Human Dental Pulp Stem Cells Suppress Alloantigen-induced Immunity by Stimulating T Cells to Release Transforming Growth Factor Beta

Kwack, Kyu Hwan; Lee, Jung Min; Park, Sang Hyuk; Lee, Hyeon Woo

doi:10.1016/j.joen.2016.09.005

Cited by 41 publications

(44 citation statements)

References 32 publications

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“…IFN-γ secreted by activated PBMCs induce the expression of soluble factors by DPSCs, which may play an important role in the immunosuppressive process [ 50 ]. Expression of PGE2, TGF-β, indolamine-2, 3-dioxygenase-1 (IDO1), IL-6, IL-10, and COX2 triggers the immunosuppressive activity of DPSCs [ 51 – 55 ]. The present study demonstrated that genes related to immunomodulation including prostaglandin E synthase ( PTGES ), COX-2 , IL-6 , TGF-β , and IDO1 were similarly expressed in canine MDPSCs compared to canine mobilized adipose-derived MSCs.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic transplantation of mobilized dental pulp stem cells with the mismatched dog leukocyte antigen type is safe and efficacious for total pulp regeneration

et al. 2018

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BackgroundWe recently demonstrated that autologous transplantation of mobilized dental pulp stem cells (MDPSCs) was a safe and efficacious potential therapy for total pulp regeneration in a clinical study. The autologous MDPSCs, however, have some limitations to overcome, such as limited availability of discarded teeth from older patients. In the present study, we investigated whether MDPSCs can be used for allogeneic applications to expand their therapeutic use.MethodsAnalysis of dog leukocyte antigen (DLA) was performed using polymerase chain reaction from blood. Canine allogeneic MDPSCs with the matched and mismatched DLA were transplanted with granulocyte-colony stimulating factor in collagen into pulpectomized teeth respectively (n = 7, each). Results were evaluated by hematoxylin and eosin staining, Masson trichrome staining, PGP9.5 immunostaining, and BS-1 lectin immunostaining performed 12 weeks after transplantation. The MDPSCs of the same DLA used in the first transplantation were further transplanted into another pulpectomized tooth and evaluated 12 weeks after transplantation.ResultsThere was no evidence of toxicity or adverse events of the allogeneic transplantation of the MDPSCs with the mismatched DLA. No adverse event of dual transplantation of the MDPSCs with the matched and mismatched DLA was observed. Regenerated pulp tissues including neovascularization and neuronal extension were quantitatively and qualitatively similar at 12 weeks in both matched and mismatched DLA transplants. Regenerated pulp tissue was similarly observed in the dual transplantation as in the single transplantation of MDPSCs both with the matched and mismatched DLA.ConclusionsDual allogeneic transplantation of MDPSCs with the mismatched DLA is a safe and efficacious method for total pulp regeneration.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0855-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Allogeneic transplantation of mobilized dental pulp stem cells with the mismatched dog leukocyte antigen type is safe and efficacious for total pulp regeneration

et al. 2018

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“…An upregulated expression of TLR4 appeared to increase the expression of IL-8 in DPSCs [ 114 ], particularly in SCI crush injury where IL-8 preserves axon integrity and decreases cavitation [ 115 , 116 ]. DPSCs also express TGF- β , HGF, and indoleamine 2,3-dioxygenase (IDO) without prior activation [ 117 , 118 ] and suppress the proliferation of peripheral blood mononuclear cells and the activation of T cells [ 119 , 120 ]. Coculture of DPSCs and T cells promoted T cell secretion of human leukocyte antigen-G, vascular adhesion molecule-1, intracellular adhesion molecule-1, IL-6, TGF- β , HGF, and IL-10, while it downregulated proinflammatory cytokines such as IL-2, IL-6 receptor, IL-12, IL-17A, and tumor necrosis factor- α (TNF- α ) [ 121 ].…”

Section: Dental Pulp Stem Cells (Dpscs)mentioning

confidence: 99%

“…The results of the intraperitoneal injection of DPSCs into Balb/c(H-2 d ) mice demonstrated that DPSCs had a meaningful effect on mixed lymphocyte reaction [ 125 ]. Studies of Kwack et al demonstrated that DPSCs could inhibit acute allogeneic immune responses by the release of TGF- β as a result of allogeneic stimulation of T lymphocytes and provide a novel insight for the allogeneic transplantation of DPSCs in future clinical use [ 120 ]. Recent animal studies conclude that DPSCs could modulate immune tolerance and influence apoptosis via T cells and lymphocytes.…”

Section: Dental Pulp Stem Cells (Dpscs)mentioning

confidence: 99%

Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair

Luo

Wang

et al. 2018

Stem Cells International

114

144

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This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases.

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“…Earlier reports have proven that the addition of DPSCs can inhibit the T-cell response up to 91% while BMSCs allowed only 75% inhibition of T-cell response, highlighting the possible use of DPSCs in different individuals or to be used for immune therapy (Pierdomenico et al, 2005 ; Ding et al, 2015 ). The dental pulp of healthy young patients appears to possess the generic MSC phenotype and can strongly inhibit acute allogeneic immune responses resulting from T-lymphocyte stimulation again through their release of TGF-β (Kwack et al, 2017 ). This provides insight into the potential clinical use of hDPSCs for dental and non-dental tissue regeneration using allogeneic transplantation, that will move the field of stem cell therapy into true clinical application faster than before.…”

Section: Translational Regenerative Dentistry For the Futurementioning

confidence: 99%

Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement

Marei

Backly

2018

Front. Bioeng. Biotechnol.

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Dentistry is a continuously changing field that has witnessed much advancement in the past century. Prosthodontics is that branch of dentistry that deals with replacing missing teeth using either fixed or removable appliances in an attempt to simulate natural tooth function. Although such “replacement therapies” appear to be easy and economic they fall short of ever coming close to their natural counterparts. Complications that arise often lead to failures and frequent repairs of such devices which seldom allow true physiological function of dental and oral-maxillofacial tissues. Such factors can critically affect the quality of life of an individual. The market for dental implants is continuously growing with huge economic revenues. Unfortunately, such treatments are again associated with frequent problems such as peri-implantitis resulting in an eventual loss or replacement of implants. This is particularly influential for patients having co-morbid diseases such as diabetes or osteoporosis and in association with smoking and other conditions that undoubtedly affect the final treatment outcome. The advent of tissue engineering and regenerative medicine therapies along with the enormous strides taken in their associated interdisciplinary fields such as stem cell therapy, biomaterial development, and others may open arenas to enhancing tissue regeneration via designing and construction of patient-specific biological and/or biomimetic substitutes. This review will overview current strategies in regenerative dentistry while overviewing key roles of dental mesenchymal stem cells particularly those of the dental pulp, until paving the way to precision/translational regenerative medicine therapies for future clinical use.

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Human Dental Pulp Stem Cells Suppress Alloantigen-induced Immunity by Stimulating T Cells to Release Transforming Growth Factor Beta

Cited by 41 publications

References 32 publications

Allogeneic transplantation of mobilized dental pulp stem cells with the mismatched dog leukocyte antigen type is safe and efficacious for total pulp regeneration

Allogeneic transplantation of mobilized dental pulp stem cells with the mismatched dog leukocyte antigen type is safe and efficacious for total pulp regeneration

Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair

Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement

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