had severe consequences, even may lead to death. However, it is not clearly delineated whether hypertension itself or associated comorbidities or antihypertensive therapy contributes to the grave prognosis of COVID-19 infections. This review is aimed to decipher the exact mechanisms involved at molecular level from existing evidence and as reported. It has been reported that SARS-CoV-2 enters into the host cell through interaction between conserved residues of viral spike protein and angiotensin converting enzyme 2 (ACE2) receptor which is highly expressed in host's cardiac and pulmonary cells and finally transmembrane protease, serine-2 (TMPRSS2), helps in priming of the surface protein. Subsequently, symptom related to multi organ involvement is primarily contributed by cytokine storm. Although various clinical trials are being conducted on renin- angiotensin- system inhibitor, till to date there is no standard treatment protocol approved for critically ill COVID-19 positive cases with pre-existing hypertension. Recently, several studies are carried out to document the safety and efficacy outcome of mesenchymal stem cell transplantation based on its immunomodulatory and regenerative properties. Therefore, identification of future novel therapeutics in the form of mesenchymal stem cell either alone or in combination with pharmacological approach could be recommended for combating SARS-CoV-2 which might be dreadful to debilitating elderly people. Graphical Abstract.
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Affiliation(s)
- Sarama Saha
- Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, India
| | - Sasanka Chakrabarti
- Department of Biochemistry and Central Research Cell, Maharishi Markandeshwar (deemed to be) University, Mullana, Haryana, India
| | - Praveen Kumar Singh
- Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, India
| | - Jit Poddar
- Department of Biochemistry and Central Research Cell, Maharishi Markandeshwar (deemed to be) University, Mullana, Haryana, India
| | - Soumitra Satapathi
- Department of Physics, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247 667, India
| | - Surendra Saini
- Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247 667, India
| | - Sham S Kakar
- Department of Physiology and James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40292, USA
| | - Partha Roy
- Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247 667, India.
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Zhang Y, Wang P, Wang Y, Li J, Qiao D, Chen R, Yang W, Yan F. Gold Nanoparticles Promote the Bone Regeneration of Periodontal Ligament Stem Cell Sheets Through Activation of Autophagy. Int J Nanomedicine 2021; 16:61-73. [PMID: 33442250 PMCID: PMC7797360 DOI: 10.2147/ijn.s282246] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 12/19/2020] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE Cell sheet technology (CST) is advantageous for repairing alveolar bone defects in clinical situations, and osteogenic induction before implantation may result in enhanced bone regeneration. Herein, we observed the effect of gold nanoparticles (AuNPs) on osteogenic differentiation of periodontal ligament stem cell (PDLSC) sheets and explored their potential mechanism of action. METHODS PDLSCs were cultured in cell sheet induction medium to obtain cell sheets. PDLSC sheets were treated with or without AuNPs. Alkaline phosphatase, alizarin red S, von Kossa, and immunofluorescence staining were used to observe the effects of AuNPs on the osteogenic differentiation of PDLSC sheets. Western blotting was performed to evaluate the osteogenic effects and autophagy activity. The cell sheets were transplanted into the dorsa of nude mice, and bone regeneration was analyzed by micro-CT and histological staining. RESULTS AuNPs could promote the osteogenic differentiation of PDLSC sheets by upregulating bone-related protein expression and mineralization. The 45-nm AuNPs were more effective than 13-nm AuNPs. Additional analysis demonstrated that their ability to promote differentiation could depend on activation of the autophagy pathway through upregulation of microtubule-associated protein light chain 3 and downregulation of sequestosome 1/p62. Furthermore, AuNPs significantly promoted the bone regeneration of PDLSC sheets in ectopic models. CONCLUSION AuNPs enhance the osteogenesis of PDLSC sheets by activating autophagy, and 45-nm AuNPs were more effective than 13-nm AuNPs. This study may provide an AuNP-based pretreatment strategy for improving the application of CST in bone repair and regeneration.
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Affiliation(s)
- Yangheng Zhang
- Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China
| | - Peng Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China
| | - Yuxian Wang
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu, People’s Republic of China
| | - Jiao Li
- Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China
| | - Dan Qiao
- Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China
| | - Rixin Chen
- Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China
| | - Wenrong Yang
- School of Life and Environmental Science, Centre for Chemistry and Biotechnology, Deakin University, Geelong, VIC, Australia
| | - Fuhua Yan
- Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China
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Bakopoulou A. Prospects of Advanced Therapy Medicinal Products-Based Therapies in Regenerative Dentistry: Current Status, Comparison with Global Trends in Medicine, and Future Perspectives. J Endod 2020; 46:S175-S188. [PMID: 32950189 DOI: 10.1016/j.joen.2020.06.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
INTRODUCTION Regenerative medicine offers innovative approaches to restore damaged tissues on the basis of tissue engineering (TE). Although research on advanced therapy medicinal products (ATMPs) has been very active in recent years, the number of licensed products remains surprisingly low and restricted to the treatment of severe, incurable diseases. METHODS This paper provides a critical review of current literature on the regulatory, clinical, and commercial status of ATMP-based therapies in the EU and worldwide and the hurdles to overcome for their broader application in Regenerative Dentistry. RESULTS Competent authorities have focused on developing regulatory pathways to address unmet patient needs. Oncology represents the dominating field, followed by cardiovascular, musculoskeletal, neurodegenerative, immunologic, and inherited diseases. Yet, the status remains in early development, and scientific, regulatory, and cost-effectiveness issues impose considerable hurdles toward marketing authorization, technology adoption, and patient accessibility. In this context, although regenerative dentistry has achieved breakthrough innovations in TE of several dental/oral tissues in preclinical models, it has hardly harnessed research progress to integrate innovative regenerative treatments into clinical practice. CONCLUSION Global demographic changes, which demonstrate a steady increase of the aging population, highlight the societal need for the application of ATMP-based therapies in the treatment of noncommunicable diseases (NCDs). Although oral diseases, as an integral part of NCDs, are not life-threatening and largely preventable, they sustain high prevalence, with severe burden on economy and quality of life. In this perspective, the urgent request to ultimately translate draining research in dental TE conducted during the last decades into innovative treatments brought safely and cost-effectively into society at large still holds the stage. This review provides an overview of the regulatory, clinical, and commercial status of ATMP-based therapies in the European Union and worldwide and the hurdles to overcome for their broader application in regenerative dentistry.
