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Ponnaiyan D, Rughwani RR, Victor DJ, Shetty G. Stem Cells in the Periodontium-Anatomically Related Yet Physiologically Diverse. Eur J Dent 2024; 18:1-13. [PMID: 36588293 PMCID: PMC10959637 DOI: 10.1055/s-0042-1759487] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Periodontitis is a complex chronic disease discernible by the deterioration of periodontal tissue. The goal of periodontal therapy is to achieve complete tissue regeneration, and one of the most promising treatment options is to harness the regenerative potential of stem cells available within the periodontal complex. Periodontal ligament stem cells, gingival mesenchymal stem cells, oral periosteal stem cells, and dental follicle stem cells have structural similarities, but their immunological responses and features differ. The qualities of diverse periodontal stem cells, their immune-modulatory effects, and variances in their phenotypes and characteristics will be discussed in this review. Although there is evidence on each stem cell population in the periodontium, understanding the differences in markers expressed, the various research conducted so far on their regenerative potential, will help in understanding which stem cell population will be a better candidate for tissue engineering. The possibility of selecting the most amenable stem cell population for optimal periodontal regeneration and the development and current application of superior tissue engineering treatment options such as autologous transplantation, three-dimensional bioengineered scaffolds, dental stem cell-derived extracellular vesicles will be explored.
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Affiliation(s)
- Deepa Ponnaiyan
- Department of Periodontics and Oral Implantology, SRM Dental College and Hospital, Ramapuram, Chennai, Tamil Nadu, India
| | - Roshan R. Rughwani
- Department of Periodontics and Oral Implantology, SRM Dental College and Hospital, Ramapuram, Chennai, Tamil Nadu, India
| | - Dhayanand John Victor
- Department of Periodontics and Oral Implantology, SRM Dental College and Hospital, Ramapuram, Chennai, Tamil Nadu, India
| | - Ganesh Shetty
- Dental and Orthodontic Clinic, Bangalore, Karnataka, India
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Nugraha AP, Ramadhani NF, Riawan W, Ihsan IS, Ernawati DS, Ridwan RD, Narmada IB, Saskianti T, Rezkita F, Sarasati A, Noor TNEBTA, Inayatillah B, Nugraha AP, Joestandari F. Gingival Mesenchymal Stem Cells Metabolite Decreasing TRAP, NFATc1, and Sclerostin Expression in LPS-Associated Inflammatory Osteolysis In Vivo. Eur J Dent 2023; 17:881-888. [PMID: 35728613 PMCID: PMC10569879 DOI: 10.1055/s-0042-1748529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
OBJECTIVE Bone is a dynamic tissue that undergoes remodeling. During bone remodeling, there are transcription factors such as nuclear factor-activated T cells-1 (NFATc1), sclerostin, and tartrate-resistant acid phosphatase (TRAP) that are released for bone resorption. Metabolite from gingival mesenchymal stem cells (GMSCs) has the ability to activate proliferation, migration, immunomodulation, and tissue regeneration of bone cells and tissues. Furthermore, the aim of this study is to investigate the metabolite of GMSCs' effect on expression of NFATc1, TRAP, and sclerostin in calvaria bone resorption of Wistar rats. MATERIALS AND METHODS Twenty male healthy Wistar rats (Rattus norvegicus), 1 to 2 months old, 250 to 300 g body were divided into four groups, namely group 1 (G1): 100 µg phosphate-buffered saline day 1 to 7; group 2 (G2): 100 μg lipopolysaccharide (LPS) day 1 to 7; group 3 (G3): 100 μg LPS + 100 μg GMSCs metabolite day 1 to 7; and group 4 (G4): 100 μg GMSCs metabolite day 1 to 7. Escherichia coli LPS was used to induce inflammatory osteolysis on the calvaria with subcutaneous injection. GMSCs metabolite was collected after passage 4 to 5, then injected subcutaneously on the calvaria. All samples were sacrificed on the day 8 through cervical dislocation. The expression of TRAP, NFATc1, and sclerostin of osteoclast in the calvaria was observed with 1,000× magnification. STATISTICAL ANALYSIS One-way analysis of variance and Tukey honest significant different were conducted to analyze differences between groups (p < 0.05). RESULTS The administration of GMSCs metabolite can significantly decrease TRAP, NFATc1, and sclerostin expression (p < 0.05) in LPS-associated inflammatory osteolysis calvaria in Wistar rats (R. norvegicus). There were significantly different TRAP, NFATc1, and sclerostin expressions between groups (p < 0.05). CONCLUSION GMSCs metabolite decrease TRAP, NFATc1, and sclerostin expression in LPS-associated osteolysis calvaria in Wistar rats (R. norvegicus) as documented immunohistochemically.
