BACKGROUND Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide,which emphasizes the urgent need to identify novel treatments.Stem cells from human exfoliated deciduous teet...BACKGROUND Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide,which emphasizes the urgent need to identify novel treatments.Stem cells from human exfoliated deciduous teeth(SHED),which are easy to obtain in a non-invasive manner,show pronounced proliferative and immunomodulatory capacities.AIM To investigate the protective effects of SHED on concanavalin A(ConA)-induced hepatitis in mice,and to elucidate the associated regulatory mechanisms.METHODS We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis,as well as the associated underlying mechanisms.RESULTS SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+,CD4+,tumor necrosis-alpha+,and interferon-gamma+inflammatory cells.Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice.SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations.Mechanistically,ConA upregulated tumor necrosisalpha and interferon-gamma expression,which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis,resulting in acute liver injury.SHED administration protected hepatocytes from ConA-induced apoptosis.CONCLUSION SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway.Our findings could provide a potential treatment strategy for hepatitis.展开更多
AIM: To investigate the effect of stem cells from human exfoliated deciduous teeth(SHED) transplanted for bone regeneration in the dog mandibular defect.METHODS: In this prospective comparative study, SHEDs had been i...AIM: To investigate the effect of stem cells from human exfoliated deciduous teeth(SHED) transplanted for bone regeneration in the dog mandibular defect.METHODS: In this prospective comparative study, SHEDs had been isolated 5 years ago from human exfoliated deciduous teeth. The undifferentiated stem cells were seeded into mandibular bone through-andthrough defects of 4 dogs. Similar defects in control group were filled with cell-free collagen scaffold. After 12 wk, biopsies were taken and morphometric analysis was performed. The percentage of new bone formation and foreign body reaction were measured in each case. The data were subject to statistical analysis using the Mann-Whitney U and Kruskalwalis statistical tests. Differences at P < 0.05 was considered as significant level.RESULTS: There were no significant differences between control and SHED-seeded groups in connective tissue(P = 0.248), woven bone(P = 0.248) and compact bone(P = 0.082). There were not any side effects in transplanted SHED group such as teratoma or malignancy and abnormalities in this period.CONCLUSION: SHEDs which had been isolated and characterized 5 years ago and stored with cryopreservation banking were capable of proliferation and osteogenesis after 5 years, and no immune response was observed after three months of seeded SHEDs.展开更多
Reference values reflecting the findings of natural concentrations of teeth in a well-defined group of individuals, are indispensable, if one is to interpret results generated for clinical utility. Hence, a comprehens...Reference values reflecting the findings of natural concentrations of teeth in a well-defined group of individuals, are indispensable, if one is to interpret results generated for clinical utility. Hence, a comprehensive compilation of literature survey is attempted to make available as a reference guideline for tooth element concentrations. Presently, the reference values are proposed for 19 elements. Several factors that are found influencing element levels, are common to any biosample and are broadly grouped under four categories namely, the factors of teeth, donor, environment and analytical methods. How best the influencing factors to be considered during analysis, are discussed. It is elucidated that standardized method of analysis with quality assurance