Immunomodulatory properties and in vivo osteogenesis of human dental stem cells from fresh and cryopreserved dental follicles

To date, three types of dental stem cells have been isolated: Dental Pulp Stem Cells (DPSC), Stem Cells From Human Exfoliated Deciduous Teeth (SHED) and Immature Dental Pulp Stem Cells (IDPC). These dental stem cells are considered as mesenchymal stem cells. They reside within the perivascular niche of dental pulp. They are highly proliferative, clonogenic, multipotent and are similar to mesenchymal Bone Marrow Stem Cells (BMSC). Also, they have high plasticity and can be easy isolated. The expressions of the alkaline phosphatase gene, dentin matrix protein 1 and dentinsialophosphoprotein are verified in these cells. Analyses of gene expression patterns indicated several genes which encode extracellular matrix components, cell adhesion molecules, growth factors and transcription regulators, cell signaling, cell communication or cell metabolism. In both conditions, in vivo and in vitro, these cells have the ability to differentiate into odontoblasts, chondrocytes, osteoblasts, adipocytes, neurons, melanocytes, smooth and skeletal muscles and endothelial cells. In vivo, after implantation, they have shown potential to differentiate into dentin but also into tissues like bone, adipose or neural tissue. In general, DPSCs are considered to have antiinflammatory and immunomodulatory abilities. After being grafted into allogenic tissues these cells are ableto induce immunological tolerance. Immunosuppressive effect is shown through the ability to inhibit proliferation of T lymphocytes. Dental pulp stem cells open new perspectives in therapeutic use not only in dentin regeneration, periodontal tissues and skeletoarticular, tissues of craniofacial region but also in treatment of neurotrauma, autoimmune diseases, myocardial infarction, muscular dystrophy and connective tissue damages.

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Immunomodulatory properties of adipose stem cells in vivo: Preclinical and clinical applications

10.1016/b978-0-12-819376-1.00019-6 ◽

2022 ◽

pp. 165-184

Author(s):

Matthias Waldner ◽

Fuat Baris Bengur ◽

Lauren Kokai

Keyword(s):

Stem Cells ◽

Clinical Applications ◽

Adipose Stem Cells ◽

Immunomodulatory Properties

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Eph/ephrin Signaling and Biology of Mesenchymal Stromal/Stem Cells

Journal of Clinical Medicine ◽

10.3390/jcm9020310 ◽

2020 ◽

Vol 9 (2) ◽

pp. 310 ◽

Cited By ~ 1

Author(s):

David Alfaro ◽

Mariano R. Rodríguez-Sosa ◽

Agustín G. Zapata

Keyword(s):

Stem Cells ◽

Therapeutic Agents ◽

Current Evidence ◽

Specific Cell ◽

Heterogeneous Cell Population ◽

Proliferation And Differentiation ◽

Ephrin Ligands ◽

Immunomodulatory Properties ◽

Stromal Stem Cells

Mesenchymal stromal/stem cells (MSCs) have emerged as important therapeutic agents, owing to their easy isolation and culture, and their remarkable immunomodulatory and anti-inflammatory properties. However, MSCs constitute a heterogeneous cell population which does not express specific cell markers and has important problems for in vivo homing, and factors regulating their survival, proliferation, and differentiation are largely unknown. Accordingly, in the present article, we review the current evidence on the relationships between Eph kinase receptors, their ephrin ligands, and MSCs. These molecules are involved in the adult homeostasis of numerous tissues, and we and other authors have demonstrated their expression in human and murine MSCs derived from both bone marrow and adipose tissue, as well as their involvement in the MSC biology. We extend these studies providing new results on the effects of Eph/ephrins in the differentiation and immunomodulatory properties of MSCs.

