Language：Japanese   Publisher：Scientific Reports  

Alveolar bone loss caused by periodontal disease eventually leads to tooth loss. Periodontal ligament stem cells (PDLSCs) are the tissue-specific cells for maintaining and repairing the periodontal ligament, cementum, and alveolar bone. Here, we investigated the role of erythropoietin receptor (EPOR), which regulates the microenvironment-modulating function of mesenchymal stem cells, in PDLSC-based periodontal therapy. We isolated PDLSCs from patients with chronic periodontal disease and healthy donors, referred to as PD-PDLSCs and Cont-PDLSCs, respectively. PD-PDLSCs exhibited reduced potency of periodontal tissue regeneration and lower expression of EPOR compared to Cont-PDLSCs. EPOR-silencing suppressed the potency of Cont-PDLSCs mimicking PD-PDLSCs, whereas EPO-mediated EPOR activation rejuvenated the reduced potency of PD-PDLSCs. Furthermore, we locally transplanted EPOR-silenced and EPOR-activated PDLSCs into the gingiva around the teeth of ligament-induced periodontitis model mice and demonstrated that EPOR in PDLSCs participated in the regeneration of the periodontal ligament, cementum, and alveolar bone in the ligated teeth. The EPOR-mediated paracrine function of PDLSCs maintains periodontal immune suppression and bone metabolic balance via osteoclasts and osteoblasts in the periodontitis model mice. Taken together, these results suggest that EPOR signaling is crucial for PDLSC-based periodontal regeneration and paves the way for the development of novel options for periodontal therapy.

DOI： 10.1038/s41598-024-57361-y

Scopus

PubMed

Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞ここがポイント　乳歯の萠出には個人差がある.乳歯の早期脱落は全身疾患との関連に注意が必要である.乳歯のエナメル形成不全は永久歯にも生じることがある.

Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Company of Biologists  

Non-excitable cells express sodium voltage-gated channel alpha subunit 1 gene and protein (SCN1A/NaV1.1); however, the functions of NaV1.1 are unclear. SCN1A was expressed in human mesenchymal stem cells (MSCs). Nav1.1 was abundantly expressed in the endoplasmic reticulum of MSCs; however, its expression was not found to be related to sodium currents. SCN1A-silencing reduced MSC proliferation and delayed the cell cycle in the S phase. SCN1A-silencing also suppressed the protein levels of CDK2 and AKT, despite similar mRNA expression, and inhibited AKT phosphorylation in MSCs. Cycloheximide-chase assay showed that SCN1A-silencing induced CDK2 but not AKT protein degradation in MSCs. Proteolysis inhibition assay using epoxomicin, bafilomycin A1, and NH4Cl, revealed that the ubiquitin-proteasome and autophagy/endo-lysosome systems were irrelevant to CDK2 and AKT protein reduction in SCN1A-silenced MSCs. AKT inhibitor LY294002 did not affect the degradation and nuclear localization of CDK2 in MSCs. Likewise, AKT activator SC79 did not attenuate the SCN1A-silencing effects on CDK2 in MSCs. These results suggest that NaV1.1 contributes to the cell cycle of MSCs by regulating the post-translational control of AKT and CDK2.

DOI： 10.1242/jcs.261732

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Hirschsprung disease (HSCR) and its associated disorders (AD-HSCR) often result in severe hypoperistalsis caused by enteric neuropathy, mesenchymopathy, and myopathy. Notably, HSCR involving the small intestine, isolated hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction, and megacystis-microcolon-intestinal hypoperistalsis syndrome carry a poor prognosis. Ultimately, small-bowel transplantation (SBTx) is necessary for refractory cases, but it is highly invasive and outcomes are less than optimal, despite advances in surgical techniques and management. Thus, regenerative therapy has come to light as a potential form of treatment involving regeneration of the enteric nervous system, mesenchyme, and smooth muscle in affected areas. We review the cutting-edge regenerative therapeutic approaches for managing HSCR and AD-HSCR, including the use of enteric nervous system progenitor cells, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells as cell sources, the recipient intestine's microenvironment, and transplantation methods. Perspectives on the future of these treatments are also discussed.