and precision will reduce the ambiguity of comparison of inter-laboratory measurement. When the merits and demerits of element measurements are evaluated, it is recognized that except a hurdle of difficult specific sampling, many advantages make teeth an attractive material for environmental health monitoring of population and for assessment of element status of deficiency and excess due to differential exposure. The available data of tooth elements are lesser in comparison to data of blood and hair;further studies are required for reference values of others elements and for distribution pattern in different conditions, parts and types of teeth.展开更多
背景:人脱落乳牙牙髓干细胞具有较强的增殖和分化潜能,且具有较少的伦理争议和免疫排斥等优点,逐渐成为干细胞领域的研究热点。目的:总结近年来关于人乳牙牙髓干细胞分泌组的研究进展,探究其发挥治疗作用的分子机制,分析当前面临的问题...背景:人脱落乳牙牙髓干细胞具有较强的增殖和分化潜能,且具有较少的伦理争议和免疫排斥等优点,逐渐成为干细胞领域的研究热点。目的:总结近年来关于人乳牙牙髓干细胞分泌组的研究进展,探究其发挥治疗作用的分子机制,分析当前面临的问题并展望未来发展方向。方法:选择CNKI、PubMed数据库,中文检索词为“人脱落乳牙髓干细胞,间充质干细胞,分泌组,外泌体,条件培养基”;英文检索词为“stem cells from human exfoliated deciduous teeth,mesenchymal stem cells,secretome,exosome,conditioned medium”,初检获得文献642篇,选择近5年内的最新研究文献,以及近10年内影响因子超过5分的相关文献,由全体作者共同对检索文献进行评估,排除重复内容以及内容陈旧、相关性差的文献569篇,最终纳入73篇文献进行综述。结果与结论:人脱落乳牙牙髓干细胞因具备独特的生物学特性,近年来已成为组织工程与再生医学领域的重要研究对象。这类干细胞源自儿童生理性脱落的乳牙牙髓组织,具有多向分化潜能(如成骨、成神经、成血管等)、来源广泛且伦理争议小等显著优势。研究表明,人脱落乳牙牙髓干细胞不仅表现出比骨髓间充质干细胞更强的增殖能力,其免疫调节特性和低免疫原性更使它在骨组织修复、神经再生、牙周组织重建等领域展现出独特的临床应用价值。随着再生医学研究范式的转变,无细胞治疗策略的兴起为人脱落乳牙牙髓干细胞的应用开辟了新方向。无细胞治疗策略通过提取人脱落乳牙牙髓干细胞分泌组——包含外泌体、细胞因子、趋化因子、生长因子等多种生物活性物质的功能性组分,规避了传统活细胞移植中可能存在的细胞存活率低、免疫排斥反应及潜在致瘤性等风险。研究发现,人脱落乳牙牙髓干细胞分泌组可通过旁分泌机制介导血管生成、免疫调节、抗炎及抗凋亡等多重生物学效应,在肝损伤修复、心肌缺血治疗、骨缺损再生等动物模型中已展现出显著疗效。当前研究热点聚焦于通过工程化技术解析人脱落乳牙牙髓干细胞分泌组的分子组成,构建具有时空可控性的无细胞治疗体系。人脱落乳牙牙髓干细胞分泌组有望在精准医学框架下实现标准化生产与质量控制,为退行性疾病治疗和创伤修复提供创新解决方案。展开更多
目的探究神经表皮生长因子样蛋白1(Nel-like type 1 molecule,NELL-1)对人脱落乳牙牙髓干细胞(stem cells from human exfoliated deciduous teeth,SHEDs)增殖及骨向分化的影响。方法对SHEDs进行分离、培养和细胞鉴定,将生长状态良好的...目的探究神经表皮生长因子样蛋白1(Nel-like type 1 molecule,NELL-1)对人脱落乳牙牙髓干细胞(stem cells from human exfoliated deciduous teeth,SHEDs)增殖及骨向分化的影响。方法对SHEDs进行分离、培养和细胞鉴定,将生长状态良好的第3代细胞用于后续实验。SHEDs分为4组,分别加入浓度为0(对照组)、50、100、200 ng/mL的NELL-1,利用CCK-8法和结晶紫染色法检测细胞活性;碱性磷酸酶活性检测细胞成骨能力改变;RT-qPCR检测成骨相关基因ALP、OCN、Runx-2表达水平;Western blot法检测成骨相关蛋白ALP、Runx-2、Col-Ⅰ表达情况。结果SHEDs具有干细胞特性,50 ng/mL的NELL-1可显著促进SHEDs增殖(P<0.01);碱性磷酸酶活性检测结果显示,加入NELL-1后,各组细胞成骨效果优于对照组,其中50 ng/mL NELL-1组成骨效果最佳(P<0.05);RT-qPCR和Western blot结果显示50 ng/mL NELL-1显著促进ALP、OCN、Runx-2成骨相关基因及ALP、Runx-2、Col-Ⅰ蛋白表达(P<0.05)。结论NELL-1对SHEDs增殖、成骨分化具有促进作用。展开更多
基金Supported by The National Natural Science Foundation of China,No.81970940 and No.81600865Beijing Natural Science Foundation,No.7182182and the National Science and Technology Major Project of the Ministry of Science and Technology of China,No.2018ZX10302207.
文摘BACKGROUND Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide,which emphasizes the urgent need to identify novel treatments.Stem cells from human exfoliated deciduous teeth(SHED),which are easy to obtain in a non-invasive manner,show pronounced proliferative and immunomodulatory capacities.AIM To investigate the protective effects of SHED on concanavalin A(ConA)-induced hepatitis in mice,and to elucidate the associated regulatory mechanisms.METHODS We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis,as well as the associated underlying mechanisms.RESULTS SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+,CD4+,tumor necrosis-alpha+,and interferon-gamma+inflammatory cells.Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice.SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations.Mechanistically,ConA upregulated tumor necrosisalpha and interferon-gamma expression,which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis,resulting in acute liver injury.SHED administration protected hepatocytes from ConA-induced apoptosis.CONCLUSION SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway.Our findings could provide a potential treatment strategy for hepatitis.
