Preventive effects of tonsil‐derived mesenchymal stem cells on osteoradionecrosis in a rat model

Park, Hae Sang; Lee, Jihae; Kim, Jin Woo; Kim, Ha Young; Jung, Soo Yeon; Lee, Sung Min; Park, Chan Hum; Kim, Hansu

doi:10.1002/hed.25004

Cited by 20 publications

(11 citation statements)

References 21 publications

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“…Recently, palatine tonsil tissue was also identified as a source of MSCs and tonsil-derived MSCs (T-MSCs) showed abundant expression of immunomodulatory proteins, compared with MSCs derived from the bone marrow and adipose tissue [15,16]. Moreover, studies for T-MSCs described an immunomodulatory effect on degenerative or inflammatory diseases [17][18][19][20]. Our previous study also demonstrated an immunomodulatory effect of T-MSCs in a mouse model of allergic rhinitis [21].…”

Section: Introductionmentioning

confidence: 95%

The Supernatant of Tonsil-Derived Mesenchymal Stem Cell Has Antiallergic Effects in Allergic Rhinitis Mouse Model

Park

Kim

Bae

et al. 2020

Mediators of Inflammation

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Background and Purpose. Recently, tonsil-derived mesenchymal stem cells (T-MSCs) have attracted great attention in various medical fields due to easier harvest of T-MSCs and more immunomodulatory effects than adipose-derived MSCs. However, there was still little evidence of the effect of conditioned media from T-MSCs (T-MSCs-CM) on allergic rhinitis (AR). Therefore, we investigated the impact of T-MSCs-CM on an AR mouse model. Methods. We isolated T-MSCs from human palatine tonsil and evaluated the ingredients of T-MSCs-CM. The effect of T-MSCs-CM was evaluated in the AR mouse model that was randomly divided into five groups (negative control, positive control, and T-MSCs-CM treated (0.1 mg, 1 mg, and 10 mg)). To investigate the therapeutic effect, we analyzed rhinitis symptoms, serum immunoglobulin (Ig), inflammatory cells, and cytokine expression. We also assessed T cell receptor signal, including MAP kinase (ERK/JNK), p65, and NFAT1. Results. We identified the increment of TGF-β1, PGE2, and HGF in the T-MSCs-CM. In an animal study, the T-MSCs-CM-treated group showed significantly reduced allergic symptoms and infiltration of eosinophils and neutrophils in the nasal mucosa, whereas there was no significant difference in total IgE and the OVA-specific IgE level. Additionally, we found that the 10 mg T-MSCs-CM-treated group showed a significantly decreased IL-4 mRNA expression, compared to the (+) Con group. In the analysis of T cell receptor signal, the phosphorylation of MAP kinases, translocation of p65, and activation of NFAT1 were inhibited after T-MSCs-CM. Conclusions. Our findings suggest that T-MSCs-CM showed a partial immunomodulatory effect on the AR mouse model by the inhibition of T cell activation via MAP kinase, p65, and NFAT1.

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Section: Introductionmentioning

confidence: 95%

The Supernatant of Tonsil-Derived Mesenchymal Stem Cell Has Antiallergic Effects in Allergic Rhinitis Mouse Model

Park

Kim

Bae

et al. 2020

Mediators of Inflammation

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“…It has been reported that the mortality rate is as high as 43% . According to an improved rat model, the mortality rate is 18.2%, due to anaesthetization for IR and asphyxia of teeth extraction. In the present study, we successfully created an ORN model in rats with improved survival rates up to 89% (16/18) by following modified modeling methods.…”

Section: Discussionmentioning

confidence: 99%

Protective role of α2‐macroglobulin against jaw osteoradionecrosis in a preclinical rat model