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Affiliation(s)
- Alexander Patera Nugraha
- Dental Regenerative Research Group, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Nastiti Faradilla Ramadhani
- Dental Regenerative Research Group, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Dentomaxillofacial Radiology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Wibi Riawan
- Department of Biomolecular Biochemistry, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
| | - Igo Syaiful Ihsan
- Stem Cell Research and Development Center, Universitas Airlangga Surabaya, Surabaya, Indonesia
| | - Diah Savitri Ernawati
- Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Rini Devijanti Ridwan
- Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Ida Bagus Narmada
- Dental Regenerative Research Group, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Tania Saskianti
- Department of Pediatric Dentistry, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Fianza Rezkita
- Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Andari Sarasati
- Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
| | | | - Bilqis Inayatillah
- Department of Basic Medical of Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
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Li H, Gu J, Sun X, Zuo Q, Li B, Gu X. Isolation of Swine Bone Marrow Lin-/CD45-/CD133 + Cells and Cardio-protective Effects of its Exosomes. Stem Cell Rev Rep 2023; 19:213-229. [PMID: 35925437 PMCID: PMC9822881 DOI: 10.1007/s12015-022-10432-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/19/2022] [Indexed: 01/29/2023]
Abstract
BACKGROUND The identification in murine bone marrow (BM) of CD133 + /Lin-/CD45- cells, possessing several features of pluripotent stem cells, encouraged us to investigate if similar population of cells could be also isolated from the swine BM. Heart failure is the terminal stage of many cardiovascular diseases, and its key pathological basis is cardiac fibrosis (CF). Research showed that stem cell derived exosomes may play a critical role in cardiac fibrosis. The effect of exosomes (Exos) on CF has remained unclear. OBJECTIVE To establish an isolation and amplification method of CD133 + /Lin-/CD45- cells from newbron swine BM in vitro, explore an highly efficient method to enrich swine bone marrow derived CD133 + /Lin-/CD45- cells and probe into their biological characteristics further. Furher more, to extract exosomes from it and explore its effect on CF. METHODS The mononuclear cells isolated from swine bone marrow by red blood cell (RBC) lysing buffer were coated by adding FcR blocking solution and coupled with CD133 antibody immunomagnetic beads, obtaining CD133 + cell group via Magnetic Activated Cell Sorting (MACS). In steps, the CD133 + /Lin-/CD45- cells were collected by fluorescence-activated cell sorting (FACS) labeled with CD133, Lin and CD45 antibodies, which were cultured and amplified in vitro. The biological features of CD133 + /Lin-/CD45- cells were studied in different aspects, including morphological trait observed with inverted microscope, ultrastructural characteristics observed under transmission electron microscope, expression of pluripotent markersidentified by immunofluorescent staining and Alkaline phosphatase staining. The Exos were extracted using a sequential centrifugation approach and its effects on CF were analyzed in Angiotensin II (Ang-II) induced-cardiac fibrosis in vivo. Rats in each group were treated for 4 weeks, and 2D echocardiography was adopted to evaluate the heart function. The degree of cardiac fibrosis was assessed by Hematoxylin-Eosin (HE) and Masson's trichrome staining. RESULTS The CD133 + /Lin-/CD45- cells accounted for about 0.2%-0.5% of the total mononuclear cells isolated from swine bone marrow. The combination of MACS and FACS to extract CD133 + /Lin-/CD45- cells could improved efficiency and reduced cell apoptosis. The CD133 + /Lin-/CD45- cells featured typical traits of pluripotent stem cells, the nucleus is large, mainly composed of euchromatin, with less cytoplasm and larger nucleoplasmic ratio, which expressed pluripotent markers (SSEA-1, Oct-4, Nanog and Sox-2) and alkaline phosphatase staining was positive.Animal experiment indicated that the cardiac injury related indexes (BNP、cTnI、CK-MB and TNF-α), the expression of key gene Smad3 and the degree of cardiac fibrosis in Exo treatment group were significantly reduced compared with the control group. 4 weeks after the treatment, cardiac ejection fraction (EF) value in the model group showed a remarkable decrease, indicating the induction of HF model. While Exo elevated the EF values, demonstrating cardio-protective effects. CONCLUSION The CD133 + /Lin-/CD45- cells derived from swine bone marrow were successfully isolated and amplified, laying a good foundation for further research on this promising therapeutic cell. The Exos may be a promising potential treatment strategy for CF.
