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
Dental stem cells can differentiate into different types of cells.Dental pulp stem cells,stem cells from human exfoliated deciduous teeth,periodontal ligament stem cells,stem cells from apical papilla,and dental folli...Dental stem cells can differentiate into different types of cells.Dental pulp stem cells,stem cells from human exfoliated deciduous teeth,periodontal ligament stem cells,stem cells from apical papilla,and dental follicle progenitor cells are five different types of dental stem cells that have been identified during different stages of tooth development.The availability of dental stem cells from discarded or removed teeth makes them promising candidates for tissue engineering.In recent years,three-dimensional(3D)tissue scaffolds have been used to reconstruct and restore different anatomical defects.With rapid advances in 3D tissue engineering,dental stem cells have been used in the regeneration of 3D engineered tissue.This review presents an overview of different types of dental stem cells used in 3D tissue regeneration,which are currently the most common type of stem cells used to treat human tissue conditions.展开更多
On all terms of pregnancy, insolvency of decidual reaction of endometrial cells is one of the reasons of miscarriages and fetal growth delay. The insufficient decidualization of endometrum leads to infertility in such...On all terms of pregnancy, insolvency of decidual reaction of endometrial cells is one of the reasons of miscarriages and fetal growth delay. The insufficient decidualization of endometrum leads to infertility in such pathologies, as Asherman’s syndrome and an endometrium atrophy. However, there are data on successful application of autologous bone marrow MSCs for Asherman’s syndrome treatment. The aim of this work was to assay the effect of endometrial mesenchymal stem cell (eMSC) transplantation for decidualization process in pseudopregnant rat. Our study showed that injection of human eMSC suspension into the uterine lumen of pseudopregnant rats facilitated more intensive development of decidua in comparison with phosphate buffed saline (PBS) injection in the control uterine horn. Histological analysis of decidua sections did not reveal any alterations in cell differentiation or tissue structure. In conclusion, we demonstrated for the first time that eMSC transplantation assists the development of all decidual tissue elements. It opens the possibility that eMSCs may be applied for cell therapy of infertility associated with decidualzation insufficiency.展开更多
目的:探讨肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)对人脱落乳牙牙髓干细胞(stem cells from human exfoliated deciduous teeth,SHED)骨分化能力的影响,分析ERK1/2-Runx2信号通路在该调控过程中的变化。方法:从6~8岁健康儿童...目的:探讨肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)对人脱落乳牙牙髓干细胞(stem cells from human exfoliated deciduous teeth,SHED)骨分化能力的影响,分析ERK1/2-Runx2信号通路在该调控过程中的变化。方法:从6~8岁健康儿童正常乳恒牙替换即将脱落的乳切牙中分离和培养SHED,取第三代细胞,分为对照组(成骨诱导剂培养)、观察组(成骨诱导剂和TNF-α共培养)和激动剂组(成骨诱导剂、TNF-α和ERK通路激动剂共培养)。采用茜素红染色评价成骨分化功能,采用Western印迹检测SHED细胞中Osterix、OPN、ERK1/2、pERK1/2和Runx2的蛋白表达水平,应用qRT-PCR检测Osterix、OPN、ERK1/2、pERK1/2和Runx2 mRNA的表达。采用SPSS 26.0软件包对数据进行统计学分析。结果:3组细胞成骨分化能力比较结果显示,3组细胞中均可见红棕色矿化结节。3组组间相比,对照组矿化结节最多,激动剂组次之,观察组最少。与对照组相比,观察组和激动剂组的Osterix、OPN蛋白和mRNA表达水平显著下降,而激动剂组Osterix、OPN蛋白和mRNA表达水平显著高于观察组;3组细胞的ERK1/2蛋白和mRNA表达水平无显著差异,而观察组和激动剂组pERK1/2和Runx2的蛋白和mRNA表达水平显著高于对照组,激动剂组的蛋白及mRNA表达水平显著高于观察组。结论:TNF-α对SHED成骨分化具有抑制作用,该作用可能与抑制ERK1/2-Runx2信号通路有关。展开更多
目的初步探索不同浓度骨碎补总黄酮(total flavone of rhizoma drynariae)对乳牙牙髓干细胞(stem cells from human exfoliated deciduous teeth)增殖及成骨分化能力的影响。方法2020年3月—2021年8月黑龙江省医院检验科初步筛选出适宜...目的初步探索不同浓度骨碎补总黄酮(total flavone of rhizoma drynariae)对乳牙牙髓干细胞(stem cells from human exfoliated deciduous teeth)增殖及成骨分化能力的影响。方法2020年3月—2021年8月黑龙江省医院检验科初步筛选出适宜浓度的RDTF,三代分离、培养SHEDs,通过流式细胞术及茜素红染色分别对细胞表面标志物和成骨分化潜能进行鉴定。实验分为4组(0时段为对照组,24、48、72 h组),每组设置3个复孔,采用不同浓度RDTF处理SHEDs后钙钴法染色,Western blot法检测其成骨相关蛋白表达情况。结果结果显示,所获取的细胞为具有成骨分化能力的SHEDs。与对照组相比,24、48、72 h内各浓度组均对SHEDs增殖无明显影响,差异无统计学意义(P>0.05),12.5、25 mg/L RDTF组的Runt相关转录因子2(Runx2)及骨钙素(OCN)的蛋白表达均显著上调,其中25 mg/L RDTF组对Runx2表达的促进效果最明显(249.681±14.653),差异有统计学意义(F=102.7,P<0.001)。结论RDTF对SHEDs的增殖无显著影响,可促进SHEDs成骨分化。展开更多
目的:利用RNA测序(RNA sequencing,RNA-seq)技术研究人脱落乳牙干细胞(stem cells derived from human exfoliated deciduous teeth,SHED)体外长时期扩增至20代(P20)后基因表达的差异,初步探讨其体外扩增衰老相关的信号通路。方法:从健...目的:利用RNA测序(RNA sequencing,RNA-seq)技术研究人脱落乳牙干细胞(stem cells derived from human exfoliated deciduous teeth,SHED)体外长时期扩增至20代(P20)后基因表达的差异,初步探讨其体外扩增衰老相关的信号通路。方法:从健康儿童脱落的乳牙中分离牙髓干细胞,在常规条件下将其扩增培养至20代,利用RNA-seq筛选出差异表达的基因,并对其进行相关生物学信息分析,寻找SHED体外连续扩增衰老相关的信号通路。结果:RNA-seq结果显示,SHED第4代(P4)和P20代差异表达的基因共有1884个,其中上调表达的基因有575个,下调表达基因1309个,这些差异表达的基因分布在生物过程(biological progress,BP)、细胞组成(cellular component,CC)和分子功能(molecular function,MF)等生物学过程中。早、晚期代次的SHED差异基因及相关蛋白之间的作用主要富集在剪接体、核糖体、细胞周期、p53通路相关的信号通路上。结论:本研究揭示了SHED体外连续扩增培养至第20代后基因表达谱的改变,为后续进一步研究其细胞体外衰老机制指明了方向。展开更多
