Modulating Therapeutic Properties of Oral Tissue-Derived Mesenchymal Stem Cells

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 30573

Special Issue Editor

Special Issue Information

Dear Colleagues,

Mesenchymal stem cells have been shown to exhibit significant regenerative potential and have also shown immunomodulatory properties, allowing them to be introduced into a host without eliciting any adverse immune response. Additionally, mesenchymal stem cells have been shown to exhibit tropism toward injured/pathological sites, thus allowing for a targeted therapeutic modality.

Oral-tissue-derived mesenchymal stem cells have gained popularity due to their ready availability, especially mesenchymal stem cells derived from the exfoliated human primary tooth and the human permanent tooth extracted for orthodontic purposes. Despite the increasing number of applications of oral-tissue-derived mesenchymal stem cells, their regenerative potential has been shown to exhibit limitations. Thus, there is an increasing interest in the modulation of the various properties of oral tissue-derived mesenchymal stem cells to enhance their regenerative ability. The present Special Issue will focus on the augmentation of the regenerative potential of oral-tissue-derived mesenchymal stem cells through pre-conditioning with various pharmaceutical agents. Articles assessing the modulation of key mesenchymal stem cell properties, including the potential for differentiation, tropism, mineralization, angiogenesis, clonogenicity, senescence resistance, immunomodulation, recovery following short and long-term preservation, etc. will be considered for publication.

We invite authors to submit original research articles and clinical studies. Review articles are also welcome if they summarize the synthesis of new approaches in these fields.

Prof. Dr. Luca Testarelli
Guest Editor

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Keywords

  • Dental pulp stem cells
  • Gingival stem cells
  • SHEDs
  • Tissue regeneration
  • Mesenchymal stem cell
  • Oral tissue regeneration

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Published Papers (6 papers)

