Stem Cells In Periodontal Regeneration Research Articles

Stem cell-based therapy in periodontal regeneration: a systematic review and meta-analysis of clinical studies

BackgroundPeriodontitis 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.MethodsThe 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.ResultsFive 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).ConclusionThe 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.

Impact of Oral Mesenchymal Stem Cells Applications as a Promising Therapeutic Target in the Therapy of Periodontal Disease

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.

Therapeutic potential of adipose tissue stem cells for periodontal regeneration.

Therapeutic potential of adipose tissue stem cells for periodontal regeneration.

Clinical application of mesenchymal stem cells in periodontal regeneration: A systematic review and meta-analysis.

To evaluate the potential efficacy of mesenchymal stem cells (MSCs) in periodontal regeneration in humans on the following main outcomes: clinical attachment level (CAL), probing depth (PD), and gingival recession (GR). The clinical application of stem cells in periodontal regeneration has begun in recent years, but clinical practices are not yet standardized and no recommendations are available at this time. Electronic database searches and hand searches were conducted. All types of studies, case series, and case reports were qualitatively described. Double-blind randomized controlled trials (RCTs) evaluating MSCs in periodontal regeneration were included in a meta-analysis if they compared administration of MSCs vs application of stem cell-free therapy in the control group, in healthy patients with periodontal defects, with a minimum of three mo of follow-up. Fifteen reports were included in qualitative analysis, involving 123 patients and 158 periodontal defects. Only two small RCTs at high risk of bias, with a total of 59 patients and 70 periodontal defects, were included in the meta-analysis. A small but significant difference between test and control groups was found for CAL at three mo (-0.90mm, 95% CI [-1.51; -0.29]), but not for PD and GR. Low-quality evidence suggests that MSC-based therapy may have a small impact on periodontal regeneration. However, due to the monocentric character, the small sample size, and potential heterogeneity across the two included RCTs, these results must not be considered as definitive. High-quality RCTs are needed before any clinical use of MSCs in periodontal regeneration.

Application of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets for Periodontal Regeneration.

Periodontitis is a chronic inflammatory disorder that causes destruction of the periodontal attachment apparatus including alveolar bone, the periodontal ligament, and cementum. Dental implants have been routinely installed after extraction of periodontitis-affected teeth; however, recent studies have indicated that many dental implants are affected by peri-implantitis, which progresses rapidly because of the failure of the immune system. Therefore, there is a renewed focus on periodontal regeneration aroundnatural teeth. To regenerate periodontal tissue, many researchers and clinicians have attempted to perform periodontal regenerative therapy using materials such as bioresorbable scaffolds, growth factors, and cells. The concept of guided tissue regeneration, by which endogenous periodontal ligament- and alveolar bone-derived cells are preferentially proliferated by barrier membranes, has proved effective, and various kinds of membranes are now commercially available. Clinical studies have shown the significance of barrier membranes for periodontal regeneration; however, the technique is indicated only for relatively small infrabony defects. Cytokine therapies have also been introduced to promote periodontal regeneration, but the indications are also for small size defects. To overcome this limitation, ex vivo expanded multipotent mesenchymal stromal cells (MSCs) have been studied. In particular, periodontal ligament-derived multipotent mesenchymal stromal cells are thought to be a responsible cell source, based on both translational and clinical studies. In this review, responsible cell sources for periodontal regeneration and their clinical applications are summarized. In addition, recent transplantation strategies and perspectives about the cytotherapeutic use of stem cells for periodontal regeneration are discussed.

Concise Review: Periodontal Tissue Regeneration Using Stem Cells: Strategies and Translational Considerations.

Periodontitis is a widespread disease characterized by inflammation‐induced progressive damage to the tooth‐supporting structures until tooth loss occurs. The regeneration of lost/damaged support tissue in the periodontium, including the alveolar bone, periodontal ligament, and cementum, is an ambitious purpose of periodontal regenerative therapy and might effectively reduce periodontitis‐caused tooth loss. The use of stem cells for periodontal regeneration is a hot field in translational research and an emerging potential treatment for periodontitis. This concise review summarizes the regenerative approaches using either culture‐expanded or host‐mobilized stem cells that are currently being investigated in the laboratory and with preclinical models for periodontal tissue regeneration and highlights the most recent evidence supporting their translational potential toward a widespread use in the clinic for combating highly prevalent periodontal disease. We conclude that in addition to in vitro cell‐biomaterial design and transplantation, the engineering of biomaterial devices to encourage the innate regenerative capabilities of the periodontium warrants further investigation. In comparison to cell‐based therapies, the use of biomaterials is comparatively simple and sufficiently reliable to support high levels of endogenous tissue regeneration. Thus, endogenous regenerative technology is a more economical and effective as well as safer method for the treatment of clinical patients. stem cells translational medicine 2019;8:392–403

Combination of Bioactive Polymeric Membranes and Stem Cells for Periodontal Regeneration: In Vitro and In Vivo Analyses.