文摘AIM: To investigate the effect of stem cells from human exfoliated deciduous teeth(SHED) transplanted for bone regeneration in the dog mandibular defect.METHODS: In this prospective comparative study, SHEDs had been isolated 5 years ago from human exfoliated deciduous teeth. The undifferentiated stem cells were seeded into mandibular bone through-andthrough defects of 4 dogs. Similar defects in control group were filled with cell-free collagen scaffold. After 12 wk, biopsies were taken and morphometric analysis was performed. The percentage of new bone formation and foreign body reaction were measured in each case. The data were subject to statistical analysis using the Mann-Whitney U and Kruskalwalis statistical tests. Differences at P < 0.05 was considered as significant level.RESULTS: There were no significant differences between control and SHED-seeded groups in connective tissue(P = 0.248), woven bone(P = 0.248) and compact bone(P = 0.082). There were not any side effects in transplanted SHED group such as teratoma or malignancy and abnormalities in this period.CONCLUSION: SHEDs which had been isolated and characterized 5 years ago and stored with cryopreservation banking were capable of proliferation and osteogenesis after 5 years, and no immune response was observed after three months of seeded SHEDs.
文摘Reference values reflecting the findings of natural concentrations of teeth in a well-defined group of individuals, are indispensable, if one is to interpret results generated for clinical utility. Hence, a comprehensive compilation of literature survey is attempted to make available as a reference guideline for tooth element concentrations. Presently, the reference values are proposed for 19 elements. Several factors that are found influencing element levels, are common to any biosample and are broadly grouped under four categories namely, the factors of teeth, donor, environment and analytical methods. How best the influencing factors to be considered during analysis, are discussed. It is elucidated that standardized method of analysis with quality assurance and precision will reduce the ambiguity of comparison of inter-laboratory measurement. When the merits and demerits of element measurements are evaluated, it is recognized that except a hurdle of difficult specific sampling, many advantages make teeth an attractive material for environmental health monitoring of population and for assessment of element status of deficiency and excess due to differential exposure. The available data of tooth elements are lesser in comparison to data of blood and hair;further studies are required for reference values of others elements and for distribution pattern in different conditions, parts and types of teeth.
文摘背景:人脱落乳牙牙髓干细胞具有较强的增殖和分化潜能,且具有较少的伦理争议和免疫排斥等优点,逐渐成为干细胞领域的研究热点。目的:总结近年来关于人乳牙牙髓干细胞分泌组的研究进展,探究其发挥治疗作用的分子机制,分析当前面临的问题并展望未来发展方向。方法:选择CNKI、PubMed数据库,中文检索词为“人脱落乳牙髓干细胞,间充质干细胞,分泌组,外泌体,条件培养基”;英文检索词为“stem cells from human exfoliated deciduous teeth,mesenchymal stem cells,secretome,exosome,conditioned medium”,初检获得文献642篇,选择近5年内的最新研究文献,以及近10年内影响因子超过5分的相关文献,由全体作者共同对检索文献进行评估,排除重复内容以及内容陈旧、相关性差的文献569篇,最终纳入73篇文献进行综述。结果与结论:人脱落乳牙牙髓干细胞因具备独特的生物学特性,近年来已成为组织工程与再生医学领域的重要研究对象。这类干细胞源自儿童生理性脱落的乳牙牙髓组织,具有多向分化潜能(如成骨、成神经、成血管等)、来源广泛且伦理争议小等显著优势。研究表明,人脱落乳牙牙髓干细胞不仅表现出比骨髓间充质干细胞更强的增殖能力,其免疫调节特性和低免疫原性更使它在骨组织修复、神经再生、牙周组织重建等领域展现出独特的临床应用价值。随着再生医学研究范式的转变,无细胞治疗策略的兴起为人脱落乳牙牙髓干细胞的应用开辟了新方向。无细胞治疗策略通过提取人脱落乳牙牙髓干细胞分泌组——包含外泌体、细胞因子、趋化因子、生长因子等多种生物活性物质的功能性组分,规避了传统活细胞移植中可能存在的细胞存活率低、免疫排斥反应及潜在致瘤性等风险。研究发现,人脱落乳牙牙髓干细胞分泌组可通过旁分泌机制介导血管生成、免疫调节、抗炎及抗凋亡等多重生物学效应,在肝损伤修复、心肌缺血治疗、骨缺损再生等动物模型中已展现出显著疗效。当前研究热点聚焦于通过工程化技术解析人脱落乳牙牙髓干细胞分泌组的分子组成,构建具有时空可控性的无细胞治疗体系。人脱落乳牙牙髓干细胞分泌组有望在精准医学框架下实现标准化生产与质量控制,为退行性疾病治疗和创伤修复提供创新解决方案。