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Research

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10 pages, 2566 KiB  
Article
Effect of Different Intracanal Medicaments on the Viability and Survival of Dental Pulp Stem Cells
by Shilpa Bhandi, Shankargouda Patil, Nezar Boreak, Hitesh Chohan, Abdulaziz S. AbuMelha, Mazen F. Alkahtany, Khalid H. Almadi, Thilla Sekar Vinothkumar, A. Thirumal Raj and Luca Testarelli
J. Pers. Med. 2022, 12(4), 575; https://doi.org/10.3390/jpm12040575 - 4 Apr 2022
Cited by 11 | Viewed by 2977
Abstract
Background: Stem cells play an important role in the success of regenerative endodontic procedures. They are affected by the presence of medicaments that are used before the induction of bleeding or the creation of a scaffold for endodontic regeneration. This study examines the [...] Read more.
Background: Stem cells play an important role in the success of regenerative endodontic procedures. They are affected by the presence of medicaments that are used before the induction of bleeding or the creation of a scaffold for endodontic regeneration. This study examines the effects of different intracanal medicaments on the viability and survival of dental pulp stem cells at different doses and over different exposure times. Methods: Dental pulp stem cells were cultured from healthy third molar teeth using the long-term explant culture method and characterized using flow cytometry and exposed to different concentrations of calcium hydroxide, doxycycline, potassium iodide, triamcinolone, and glutaraldehyde, each ranging from 0 (control) to 1000 µg/mL. Exposure times were 6, 24, and 48 h. Cell viability was measured using the MTT assay, and apoptosis was measured using the Annexin V-binding assay. Results: All medicaments significantly reduced cell viability at different concentrations over different exposure times. Calcium hydroxide and triamcinolone favored cell viability at higher concentrations during all exposure times compared to other medicaments. The apoptosis assay showed a significant increase in cell death on exposure to doxycycline, potassium iodide, and glutaraldehyde. Conclusion: The intracanal medicaments examined in our study affected the viability of dental pulp stem cells in a time and dose-dependent manner. They also adversely affected the survival of dental pulp stem cells. Further studies are needed to better understand the effect of prolonged exposure to medicaments according to clinical protocols and their effect on the stemness of dental pulp stem cells. Full article
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11 pages, 3063 KiB  
Article
Efficacy of Laser Doppler Flowmetry, as a Diagnostic Tool in Assessing Pulp Vitality of Traumatised Teeth: A Split Mouth Clinical Study
by Ani Belcheva, Maria Shindova and Reem Hanna
J. Pers. Med. 2021, 11(8), 801; https://doi.org/10.3390/jpm11080801 - 17 Aug 2021
Cited by 4 | Viewed by 3762
Abstract
Aim: This study aimed to evaluate the efficacy of laser Doppler flowmetry (LDF) in determining the changes in the pulpal blood flow (PBF) during post-traumatic period of the traumatised permanent teeth. Methods: 88 teeth of 44 patients (mean age 10.30 ± 2.38) were [...] Read more.
Aim: This study aimed to evaluate the efficacy of laser Doppler flowmetry (LDF) in determining the changes in the pulpal blood flow (PBF) during post-traumatic period of the traumatised permanent teeth. Methods: 88 teeth of 44 patients (mean age 10.30 ± 2.38) were recruited according to the eligibility criteria and divided into two groups: test group (44 traumatised teeth) and control group (44 sound and healthy teeth). The measurement of PBF was performed, using a LDF monitor. Results: The analysis of the LDF outcomes in function of diagnosis indicated that the measurements of the traumatised teeth were significantly higher than those of non-traumatised teeth (p ˂ 0.05). Conclusions: LDF application provides dentists with fundamental benefits in terms of an early and precise investigation of PBF. In addition, LDF is a useful monitoring tool for revascularization of traumatised teeth and reliable objective diagnostic indicator of pulp vitality. Trial registration: ClinicalTrials.gov (Registration number: NCT04967456). Full article
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18 pages, 3718 KiB  
Article
Similar Features, Different Behaviors: A Comparative In Vitro Study of the Adipogenic Potential of Stem Cells from Human Follicle, Dental Pulp, and Periodontal Ligament
by Melissa D. Mercado-Rubio, Erick Pérez-Argueta, Alejandro Zepeda-Pedreguera, Fernando J. Aguilar-Ayala, Ricardo Peñaloza-Cuevas, Angela Kú-González, Rafael A. Rojas-Herrera, Beatriz A. Rodas-Junco and Geovanny I. Nic-Can
J. Pers. Med. 2021, 11(8), 738; https://doi.org/10.3390/jpm11080738 - 28 Jul 2021
Cited by 10 | Viewed by 4097
Abstract
Dental tissue-derived mesenchymal stem cells (DT-MSCs) are a promising resource for tissue regeneration due to their multilineage potential. Despite accumulating data regarding the biology and differentiation potential of DT-MSCs, few studies have investigated their adipogenic capacity. In this study, we have investigated the [...] Read more.