DOI： 10.1007/s00595-023-02741-6

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PubMed

Language：English  

Alveolar bone loss caused by periodontal disease eventually leads to tooth loss. Periodontal ligament stem cells (PDLSCs) are the tissue-specific cells for maintaining and repairing the periodontal ligament, cementum, and alveolar bone. Here, we investigated the role of erythropoietin receptor (EPOR), which regulates the microenvironment-modulating function of mesenchymal stem cells, in PDLSC-based periodontal therapy. We isolated PDLSCs from patients with chronic periodontal disease and healthy donors, referred to as PD-PDLSCs and Cont-PDLSCs, respectively. PD-PDLSCs exhibited reduced potency of periodontal tissue regeneration and lower expression of EPOR compared to Cont-PDLSCs. EPOR-silencing suppressed the potency of Cont-PDLSCs mimicking PD-PDLSCs, whereas EPO-mediated EPOR activation rejuvenated the reduced potency of PD-PDLSCs. Furthermore, we locally transplanted EPOR-silenced and EPOR-activated PDLSCs into the gingiva around the teeth of ligament-induced periodontitis model mice and demonstrated that EPOR in PDLSCs participated in the regeneration of the periodontal ligament, cementum, and alveolar bone in the ligated teeth. The EPOR-mediated paracrine function of PDLSCs maintains periodontal immune suppression and bone metabolic balance via osteoclasts and osteoblasts in the periodontitis model mice. Taken together, these results suggest that EPOR signaling is crucial for PDLSC-based periodontal regeneration and paves the way for the development of novel options for periodontal therapy.

CiNii Research

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.molmet.2022.101599

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PubMed

Language：English   Publisher：(一社)歯科基礎医学会  

チャンバー内細胞培養系を用いて歯原性間葉系細胞のサブセットが歯原性上皮細胞からエナメル芽細胞への分化に重要であることを発見した。歯髄細胞からGSK3β阻害剤BIOを用いて歯髄幹細胞様細胞を誘導し、歯髄幹細胞により誘導されるエナメル芽細胞分化のメカニズムについて検討した。BIOで誘導された歯髄細胞は間葉系幹細胞マーカーOct3/4およびBcrp1を高発現した。BIOで誘導された人工歯髄幹細胞を用いて、歯髄幹細胞に発現するエナメル芽細胞分化に必要な分子を同定した。歯原性上皮細胞との相互作用を介して歯髄幹細胞でPanx3発現が誘導された。さらにPanx3発現細胞でATP遊離が増加した。ATP刺激は歯原性上皮細胞に受容された。以上の結果から、歯髄幹細胞に発現するPanx3がエナメル芽細胞分化に重要で、Panx3によるATP遊離が上皮間葉系相互作用に寄与すると考えられた。

Language：Japanese   Publisher：Journal of Oral Biosciences  

Objectives: Epithelial-mesenchymal interactions are extremely important in tooth development and essential for ameloblast differentiation, especially during tooth formation. We aimed to identify the type of mesenchymal cells important in ameloblast differentiation. Methods: We used two types of cell culture systems with chambers and found that a subset of debtal mesenchimal cells is important for the differentiatiuon of dental spithelial cells into ameloblasts. Further, we induced dental pulp stem cell-like cells from dental pulp stem cells using the small molecule compound BIO ( a GSK-3 inhibitor IX) to clarify the mechanism involved in ameloblast differentiation induced by dental pulp stem cells. Results: The BIO-induced dental pulp cells promoted the expression of mesenchymal stem cell markers Oct3/4 and Bcrp1. Furthermore, we used artificial dental pulp stem cells induced by BIO to identify the molecules expressed in dental pulp stem cells required for ameloblast differentiation. Panx3 expression was induced in the dental pulp stem cell through interaction with the dental epithelial cells. In addition, ATP release from cells increased in Panx3-expressing cells. We also confirmed that ATP stimulation is accepted in dental epithelial cells. Conclusions: These results showed that the Panx3 expressed in dental pulp stem cells is important for ameloblast differentiation and that ATP release by Panx3 may play a role in epithelial–mesenchymal interaction.

DOI： 10.1016/j.job.2022.10.002

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.xpro.2022.101386

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.pdj.2021.11.002

Scopus

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publisher：(公社)日本小児歯科学会  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title><sec>
<title>Background</title>
Stem cells from human exfoliated deciduous teeth (SHED) have been reported to show the in vivo and in vitro hepatic differentiation, SHED-Heps; however, the cholangiogenic potency of SHED-Heps remains unclear. Here, we hypothesized that SHED-Heps contribute to the regeneration of intrahepatic bile duct system in chronic fibrotic liver.