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Induction of Indoleamine 2,3-Dioxygenase Expression by Interferon-g in Human Mesenchymal Stem Cells Inhibits Graft Versus Host Disease

Blood ◽

10.1182/blood.v118.21.4698.4698 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4698-4698

Author(s):

Myoung Woo Lee ◽

Dae Seong Kim ◽

Hye Jin Kim ◽

Meong Hi Son ◽

Soo Hyun Lee ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Mesenchymal Stem Cells ◽

T Cell ◽

T Cell Proliferation ◽

Activated T Cells ◽

Graft Versus Host ◽

Ifn Γ ◽

Immunomodulatory Properties

Abstract Abstract 4698 Background: It is important to overcome the limitations such as graft rejection and graft versus host disease (GvHD) in allogeneic hematopoietic stem cell transplantation. Mesenchymal stem cells (MSCs), which evoke only minimal immune reactivity, may have anti-inflammatory and immunomodulatory effects. Purpose: In this study, we aimed to identify the immunomodulatory properties of human MSCs and to elucidate the possible mechanism of their properties for clinical treatment of allogeneic conflicts using MSCs. Materials & Methods: We conducted a comparative analysis about the immunomodulatory properties of MSCs derived from adult human tissues, including bone marrow (BM), adipose tissues (AT), umbilical cord blood (CB), and cord Wharton's jelly (WJ), in vitro and in vivo models. Results: AT-MSCs, CB-MSCs, and WJ-MSCs effectively suppressed phytohemagglutinin (PHA)-induced T-cell proliferation as effectively as did BM-MSCs. Levels of interferon (IFN)-g secreted from activated T-cells increased over time, but these levels were significantly reduced when cocultured with each type of MSCs. In addition, expression of indoleamine 2,3-dioxygenase (IDO) increased in MSCs treated with IFN-γ via JAK/STAT1 signaling pathways. Treatment with anti-IFN-g antibodies, JAK1/2 inhibitor or STAT1 siRNA restored PHA-induced T-cell proliferation. Use of an antagonist, 1-methyl-L-tryptophan, also restored PHA-induced T-cell proliferation, suggesting that IDO contributes to IFN-g-induced immunosuppression in MSCs. Moreover, infusion of IFN-g-treated MSCs decreased symptoms for human peripheral blood-derived mononuclear cells-induced GvHD in NOD/SCID mice, which resulted in an increase of survival rate of in vivo GvHD model. Conclusion: These data indicate that IFN-γ produced by activated T-cells is correlated with induction of IDO expression in MSCs by IFN-γ receptor/JAK/STAT1 pathway, which resulted in suppression of T-cell proliferation. Our findings suggest that MSCs derived from BM, AT, CB, or WJ could be used for clinical treatment of allogeneic conflicts. Disclosures: No relevant conflicts of interest to declare.

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Hypes and Hopes of Stem Cell Therapies in Dentistry: a Review

Stem Cell Reviews and Reports ◽

10.1007/s12015-021-10326-4 ◽

2022 ◽

Author(s):

Alessandra Rodriguez y Baena ◽

Andrea Casasco ◽

Manuela Monti

Keyword(s):

Stem Cells ◽

Temporal Dynamics ◽

3D Cell Culture ◽

Basic Research ◽

Science Research ◽

Dental Stem Cells ◽

Exciting Field ◽

Cell Therapies

AbstractOne of the most exciting advances in life science research is the development of 3D cell culture systems to obtain complex structures called organoids and spheroids. These 3D cultures closely mimic in vivo conditions, where cells can grow and interact with their surroundings. This allows us to better study the spatio-temporal dynamics of organogenesis and organ function. Furthermore, physiologically relevant organoids cultures can be used for basic research, medical research, and drug discovery. Although most of the research thus far focuses on the development of heart, liver, kidney, and brain organoids, to name a few, most recently, these structures were obtained using dental stem cells to study in vitro tooth regeneration. This review aims to present the most up-to-date research showing how dental stem cells can be grown on specific biomaterials to induce their differentiation in 3D. The possibility of combining engineering and biology principles to replicate and/or increase tissue function has been an emerging and exciting field in medicine. The use of this methodology in dentistry has already yielded many interesting results paving the way for the improvement of dental care and successful therapies. Graphical abstract

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Sinking Our Teeth in Getting Dental Stem Cells to Clinics for Bone Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms22126387 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6387

Author(s):

Sarah Hani Shoushrah ◽

Janis Lisa Transfeld ◽

Christian Horst Tonk ◽

Dominik Büchner ◽

Steffen Witzleben ◽

...