Regeneration of periodontal tissues requires a concerted effort to obtain consistent and predictable results in vivo. The aim of the present study was to test a new family of bioactive polymeric membranes in combination with stem cell therapy for periodontal regeneration. In particular, the novel polyester poly(isosorbide succinate-co-L-lactide) (PisPLLA) was compared with poly(L-lactide) (PLLA). Both polymers were combined with collagen (COL), hydroxyapatite (HA) and the growth factor bone morphogenetic protein-7 (BMP7), and their osteoinductive capacity was evaluated via in vitro and in vivo experiments. Membranes composed of PLLA/COL/HA or PisPLLA/COL/HA were able to promote periodontal regeneration and new bone formation in fenestration defects in rat jaws. According to quantitative real-time polymerase chain reaction (qRT-PCR) and Alizarin Red assays, better osteoconductive capacity and increased extracellular mineralization were observed for PLLA/COL/HA, whereas better osteoinductive properties were associated with PisPLLA/COL/HA. We concluded that membranes composed of either PisPLLA/COL/HA or PLLA/COL/HA present promising results in vitro as well as in vivo and that these materials could be potentially applied in periodontal regeneration.

Is There a Role for Neural Crest Stem Cells in Periodontal Regeneration?

The ultimate goal of periodontal treatment is not only the stabilization of periodontal disease but also regeneration of the periodontal tissues destroyed by severe periodontitis. The tissue engineering triad of stem cells, biological signals, and cell-seeded scaffold provides a biological template for tissue regeneration. Neural crest stem cells (NCSC) comprise a transient multipotent stem cell population that initially emerges from the junction of the epidermal and neural ectoderm through reciprocal interactions between these tissues and signals from the mesoderm during embryonic development of vertebrates. The cells then migrate to their destination in the embryo and differentiate into various dental mesenchymal stem cells which give rise to most components of the dental tissues, including periodontal ligament (PDL), alveolar bone, cementum, dental pulp, and dentin. The crucial role that NCSC play in embryonic development makes them a highly promising stem cell population for use in the regeneration of periodontal tissues. Here, we review the current understanding of the features and functions of NCSC-derived cells in dental tissues. We additionally discuss the possibility that NCSC contribute to the regeneration of periodontal tissues.

The Scope of Stem Cells in Periodontal Regeneration

Yamada N, Okano T, Sakai H, Karikusa F, Sawasaki Y, Sakurai Y. Thermo-responsive polymeric surfaces; control of attachment and detachment of cultured cells. Makromol Chem Rapid Commun. 1990; 11(11):571-576.

The Scope of Stem Cells in Periodontal Regeneration

Yamada N, Okano T, Sakai H, Karikusa F, Sawasaki Y, Sakurai Y. Thermo-responsive polymeric surfaces; control of attachment and detachment of cultured cells. Makromol Chem Rapid Commun. 1990; 11(11):571-576.

Periodontal ligament-derived cells for periodontal regeneration in animal models: a systematic review.

Implantation of periodontal ligament stem cells is emerging as a potential periodontal regenerative procedure. This systematic review considers the evidence from animal models investigating the use of periodontal ligament stem cells for successful periodontal regeneration. PubMed, Embase, MEDLINE and Google Scholar were searched to December 2013 for quantitative studies examining the outcome of implanting periodontal ligament stem cells into experimental periodontal defects in animals. Inclusion criteria were: implantation of periodontal ligament stem cells into surgically created periodontal defects for periodontal regeneration; animal models only; source of cells either human or animal; and published in English. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. From the literature search, 43 studies met the inclusion criteria. A wide variety of surgical defects were created in four species of animal (dog, rat, pig and sheep). Owing to wide variability in defect type, cell source and cell scaffold, no meta-analysis was possible. Outcome measures included new bone, new cementum and new connective tissue formation. In 70.5% of the results, statistically significant improvements of these measures was recorded. These results are notable in that they indicate that irrespective of the defect type and animal model used, periodontal ligament stem cell implantation can be expected to result in a beneficial outcome for periodontal regeneration. It is recommended that there is sufficient evidence from preclinical animal studies to warrant moving to human studies to examine the efficacy, safety, feasibility (autologous vs. allogeneic transplantation) and delivery of periodontal ligament stem cells for periodontal regeneration.

Stem cells, tissue engineering and periodontal regeneration

The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal-regenerative potential of stem cells. We consider and describe the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow-derived mesenchymal stem cells and the main dental-derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.

Stem Cells in Periodontal Regeneration

Regeneration medicine, in particular that using stem cells, has received considerable amount of attention in recent years and also in field of Periodontology, in which bone regeneration is biologically possible but many times clinically unpredictable. The science of stem cells therapy has potential to lead to treatments for major degenerative diseases, by providing healthy cells to replace diseased tissues and organs. Stem cell therapy can also be used to deliver healthy genes to organs with missing or defective proteins. This book is complete and detailed presentation of stem cells therapies and its role in periodontal regeneration. This book also describes the sources of stem cells and future perspectives. The promise of stem cells therapies is an exciting one, but still it’s under research and book also entails details regarding the studies done on role of stem cells in periodontal regeneration.

Somatic Stem Cell Biology and Periodontal Regeneration

Somatic stem cells have been acknowledged for their ability to differentiate into multiple cell types and their capacity for self-renewal. Some mesenchymal stem cells play a dominant role in the repair and reconstruction of periodontal tissues. Both dental-derived and some non-dental-derived mesenchymal stem cells possess the capacity for periodontal regeneration under certain conditions with induced differentiation, proliferation, cellular secretion, and their interactions. Stem cell-based tissue engineering technology promises to bring improvements to periodontal regeneration, biologic tooth repair, and bioengineered implants. The present review discusses the roles and values of various somatic stem cells in periodontal regeneration.

Clinical utility of stem cells for periodontal regeneration

The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal-regenerative potential of stem cells. We considered and described the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow-derived mesenchymal stem cells and the main dental-derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.