</sec><sec>
<title>Methods</title>
SHED were induced into SHED-Heps under cytokine stimulation. SHED-Heps were intrasplenically transplanted into chronically CCl₄-treated liver fibrosis model mice, followed by the analysis of donor integration and hepatobiliary metabolism in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile duct system in the recipient liver. Furthermore, SHED-Heps were induced under the stimulation of tumor necrosis factor alpha (TNFA).


</sec><sec>
<title>Results</title>
The intrasplenic transplantation of SHED-Heps into CCl₄-treated mice showed that donor SHED-Heps behaved as human hepatocyte paraffin 1- and human albumin-expressing hepatocyte-like cells in situ and ameliorated CCl₄-induced liver fibrosis. Of interest, the integrated SHED-Heps not only expressed biliary canaliculi ATP-binding cassette transporters including ABCB1, ABCB11, and ABCC2, but also recruited human keratin 19- (KRT19-) and KRT17-positive cells, which are considered donor-derived cholangiocytes, regenerating the intrahepatic bile duct system in the recipient liver. Furthermore, the stimulation of TNFA induced SHED-Heps into KRT7- and SRY-box 9-positive cells.


</sec><sec>
<title>Conclusions</title>
Collectively, our findings demonstrate that infused SHED-Heps showed cholangiogenic ability under the stimulation of TNFA in CCl₄-damaged livers, resulting in the regeneration of biliary canaliculi and interlobular bile ducts in chronic fibrotic liver. Thus, the present findings suggest that SHED-Heps may be a novel source for the treatment of cholangiopathy.


</sec>

DOI： 10.1186/s13287-020-02113-8

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PubMed

Other Link： http://link.springer.com/article/10.1186/s13287-020-02113-8/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)  

Background: Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated. Current surgical options, including Kasai hepatoportoenterostomy and orthotopic liver organ transplantations, are palliative; thus, innovation in BA therapy is urgent. / Methods: To examine whether BA-specific post-natal stem cells are feasible for autologous cell source for BA treatment, we isolated from human exfoliated deciduous teeth, namely BA-SHED, using a standard colony-forming unit fibroblast (CFU-F) method and compared characteristics as mesenchymal stem cells (MSCs) to healthy donor-derived control SHED, Cont-SHED. BA-SHED and Cont-SHED were intrasplenically transplanted into chronic carbon tetrachloride ( CCl4)-induced liver fibrosis model mice, followed by the analysis of bile drainage function and donor integration in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile ducts in the recipient’s liver using anti-human specific keratin 19 (KRT19) antibody. / Results: BA-SHED formed CFU-F, expressed MSC surface markers, and exhibited in vitro mesenchymal multipotency similar to Cont-SHED. BA-SHED showed less in vitro hepatogenic potency than Cont-SHED. Cont-SHED represented in vivo bile drainage function and KRT19-positive biliary regeneration in chronic carbon tetrachloride-induced liver fibrosis model mice. BA-SHED failed to show in vivo biliary potency and bile drainage function compared to Cont-SHED. / Conclusion: These findings indicate that BA-SHED are not feasible source for BA treatment, because BA-SHED may epigenetically modify the underlying prenatal and perinatal BA environments. In conclusion, these findings suggest that BA-SHED-based studies may provide a platform for understanding the underlying molecular mechanisms of BA development and innovative novel modalities in BA research and treatment.

DOI： 10.1186/s13287-021-02652-8

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PubMed

CiNii Research

Publisher：金原出版  

DOI： 10.18888/sh.0000001871

CiNii Research

Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞POINT　こんな時は要治療 小児のブラキシズムは内服薬や睡眠障害を含む全身疾患と関連する場合は,専門医での治療が必要になる.また,歯の咬耗による違和感や疼痛,歯列不正との関連がある場合は,歯科医院での治療が必要になる.歯科医院でのブラキシズムへのアプローチの一つとして,マウスピース(図4)を使用することがあり,歯科医院での作製と管理が必要となる.こんな時は経過観察 小児のブラキシズムの発生頻度は高いが,他の口腔習癖と同様に無意識で起こる異常習癖であり,年齢とともに自然消失することも多いので,基本的に経過観察となる.子どもの歯ぎしりに不安をもつ保護者は多いことから,以上のことをふまえて子どもや母親に寄り添いながら経過観察を行うことが重要である.