Keyword(s):

Stem Cells ◽

Tissue Regeneration ◽

Disease Modeling ◽

Pharmaceutical Research ◽

Cellular Systems ◽

Dental Stem Cells ◽

Hard Tissue ◽

Dental Tissues

Dental stem cells have been isolated from the medical waste of various dental tissues. They have been characterized by numerous markers, which are evaluated herein and differentiated into multiple cell types. They can also be used to generate cell lines and iPSCs for long-term in vitro research. Methods for utilizing these stem cells including cellular systems such as organoids or cell sheets, cell-free systems such as exosomes, and scaffold-based approaches with and without drug release concepts are reported in this review and presented with new pictures for clarification. These in vitro applications can be deployed in disease modeling and subsequent pharmaceutical research and also pave the way for tissue regeneration. The main focus herein is on the potential of dental stem cells for hard tissue regeneration, especially bone, by evaluating their potential for osteogenesis and angiogenesis, and the regulation of these two processes by growth factors and environmental stimulators. Current in vitro and in vivo publications show numerous benefits of using dental stem cells for research purposes and hard tissue regeneration. However, only a few clinical trials currently exist. The goal of this review is to pinpoint this imbalance and encourage scientists to pick up this research and proceed one step further to translation.

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Immunomodulatory properties and in vivo osteogenesis of mesenchymal stem cells from cryopreserved human dental follicle tissues

International Journal of Oral and Maxillofacial Surgery ◽

10.1016/j.ijom.2015.08.734 ◽

2015 ◽

Vol 44 ◽

pp. e122

Author(s):

B.W. Park ◽

H.J. Lee ◽

Y.H. Kang ◽

S.J. Jang ◽

G.J. Rho

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Dental Follicle ◽

Immunomodulatory Properties

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Osteogenic Potential of Dental Mesenchymal Stem Cells in Preclinical Studies: A Systematic Review Using Modified ARRIVE and CONSORT Guidelines

Stem Cells International ◽

10.1155/2015/378368 ◽

2015 ◽

Vol 2015 ◽

pp. 1-28 ◽

Cited By ~ 18

Author(s):

Murali Ramamoorthi ◽

Mohammed Bakkar ◽

Jack Jordan ◽

Simon D. Tran

Keyword(s):

Stem Cells ◽

Bone Regeneration ◽

Meta Analysis ◽

In Vitro Studies ◽

Osteogenic Potential ◽

Dental Stem Cells ◽

Promising Alternative ◽

Animal Trials

Background and Objective. Dental stem cell-based tissue engineered constructs are emerging as a promising alternative to autologous bone transfer for treating bone defects. The purpose of this review is to systematically assess the preclinical in vivo and in vitro studies which have evaluated the efficacy of dental stem cells on bone regeneration.Methods. A literature search was conducted in Ovid Medline, Embase, PubMed, and Web of Science up to October 2014. Implantation of dental stem cells in animal models for evaluating bone regeneration and/or in vitro studies demonstrating osteogenic potential of dental stem cells were included. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used to ensure the quality of the search. Modified ARRIVE (Animal research: reporting in invivo experiments) and CONSORT (Consolidated reporting of trials) were used to critically analyze the selected studies.Results. From 1914 citations, 207 full-text articles were screened and 137 studies were included in this review. Because of the heterogeneity observed in the studies selected, meta-analysis was not possible.Conclusion. Both in vivo and in vitro studies indicate the potential use of dental stem cells in bone regeneration. However well-designed randomized animal trials are needed before moving into clinical trials.

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