Dental tissue-derived mesenchymal stem cells (DT-MSCs) are a promising resource for tissue regeneration due to their multilineage potential. Despite accumulating data regarding the biology and differentiation potential of DT-MSCs, few studies have investigated their adipogenic capacity. In this study, we have investigated the mesenchymal features of dental pulp stem cells (DPSCs), as well as the in vitro effects of different adipogenic media on these cells, and compared them to those of periodontal ligament stem cells (PLSCs) and dental follicle stem cells (DFSCs). DFSC, PLSCs, and DPSCs exhibit similar morphology and proliferation capacity, but they differ in their self-renewal ability and expression of stemness markers (e.g OCT4 and c-MYC). Interestingly, DFSCs and PLSCs exhibited more lipid accumulation than DPSCs when induced to adipogenic differentiation. In addition, the mRNA levels of adipogenic markers (PPAR, LPL, and ADIPOQ) were significantly higher in DFSCs and PLSCs than in DPSCs, which could be related to the differences in the adipogenic commitment in those cells. These findings reveal that the adipogenic capacity differ among DT-MSCs, features that might be advantageous to increasing our understanding about the developmental origins and regulation of adipogenic commitment. Full article
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12 pages, 31731 KiB  
Article
LINC00084/miR-204/ZEB1 Axis Mediates Myofibroblastic Differentiation Activity in Fibrotic Buccal Mucosa Fibroblasts: Therapeutic Target for Oral Submucous Fibrosis
by Yu-Hsien Lee, Yi-Wen Liao, Ming-Yi Lu, Pei-Ling Hsieh and Cheng-Chia Yu
J. Pers. Med. 2021, 11(8), 707; https://doi.org/10.3390/jpm11080707 - 23 Jul 2021
Cited by 16 | Viewed by 2477
Abstract
Oral submucosal fibrosis (OSF) is a precancerous condition in the oral cavity and areca nut consumption has been regarded as one of the etiologic factors implicated in the development of OSF via persistent activation of buccal mucosal fibroblasts (BMFs). It has been previously [...] Read more.
Oral submucosal fibrosis (OSF) is a precancerous condition in the oral cavity and areca nut consumption has been regarded as one of the etiologic factors implicated in the development of OSF via persistent activation of buccal mucosal fibroblasts (BMFs). It has been previously reported that an epithelial to mesenchymal transition (EMT) factor, ZEB1, mediated the areca nut-associated myofibroblast transdifferentiation. In the current study, we aimed to elucidate how areca nut affected non-coding RNAs and the subsequent myofibroblast activation via ZEB1. We found that long non-coding RNA LINC00084 was elicited in the BMFs treated with arecoline, a major alkaloid of areca nut, and silencing LINC00084 prevented the arecoline-induced activities (such as collagen gel contraction, migration, and wound healing capacities). The upregulation of LINC00084 was also observed in the OSF tissues and fibrotic BMFs (fBMFs), and positively correlated with several fibrosis factors. Moreover, we showed knockdown of LINC00084 markedly suppressed the myofibroblast features in fBMFs, including myofibroblast phenotypes and marker expression. The results from the luciferase reporter assay confirmed that LINC00084 acted as a sponge of miR-204 and miR-204 inhibited ZEB1 by directly interacting with it. Altogether, these findings suggested that the constant irritation of arecoline may result in upregulation of LINC00084 in BMFs, which increased the ZEB1 expression by sequestering miR-204 to induce myofibroblast transdifferentiation. Full article
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16 pages, 3891 KiB  
Article
3D Clumps/Extracellular Matrix Complexes of Periodontal Ligament Stem Cells Ameliorate the Attenuating Effects of LPS on Proliferation and Osteogenic Potential
by Spoorthi Ravi Banavar, Swati Yeshwant Rawal, Shaju Jacob Pulikkotil, Umer Daood, Ian C. Paterson, Fabian Amalraj Davamani, Mikihito Kajiya, Hidemi Kurihara, Suan Phaik Khoo and Eng Lai Tan
J. Pers. Med. 2021, 11(6), 528; https://doi.org/10.3390/jpm11060528 - 9 Jun 2021
Cited by 3 | Viewed by 3961
Abstract
Background: The effects of lipopolysaccharide (LPS) on cell proliferation and osteogenic potential (OP) of MSCs have been frequently studied. Objective: to compare the effects of LPS on periodontal-ligament-derived mesenchymal stem cells (PDLSCs) in monolayer and 3D culture. Methods: The PDLSCs were colorimetrically assessed [...] Read more.
Background: The effects of lipopolysaccharide (LPS) on cell proliferation and osteogenic potential (OP) of MSCs have been frequently studied. Objective: to compare the effects of LPS on periodontal-ligament-derived mesenchymal stem cells (PDLSCs) in monolayer and 3D culture. Methods: The PDLSCs were colorimetrically assessed for proliferation and osteogenic potential (OP) after LPS treatment. The 3D cells were manually prepared by scratching and allowing them to clump up. The clumps (C-MSCs) were treated with LPS and assessed for Adenosine triphosphate (ATP) and OP. Raman spectroscopy was used to analyze calcium salts, DNA, and proline/hydroxyproline. Multiplexed ELISA was performed to assess LPS induced local inflammation. Results: The proliferation of PDLSCs decreased with LPS. On Day 28, LPS-treated cells showed a reduction in their OP. C-MSCs with LPS did not show a decrease in ATP production. Principal bands identified in Raman analysis were the P–O bond at 960 cm−1 of the mineral component, 785 cm−1, and 855 cm−1 showing qualitative changes in OP, proliferation, and proline/hydroxyproline content, respectively. ELISA confirmed increased levels of IL-6 and IL-8 but with the absence of TNF-α and IL-1β secretion. Conclusions: These observations demonstrate that C-MSCs are more resistant to the effects of LPS than cells in monolayer cell culture. Though LPS stimulation of C-MSCs creates an early pro-inflammatory milieu by secreting IL-6 and IL-8, PDLSCs possess inactivated TNF promoter and an ineffective caspase-1 activating process. Full article
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Review