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Affiliation(s)
- Athina Bakopoulou
- Faculty of Health Sciences, Department of Prosthodontics, School of Dentistry, Aristotle University of Thessaloniki (AUTH), Thessaloniki, Greece.
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Xu XY, Tian BM, Xia Y, Xia YL, Li X, Zhou H, Tan YZ, Chen FM. Exosomes derived from P2X7 receptor gene-modified cells rescue inflammation-compromised periodontal ligament stem cells from dysfunction. Stem Cells Transl Med 2020; 9:1414-1430. [PMID: 32597574 PMCID: PMC7581448 DOI: 10.1002/sctm.19-0418] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 04/24/2020] [Accepted: 05/30/2020] [Indexed: 12/17/2022] Open
Abstract
Although cellular therapy has been proposed for inflammation‐related disorders such as periodontitis for decades, clinical application has been unsuccessful. One explanation for these disappointing results is that the functions of stem cells are substantially compromised when they are transplanted into an inflammatory in vivo milieu. Considering the previous finding that P2X7 receptor (P2X7R) gene modification is able to reverse inflammation‐mediated impairment of periodontal ligament stem cells (PDLSCs), we further hypothesized that cells subjected to P2X7R gene transduction also exert influences on other cells within an in vivo milieu via an exosome‐mediated paracrine mechanism. To define the paracrine ability of P2X7R gene‐modified cells, P2X7R gene‐modified stem cell‐derived conditional medium (CM‐Ad‐P2X7) and exosomes (Exs‐Ad‐P2X7) were used to incubate PDLSCs. In an inflammatory osteogenic microenvironment, inflammation‐mediated changes in PDLSCs were substantially reduced, as shown by quantitative real‐time PCR (qRT‐PCR) analysis, Western blot analysis, alkaline phosphatase (ALP) staining/activity assays, and Alizarin red staining. In addition, the Agilent miRNA microarray system combined with qRT‐PCR analysis revealed that miR‐3679‐5p, miR‐6515‐5p, and miR‐6747‐5p were highly expressed in Exs‐Ad‐P2X7. Further functional tests and luciferase reporter assays revealed that miR‐3679‐5p and miR‐6747‐5p bound directly to the GREM‐1 protein, while miR‐6515‐5p bound to the GREM‐1 protein indirectly; these effects combined to rescue inflammation‐compromised PDLSCs from dysfunction. Thus, in addition to maintaining their robust functionality under inflammatory conditions, P2X7R gene‐modified stem cells may exert positive influences on their neighbors via a paracrine mechanism, pointing to a novel strategy for modifying the harsh local microenvironment to accommodate stem cells and promote improved tissue regeneration.
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Affiliation(s)
- Xin-Yue Xu
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China.,Shaanxi Key Laboratory of Free Radical Biology and Medicine, The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Fourth Military Medical University, Xi'an, People's Republic of China
| | - Bei-Min Tian
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China
| | - Yu Xia
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China
| | - Yun-Long Xia
- Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China
| | - Xuan Li
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China.,Shaanxi Key Laboratory of Free Radical Biology and Medicine, The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Fourth Military Medical University, Xi'an, People's Republic of China
| | - Huan Zhou
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China.,Shaanxi Key Laboratory of Free Radical Biology and Medicine, The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Fourth Military Medical University, Xi'an, People's Republic of China
| | - Yi-Zhou Tan
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China
| | - Fa-Ming Chen
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China
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34
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Abstract
"COVID-19" is the word that certainly isn't forgotten by everybody who lives in the first half of the twenty-first century. COVID-19, as a pandemic, has led many researchers from different biomedical fields to find solutions or treatments to manage the pandemic. However, no standard treatment for this disease has been discovered to date. Probably, preventing the severe acute respiratory infection form of COVID-19 as the most dangerous phase of this disease can be helpful for the treatment and reduction of the death rate. In this regard, mesenchymal stem cells (MSCs)-based immunomodulation treatment has been proposed as a suitable therapeutic approach and several clinical trials have begun. Recently, MSCs according to their immunomodulatory and regenerative properties attract attention in clinical trials. After the intravenous transplantation of MSCs, a significant population of cells accumulates in the lung, which they alongside immunomodulatory effect could protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction. Given the uncertainties in this area, we reviewed reported clinical trials and hypotheses to provide useful information to researchers and those interested in stem cell therapy. In this study, we considered this new approach to improve patient's immunological responses to COVID-19 using MSCs and discussed the aspects of this proposed treatment. However, currently, there are no approved MSC-based approaches for the prevention and/or treatment of COVID-19 patients but clinical trials ongoing.
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Affiliation(s)
- Ali Golchin
- Department of Clinical Biochemistry and Applied Cell Science, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
| | - Ehsan Seyedjafari
- Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
| | - Abdolreza Ardeshirylajimi
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- SinaCell Research and Product Center, Tehran, Iran.
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