The relationship between commensal bacteria and the epithelial cells lining the colon is normally symbiotic. However, in the setting of diseases which lead to a loss of the protective mucosal layer such as inflammator...The relationship between commensal bacteria and the epithelial cells lining the colon is normally symbiotic. However, in the setting of diseases which lead to a loss of the protective mucosal layer such as inflammatory bowel disease or colon cancer, commensal bacteria gain the ability to alter both the behavior of epithelial cells as well as their surrounding extra cellular matrix (ECM). While much work has been done to understand the effects of bacteria on diseased epithelial cells in the colon, very little has been done to understand their impact on the ECM. In our previous work, we have shown that topographical changes in the ECM on the luminal side of the colon have a profound influence on the behavior of colonic epithelial cells. However, we do not understand all of the mechanisms that lead to changes in the ECM topography. This study aimed to understand the role that commensal E. coli strains play in altering the ECM topography of type-1 collagen scaffolds. To do this, 1.2 mg/ml type 1 collagen scaffolds were infected with various commensal bacterial strains. At 24 hours post-infection collagen fiber dimensions and substrate topography were determined using standard molecular biology techniques and advanced imaging. Intriguingly, all of the commensal E. coli strains showed some form of substrate degradation. Especially in the case of commensal E. coli strain HS4, maximum nano-scaled protrusions were observed. This data suggests, for the first time, that studying the effects of bacteria alone on the ECM may be critical to improving our understanding of how the cellular microenvironment changes in both health and disease.展开更多
The tumor ecosystem with heterogeneous cellularcompositions and the tumor microenvironment has increasingly become the focus of cancer research in recent years. Theextracellular matrix (ECM), the major component of t...The tumor ecosystem with heterogeneous cellularcompositions and the tumor microenvironment has increasingly become the focus of cancer research in recent years. Theextracellular matrix (ECM), the major component of the tumor microenvironment, and its interactions with the tumorcells and stromal cells have also enjoyed tremendouslyincreased attention. Like the other components of the tumormicroenvironment, the ECM in solid tumors differs significantly from that in normal organs and tissues. We reviewrecent studies of the complex roles the tumor ECM plays incancer progression, from tumor initiation, growth to angiogenesis and invasion. We highlight that the biomolecular,biophysical, and mechanochemical interactions between theECM and cells not only regulate the steps of cancer progression, but also affect the efficacy of systemic cancer treatment.We further discuss the strategies to target and modify thetumor ECM to improve cancer therapy.展开更多
目的可吸收生物材料聚羟乙酸(PGA)与成纤维细胞已被证实可以应用于体外组织工程肌腱的构建,本试验旨在探讨应用人皮肤成纤维细胞与PGA在体外进行组织构建时的适宜接种浓度。方法酶消化法获得人皮肤成纤维细胞经体外培养、扩增至第2代,...目的可吸收生物材料聚羟乙酸(PGA)与成纤维细胞已被证实可以应用于体外组织工程肌腱的构建,本试验旨在探讨应用人皮肤成纤维细胞与PGA在体外进行组织构建时的适宜接种浓度。方法酶消化法获得人皮肤成纤维细胞经体外培养、扩增至第2代,按照低、中、高三种浓度接种于PGA材料分别作为实验组1、2、3,传统浓度细胞接种的作为对照组,各组样本数n均为3,分别于接种后3天、1周、2周和4周进行观察和检测。结果接种后3天实验各组无明显差异,细胞在材料上黏附伸展良好。1周和2周时,各组细胞均有明显增殖,并分泌细胞外基质(ECM extra cellular matrix),但实验组1、2的ECM不如实验组3和对照组丰富,此后该现象更为明显。至第4周时,实验组1仅形成厚薄不均的薄膜状物,其余三组均形成组织样结构,但实验组2形成的细胞--材料复合物结构略为松散。结论应用本实验组中高浓度接种皮肤成纤维细胞在体外构建工程化组织可以达到传统所用更高浓度的接种效果,以节约细胞,减少取材。展开更多