Language：Japanese   Publishing type：Research paper (scientific journal)  

Systemic transplantation of stem cells from human exfoliated deciduous teeth (SHED) is used to treat systemic lupus erythematosus (SLE)-like disorders in MRL/lpr mice. However, the mechanisms underlying the SHED-based therapy remain unclear. In this study, we hypothesized that trophic factors within SHED-releasing extracellular vesicles (SHED-EVs) ameliorate the SLE-like phenotypes in MRL/lpr mice. SHED-EVs were isolated from the culture supernatant of SHED. SHED-EVs were treated with or without RNase and systemically administered to MRL/lpr mice. Subsequently, recipient bone marrow mesenchymal stem cells (BMMSCs) isolated from SHED-EV-administered MRL/lpr mice were examined for the in vitro and in vivo activity of hematopoietic niche formation and immunoregulation. Furthermore, the recipient BMMSCs were secondarily transplanted into MRL/lpr mice. The systemic SHED-EV infusion ameliorated the SLE-like phenotypes in MRL/lpr mice and improved the functions of recipient BMMSCs by rescuing Tert mRNA-associated telomerase activity, hematopoietic niche formation, and immunoregulation. The secondary transplantation of recipient BMMSCs recovered the immune condition and renal functions of MRL/lpr mice. The RNase treatment depleted RNAs, such as microRNAs, within SHED-EVs, and the RNA-depleted SHED-EVs attenuated the benefits of SHED-EVs in MRL/lpr mice. Collectively, our findings suggest that SHED-secreted RNAs, such as microRNAs, play a crucial role in treating SLE by targeting the telomerase activity of recipient BMMSCs.

DOI： 10.4049/jimmunol.2001312

Scopus

PubMed

Language：Japanese   Publisher：(公社)日本小児歯科学会  

教育問題検討委員会では、全国29歯科大学・大学歯学部の小児歯科学の講義を担当する講座を対象に、平成30年度版歯科医師国家試験出題基準の小児歯科学分野における必修の基本事項、歯科医学総論および各論の大・中・小項目の内容に関してのアンケート調査を行った。調査の結果、現状の必修および歯科医学総論の出題基準には、少なからず問題のあることがわかった。歯科医学各論に関しては、必修や総論に比べ、より具体性の高い出題基準になっていることが窺われた。必修・歯科医学総論および各論において、各々の小項目の記載がない中項目(以下、中項目とする)および小項目が小児歯科学分野の国家試験出題基準に該当するかの問いに対しては、「該当する」との回答が50%未満の中項目あるいは小項目が50%以上を占める大項目が多数認められた。(著者抄録)

Language：Japanese   Publishing type：Research paper (scientific journal)  

A subpopulation of mesenchymal stem cells, developmentally derived from multipotent neural crest cells that form multiple facial tissues, resides within the dental pulp of human teeth. These stem cells show high proliferative capacity in vitro and are multipotent, including adipogenic, myogenic, osteogenic, chondrogenic, and neurogenic potential. Teeth containing viable cells are harvested via minimally invasive procedures, based on various clinical diagnoses, but then usually discarded as medical waste, indicating the relatively low ethical considerations to reuse these cells for medical applications. Previous studies have demonstrated that stem cells derived from healthy subjects are an excellent source for cell-based medicine, tissue regeneration, and bioengineering. Furthermore, stem cells donated by patients affected by genetic disorders can serve as in vitro models of disease-specific genetic variants, indicating additional applications of these stem cells with high plasticity. This review discusses the benefits, limitations, and perspectives of patient-derived dental pulp stem cells as alternatives that may complement other excellent, yet incomplete stem cell models, such as induced pluripotent stem cells, together with our recent data.

DOI： 10.3390/ijms22052269

Scopus

PubMed

Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞POINT　こんな時は要治療 小児のブラキシズムは内服薬や睡眠障害を含む全身疾患と関連する場合は,専門医での治療が必要になる.また,歯の咬耗による違和感や疼痛,歯列不正との関連がある場合は,歯科医院での治療が必要になる.歯科医院でのブラキシズムへのアプローチの一つとして,マウスピース(図4)を使用することがあり,歯科医院での作製と管理が必要となる.こんな時は経過観察 小児のブラキシズムの発生頻度は高いが,他の口腔習癖と同様に無意識で起こる異常習癖であり,年齢とともに自然消失することも多いので,基本的に経過観察となる.子どもの歯ぎしりに不安をもつ保護者は多いことから,以上のことをふまえて子どもや母親に寄り添いながら経過観察を行うことが重要である.

Language：Japanese  

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