To explore the possible mechanism of osteogenesis for deciduous teeth stem cells (DTSCs) in vivo/ vitro, stem cells from goat deciduous teeth (SGDs) were firstly isolated, induced and transplanted into immunocompromis...To explore the possible mechanism of osteogenesis for deciduous teeth stem cells (DTSCs) in vivo/ vitro, stem cells from goat deciduous teeth (SGDs) were firstly isolated, induced and transplanted into immunocompromised mice. The SGDs's mineralization pattern and osteogenesis were compared with bone marrow messenchymal stem cells (BMMSCs) from goats. SGDs have similar osteogenic differentiation pattern in vitro and bone-like tissue formation mechanism in vivo to BMMSCs; moreover SGDs have stronger alkaline phosphatase (ALP) gene expression and osteopontin (OPN) gene expression levels than BMMSCs; also SGDs can form more bone-like tissues than BMMSCs when cell-scaffold compounds are transplanted into immunocompromised mice. This pre-clinical study in a large-animal model confirms that DTSCs may be an appropriate source of stem cells in repairing bone defects with tissue engineering.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.
基金Supported by Chang Gung Memorial Hospital,Linkou,Taiwan,No.CORPG3K0021 and No.CORPG3K0191.
文摘Dental stem cells can differentiate into different types of cells.Dental pulp stem cells,stem cells from human exfoliated deciduous teeth,periodontal ligament stem cells,stem cells from apical papilla,and dental follicle progenitor cells are five different types of dental stem cells that have been identified during different stages of tooth development.The availability of dental stem cells from discarded or removed teeth makes them promising candidates for tissue engineering.In recent years,three-dimensional(3D)tissue scaffolds have been used to reconstruct and restore different anatomical defects.With rapid advances in 3D tissue engineering,dental stem cells have been used in the regeneration of 3D engineered tissue.This review presents an overview of different types of dental stem cells used in 3D tissue regeneration,which are currently the most common type of stem cells used to treat human tissue conditions.
文摘On all terms of pregnancy, insolvency of decidual reaction of endometrial cells is one of the reasons of miscarriages and fetal growth delay. The insufficient decidualization of endometrum leads to infertility in such pathologies, as Asherman’s syndrome and an endometrium atrophy. However, there are data on successful application of autologous bone marrow MSCs for Asherman’s syndrome treatment. The aim of this work was to assay the effect of endometrial mesenchymal stem cell (eMSC) transplantation for decidualization process in pseudopregnant rat. Our study showed that injection of human eMSC suspension into the uterine lumen of pseudopregnant rats facilitated more intensive development of decidua in comparison with phosphate buffed saline (PBS) injection in the control uterine horn. Histological analysis of decidua sections did not reveal any alterations in cell differentiation or tissue structure. In conclusion, we demonstrated for the first time that eMSC transplantation assists the development of all decidual tissue elements. It opens the possibility that eMSCs may be applied for cell therapy of infertility associated with decidualzation insufficiency.
基金the Science and Technology Commission fund of Shanghai Municipality (No. 09JC1411700)the Collaboration Projects of Development and Research from Basic Science of Stomatology of Shanghai(No. S30206-KF09)the Fund of Shanghai Jiaotong University School of Medicine (No. 09XJ21030)
文摘To explore the possible mechanism of osteogenesis for deciduous teeth stem cells (DTSCs) in vivo/ vitro, stem cells from goat deciduous teeth (SGDs) were firstly isolated, induced and transplanted into immunocompromised mice. The SGDs's mineralization pattern and osteogenesis were compared with bone marrow messenchymal stem cells (BMMSCs) from goats. SGDs have similar osteogenic differentiation pattern in vitro and bone-like tissue formation mechanism in vivo to BMMSCs; moreover SGDs have stronger alkaline phosphatase (ALP) gene expression and osteopontin (OPN) gene expression levels than BMMSCs; also SGDs can form more bone-like tissues than BMMSCs when cell-scaffold compounds are transplanted into immunocompromised mice. This pre-clinical study in a large-animal model confirms that DTSCs may be an appropriate source of stem cells in repairing bone defects with tissue engineering.