目的:观察黄芪、太子参对大鼠肾小球系膜细胞基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)及基质金属蛋白酶抑制剂-2(tissue inhibitor of metalloproteinase-2,TIMP-2)-mRNA表达的影响。探讨黄芪、太子参对肾小球硬化的防治作...目的:观察黄芪、太子参对大鼠肾小球系膜细胞基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)及基质金属蛋白酶抑制剂-2(tissue inhibitor of metalloproteinase-2,TIMP-2)-mRNA表达的影响。探讨黄芪、太子参对肾小球硬化的防治作用。方法:(1)应用血清药理学方法,制取中药的药理血清。(2)采用血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)作为刺激因子,培养大鼠肾小球系膜细胞,使其发生增殖。(3)应用反转录多聚酶链反应技术(RT-PCR)观察各组间MMP-2及TIMP-2m-RNA表达的情况。结果:黄芪、太子参对TIMP-2有显著地抑制作用,与对照组比较差异有统计学意义(P<0.05)。对MMP-2的影响差异无统计学意义。结论:黄芪、太子参通过抑制TIMP-2的基因表达,从而达到延缓肾小球硬化的作用。展开更多
文摘The relationship between commensal bacteria and the epithelial cells lining the colon is normally symbiotic. However, in the setting of diseases which lead to a loss of the protective mucosal layer such as inflammatory bowel disease or colon cancer, commensal bacteria gain the ability to alter both the behavior of epithelial cells as well as their surrounding extra cellular matrix (ECM). While much work has been done to understand the effects of bacteria on diseased epithelial cells in the colon, very little has been done to understand their impact on the ECM. In our previous work, we have shown that topographical changes in the ECM on the luminal side of the colon have a profound influence on the behavior of colonic epithelial cells. However, we do not understand all of the mechanisms that lead to changes in the ECM topography. This study aimed to understand the role that commensal E. coli strains play in altering the ECM topography of type-1 collagen scaffolds. To do this, 1.2 mg/ml type 1 collagen scaffolds were infected with various commensal bacterial strains. At 24 hours post-infection collagen fiber dimensions and substrate topography were determined using standard molecular biology techniques and advanced imaging. Intriguingly, all of the commensal E. coli strains showed some form of substrate degradation. Especially in the case of commensal E. coli strain HS4, maximum nano-scaled protrusions were observed. This data suggests, for the first time, that studying the effects of bacteria alone on the ECM may be critical to improving our understanding of how the cellular microenvironment changes in both health and disease.
基金This work was partially supported by the National Institute of Health grants from NCI(R01CA201340)NEI(1R01EY028450).
文摘The tumor ecosystem with heterogeneous cellularcompositions and the tumor microenvironment has increasingly become the focus of cancer research in recent years. Theextracellular matrix (ECM), the major component of the tumor microenvironment, and its interactions with the tumorcells and stromal cells have also enjoyed tremendouslyincreased attention. Like the other components of the tumormicroenvironment, the ECM in solid tumors differs significantly from that in normal organs and tissues. We reviewrecent studies of the complex roles the tumor ECM plays incancer progression, from tumor initiation, growth to angiogenesis and invasion. We highlight that the biomolecular,biophysical, and mechanochemical interactions between theECM and cells not only regulate the steps of cancer progression, but also affect the efficacy of systemic cancer treatment.We further discuss the strategies to target and modify thetumor ECM to improve cancer therapy.
文摘目的可吸收生物材料聚羟乙酸(PGA)与成纤维细胞已被证实可以应用于体外组织工程肌腱的构建,本试验旨在探讨应用人皮肤成纤维细胞与PGA在体外进行组织构建时的适宜接种浓度。方法酶消化法获得人皮肤成纤维细胞经体外培养、扩增至第2代,按照低、中、高三种浓度接种于PGA材料分别作为实验组1、2、3,传统浓度细胞接种的作为对照组,各组样本数n均为3,分别于接种后3天、1周、2周和4周进行观察和检测。结果接种后3天实验各组无明显差异,细胞在材料上黏附伸展良好。1周和2周时,各组细胞均有明显增殖,并分泌细胞外基质(ECM extra cellular matrix),但实验组1、2的ECM不如实验组3和对照组丰富,此后该现象更为明显。至第4周时,实验组1仅形成厚薄不均的薄膜状物,其余三组均形成组织样结构,但实验组2形成的细胞--材料复合物结构略为松散。结论应用本实验组中高浓度接种皮肤成纤维细胞在体外构建工程化组织可以达到传统所用更高浓度的接种效果,以节约细胞,减少取材。
文摘目的:观察黄芪、太子参对大鼠肾小球系膜细胞基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)及基质金属蛋白酶抑制剂-2(tissue inhibitor of metalloproteinase-2,TIMP-2)-mRNA表达的影响。探讨黄芪、太子参对肾小球硬化的防治作用。方法:(1)应用血清药理学方法,制取中药的药理血清。(2)采用血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)作为刺激因子,培养大鼠肾小球系膜细胞,使其发生增殖。(3)应用反转录多聚酶链反应技术(RT-PCR)观察各组间MMP-2及TIMP-2m-RNA表达的情况。结果:黄芪、太子参对TIMP-2有显著地抑制作用,与对照组比较差异有统计学意义(P<0.05)。对MMP-2的影响差异无统计学意义。结论:黄芪、太子参通过抑制TIMP-2的基因表达,从而达到延缓肾小球硬化的作用。