Kong

Chen

et al. 2018

J Oral Pathology Medicine

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Objective We have previously demonstrated the effect of alpha‐2‐macroglobulin (α2M) in the remediation of radiation‐induced cellular damage. Here, we investigated the protective effects of α2M in a preclinical rat model of jaw osteoradionecrosis (ORN). Methods Eighteen rats were divided randomly into three groups: the control group, the radiation therapy (RT) alone group, and the radiated mandibles pretreated with α2M (α2M + RT) group. One month after radiation, all left molar teeth were extracted. After another 3 months, the animals were sacrificed and body weight, histopathology, microcomputed tomography and immunofluorescence were evaluated in all groups. Results The RT group showed serious alopecia, bone exposure, inflammation, necrosis, fibrosis, and the absence of new bone formation within the socket. The α2M + RT group exhibited less alopecia than the RT group and slight inflammation and fibrosis in the bone marrow cavity. The cortical bone was similar to normal bone tissue. Interestingly, compared with RT group, serum superoxide dismutase levels in the α2M + RT group increased at the 1th day (P = 0.037), 14th day (P = 0.012), while reactive oxygen species levels clearly decreased at the 1th day (P< 0.001), 14th day (P = 0.007), and 28th day (P = 0.013). Conclusions A clinically translational model of jaw ORN was successfully established and the application of α2M prior to radiation protected the bone from being injured by the radiation, possibly related to oxidative stress.

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“…TMSCs have been tested in animal models of osteoporosis , osteoradinecrosis (ORN) , or calvarial defect and have demonstrated some promising outcomes as a feasible therapeutic treatment for bone‐related disorders (Table ). For example, tail injections of undifferentiated TMSCs or conditioned medium (CM) from TMSCs decreased the progression of osteoporosis in mice with BM depletion .…”

Section: Tonsil‐derived Mscs (Tmscs)mentioning

confidence: 99%

“…Similarly, the direct injection of undifferentiated TMSCs in proximal tibias of ovariecotmized (OVX) mice reduced the progression of osteoporosis . It is interesting to note that TMSCs themselves appear to have not only osteogenic but also wound healing properties even in the absence of induction from other osteogenic differentiation factors; the submucosal injection of undifferentiated TMSCs around the bone defect site decreased the risk of developing ORN caused by irradiation and tooth extraction in rats .…”

Section: Tonsil‐derived Mscs (Tmscs)mentioning

confidence: 99%

Application of Tonsil-Derived Mesenchymal Stem Cells in Tissue Regeneration: Concise Review

Choi

Kim

et al. 2019

Stem Cells

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Since the discovery of stem cells and multipotency characteristics of mesenchymal stem cells (MSCs), there has been tremendous development in regenerative medicine. MSCs derived from bone marrow have been widely used in various research applications, yet there are limitations such as invasiveness of obtaining samples, low yield and proliferation rate, and questions regarding their practicality in clinical applications. Some have suggested that MSCs from other sources, specifically those derived from palatine tonsil tissues, that is, tonsil-derived MSCs (TMSCs), could be considered as a new potential therapeutic tool in regenerative medicine due to their superior proliferation rate and differentiation capabilities with low immunogenicity and ease of obtaining. Several studies have determined that TMSCs have differentiation potential not only into the mesodermal lineage but also into the endodermal as well as ectodermal lineages, expanding their potential usage and placing them as an appealing option to consider for future studies in regenerative medicine. In this review, the differentiation capacities of TMSCs and their therapeutic competencies from past studies are addressed. STEM CELLS 2019;37:1252-1260 SIGNIFICANCE STATEMENTMesenchymal stem cells (MSCs) are considered as a great candidate for tissue engineering in regenerative medicine. Tonsil-derived MSCs (TMSCs) could be an attractive option for clinical applications because of their noninvasiveness of tissue collection, relatively high proliferation rate, and low allogenicity. This review addresses potential differentiation capabilities of TMSCs into mesodermal, endodermal, and ectodermal lineages reported from previous in vitro and in vivo studies as well as their potential applications for treating various human diseases.

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Preventive effects of tonsil‐derived mesenchymal stem cells on osteoradionecrosis in a rat model

Abstract: A single 20-Gy dose of irradiation combined with tooth extraction successfully generated ORN in the rat model. The tonsil-derived MSCs can be effective for bone regeneration in ORN, particularly when applied immediately after dentoalveolar trauma or surgery.

Cited by 20 publications

References 21 publications

The Supernatant of Tonsil-Derived Mesenchymal Stem Cell Has Antiallergic Effects in Allergic Rhinitis Mouse Model

The Supernatant of Tonsil-Derived Mesenchymal Stem Cell Has Antiallergic Effects in Allergic Rhinitis Mouse Model

Protective role of α2‐macroglobulin against jaw osteoradionecrosis in a preclinical rat model

Application of Tonsil-Derived Mesenchymal Stem Cells in Tissue Regeneration: Concise Review

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