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20 pages, 2088 KiB  
Review
Vertical Root Fracture in Non-Endodontically and Endodontically Treated Teeth: Current Understanding and Future Challenge
by Wan-Chuen Liao, Chi-Hung Chen, Yu-Hwa Pan, Mei-Chi Chang and Jiiang-Huei Jeng
J. Pers. Med. 2021, 11(12), 1375; https://doi.org/10.3390/jpm11121375 - 16 Dec 2021
Cited by 28 | Viewed by 11493
Abstract
A vertical root fracture (VRF) is a complex complication that usually leads to tooth extraction. The aim of this article is to review the prevalence, demography, distribution, diagnostic methods, etiology and predisposing factors, clinical features, radiographic characteristics and treatment strategies of VRFs in [...] Read more.
A vertical root fracture (VRF) is a complex complication that usually leads to tooth extraction. The aim of this article is to review the prevalence, demography, distribution, diagnostic methods, etiology and predisposing factors, clinical features, radiographic characteristics and treatment strategies of VRFs in non-endodontically treated teeth (VRFNETT) and endodontically treated teeth (VRFETT). Search terms for each subject related to VRFNETT and VRFETT were entered into MEDLINE, PubMed and Google Scholar. Systematic reviews, retrospective cohort studies, demographic research, clinical studies, case reports and case series were reviewed. Most of the VRFs were found in patients older than 40 years old. Older populations were discovered in the non-endodontically treated VRF group when compared to the endodontically treated VRF group. Male patients were found at a greater prevalence than females in the non-endodontically treated VRF group. The initial occurrence of a VRF may accompany radiolucent lines within the root canal, unusual space between the canal wall and intracanal material, a widening of the PDL space along the periradicular surfaces, angular bony destruction, step-like bone defects, V-shaped diffuse bone defects, or root resorptions corresponding to the fracture line before the clear separation of the fractured fragment. The indicative clinical and radiographic signs of VRF included a coronally positioned sinus tract, deep-narrow periodontal defects, the displacement of a fractured fragment, periradicular radiolucent halos and the widening of the root canal space. Interestingly, VRFNETT are more often observed in the Chinese population. Some patients with multiple VRFs were observed, suggesting possible predisposing factors in genetics and tooth development. The management of a VRF usually involves a multidisciplinary approach. The common distribution and features of VRFNETT and VRFETT were elucidated to facilitate recognition and diagnosis. Besides extraction, variable therapeutic schemes, such as the repair of the VRF, root amputation and others reported in earlier literature, are available. A long-term prognosis study of the various therapeutic strategies is needed. Full article
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