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Affiliation(s)
- Hongxiao Li
- Medical College of Yangzhou University, Yangzhou, 225001, Jiangsu, China
- Department of Cardiology, Northern Jiangsu People's Hospital, Yangzhou, 225001, Jiangsu, China
| | - Jianjun Gu
- Medical College of Yangzhou University, Yangzhou, 225001, Jiangsu, China
- Department of Cardiology, Northern Jiangsu People's Hospital, Yangzhou, 225001, Jiangsu, China
| | - Xiaolin Sun
- Medical College of Yangzhou University, Yangzhou, 225001, Jiangsu, China
- Department of Cardiology, Northern Jiangsu People's Hospital, Yangzhou, 225001, Jiangsu, China
| | - Qisheng Zuo
- College of Animal Science and Technology, Yangzhou University, Yangzhou, 225001, Jiangsu, China
| | - Bichun Li
- College of Animal Science and Technology, Yangzhou University, Yangzhou, 225001, Jiangsu, China
| | - Xiang Gu
- Medical College of Yangzhou University, Yangzhou, 225001, Jiangsu, China.
- Department of Cardiology, Northern Jiangsu People's Hospital, Yangzhou, 225001, Jiangsu, China.
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Fonticoli L, Della Rocca Y, Rajan TS, Murmura G, Trubiani O, Oliva S, Pizzicannella J, Marconi GD, Diomede F. A Narrative Review: Gingival Stem Cells as a Limitless Reservoir for Regenerative Medicine. Int J Mol Sci 2022; 23:ijms23084135. [PMID: 35456951 PMCID: PMC9024914 DOI: 10.3390/ijms23084135] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 04/05/2022] [Accepted: 04/07/2022] [Indexed: 11/16/2022] Open
Abstract
The gingival tissue can be collected in an easy way and represent an accessible source to isolate gingival-derived mesenchymal stem cells (GMSCs). GMSCs are a subpopulation of dental-derived mesenchymal stem cells that show the mesenchymal stem cells (MSCs) features, such as differentiation abilities and immunomodulatory properties. Dental-derived stem cells are also expandable in vitro with genomic stability and the possibility to maintain the stemness properties over a prolonged period of passages. Moreover, several preclinical studies have documented that the extracellular vesicles (EVs) released from GMSCs possess similar biological functions and therapeutic effects. The EVs may represent a promising tool in the cell-free regenerative therapy approach. The present review paper summarized the GMSCs, their multi-lineage differentiation capacities, immunomodulatory features, and the potential use in the treatment of several diseases in order to stimulate tissue regeneration. GMSCs should be considered a good stem cell source for potential applications in tissue engineering and regenerative dentistry.
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Affiliation(s)
- Luigia Fonticoli
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | - Ylenia Della Rocca
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | | | - Giovanna Murmura
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | - Oriana Trubiani
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | - Stefano Oliva
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | | | - Guya Diletta Marconi
- Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
| | - Francesca Diomede
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
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Okić-Đorđević I, Obradović H, Kukolj T, Petrović A, Mojsilović S, Bugarski D, Jauković A. Dental mesenchymal stromal/stem cells in different microenvironments— implications in regenerative therapy. World J Stem Cells 2021; 13:1863-1880. [PMID: 35069987 PMCID: PMC8727232 DOI: 10.4252/wjsc.v13.i12.1863] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/15/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration. Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues, MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years. This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions, giving additional insight into the current clinical application of these cells.
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Affiliation(s)
- Ivana Okić-Đorđević
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Hristina Obradović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Tamara Kukolj
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Anđelija Petrović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Slavko Mojsilović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Diana Bugarski
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Aleksandra Jauković
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
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Stem Cells and Their Derivatives-Implications for Alveolar Bone Regeneration: A Comprehensive Review. Int J Mol Sci 2021; 22:ijms222111746. [PMID: 34769175 PMCID: PMC8583713 DOI: 10.3390/ijms222111746] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 10/25/2021] [Accepted: 10/27/2021] [Indexed: 02/07/2023] Open
Abstract
Oral and craniofacial bone defects caused by congenital disease or trauma are widespread. In the case of severe alveolar bone defect, autologous bone grafting has been considered a “gold standard”; however, the procedure has several disadvantages, including limited supply, resorption, donor site morbidity, deformity, infection, and bone graft rejection. In the last few decades, bone tissue engineering combined with stem cell-based therapy may represent a possible alternative to current bone augmentation techniques. The number of studies investigating different cell-based bone tissue engineering methods to reconstruct alveolar bone damage is rapidly rising. As an interdisciplinary field, bone tissue engineering combines the use of osteogenic cells (stem cells/progenitor cells), bioactive molecules, and biocompatible scaffolds, whereas stem cells play a pivotal role. Therefore, our work highlights the osteogenic potential of various dental tissue-derived stem cells and induced pluripotent stem cells (iPSCs), the progress in differentiation techniques of iPSCs into osteoprogenitor cells, and the efforts that have been made to fabricate the most suitable and biocompatible scaffold material with osteoinductive properties for successful bone graft generation. Moreover, we discuss the application of stem cell-derived exosomes as a compelling new form of “stem-cell free” therapy.
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