BACKGROUND Multinucleated giant cells(MGCs)in bladder carcinomas are poorly studied.AIM To describe the function,morphogenesis,and origin of mononuclear and MGCs in urothelial carcinoma(UC)of the bladder in Bulgarian ...BACKGROUND Multinucleated giant cells(MGCs)in bladder carcinomas are poorly studied.AIM To describe the function,morphogenesis,and origin of mononuclear and MGCs in urothelial carcinoma(UC)of the bladder in Bulgarian and French patients.METHODS Urothelial bladder carcinomas(n=104)from 2016-2020 were analyzed retrospectively using immunohistochemical(IHC)and histochemical stain examination.Giant cells in the bladder stroma were found in 35.6%of cases,more often in highgrades.RESULTS We confirm that MGCs in the mucosa in UC of the bladder were positive for both mesenchymal and myofibroblast markers(vimentin,smooth muscle actin,Desmin,and CD34)and the macrophage marker CD68.Furthermore,IHC studies revealed the following profile of these cells:Positive for p16;negative for epithelial(CK AE1/AE3 and GATA-3),vascular(CD31),neural(PS100 and CKIT),cambial,blastic(CD34-blasts and C-KIT),and immune markers(IG G,immunoglobulin G4,and PD-L1);no proliferative activity,possess no specific immune function,and cannot be used to calculate the Combined Positive Score scale.CONCLUSION In conclusion,the giant stromal cells in non-tumor and tumor bladder can be used as a characteristic and relatively constant,although nonspecific,histological marker for chronic bladder damage,reflecting the chronic irritation or inflammation.Likewise,according to the morphological and IHC of the mono-and multinucleated giant cells in the bladder,they are most likely represent telocytes capable of adapting their morphology to the pathology of the organ.展开更多
Myocardial infarction(MI)is a disorder that lowers the lifespan and quality of life.Reperfusion treatment as early as possible is the most effective solution,with an increased focus on post-MI medication.In the recove...Myocardial infarction(MI)is a disorder that lowers the lifespan and quality of life.Reperfusion treatment as early as possible is the most effective solution,with an increased focus on post-MI medication.In the recovery process after MI,telocytes(TCs)appear to play an important role,which develops a large number of questions awaiting answers.Defining possible signaling mechanisms involved in recovery after MI may lead to identification the limits of current therapies,and development of new therapeutic solutions.Key words:telocytes;myocardial infarction;stem展开更多
Telocytes (TCs) are a novel type of interstitial cells that are thought to be involved in tissue regeneration and repair. However, the possible roles of TCs in vascular diseases remain unclear. In this study, we use...Telocytes (TCs) are a novel type of interstitial cells that are thought to be involved in tissue regeneration and repair. However, the possible roles of TCs in vascular diseases remain unclear. In this study, we used a rat model of carotid artery balloon injury (CABI) to study the changes and potential roles of vascular TCs after vascular injury. Transmission electron microscopy (TEM) and CD34/vimentin immunolabeling were used to identify and quantify TCs in normal and injured carotid arteries. Quantita- tive immunofluorescence analysis revealed that, compared with the sham group, the number of TCs in the CAB1 group in- creased from 7.2+1.0 to an average of 20.4+1.8 per l-ram2 vascular area. The expression level of miR-24 in TCs was three times higher than in vascular smooth muscle cells (VSMCs). The percentage of VSMCs in S phase and G2/M phase increased by approximately 5% when VSMCs were incubated with the supematant of TCs. The antagomir of miR-24 in TCs reduced the ratio of VSMCs in S ohase and G2/M phase. This study illuminates the function of TCs in the proliferation of VSMCs.展开更多
Interstitial Cajal-like cells are a distinct type of interstitial cell with a wide distribution in mammalian organs and tissues,and have been given the name"telocytes".Recent studies have demonstrated the po...Interstitial Cajal-like cells are a distinct type of interstitial cell with a wide distribution in mammalian organs and tissues,and have been given the name"telocytes".Recent studies have demonstrated the potential roles of telocytes in heart development,renewal,and repair.However,further research on the functions of telocytes is limited by the complicated in vivo environment.This study was designed to construct engineered heart tissue(EHT)as a three-dimensional model in vitro to better understand the role of telocytes in the architectural organization of the myocardium.EHTs were constructed by seeding neonatal cardiomyocytes in collagen/Matrigel scaffolds followed by culture under persistent static stretch.Telocytes in EHTs were identified by histology,toluidine blue staining,immunofluorescence,and transmission electron microscopy.The results from histology and toluidine blue staining demonstrated widespread putative telocytes with compact toluidine blue-stained nuclei,which were located around cardiomyocytes.Prolongations from the cell bodies showed a characteristic dichotomous branching pattern and formed networks in EHTs.Immunofluorescence revealed positive staining of telocytes for CD34 and vimentin with typical moniliform prolongations.A series of electron microscopy images further showed that typical telocytes embraced the cardiomyocytes with their long prolongations and exhibited a marked appearance of nursing cardiomyocytes during the construction of EHTs.This finding highlights the great importance of telocytes in the architectural organization of EHTs.It also suggests that EHT is an appropriate physical and pathological model system in vitro to study the roles of telocytes during heart development and regeneration.展开更多
Background: Telocytes (TCs) are a novel type of interstitial cells, which have been recently described in a large variety of cavitary and noncavitary organs. TCs have small cell bodies, and remarkably thin, long, a...Background: Telocytes (TCs) are a novel type of interstitial cells, which have been recently described in a large variety of cavitary and noncavitary organs. TCs have small cell bodies, and remarkably thin, long, and moniliform prolongations called telopodes (Tps). Until now, TCs have been found in various loose connective tissues surrounding the arterioles, venules, and capillaries, but as a histological cellular component, whether TCs exist in large arteries remains unexplored. Methods: TCs were identified by transmission electron microscope in the aortic arch of male C57BL/6 mice. Results: TCs in aortic arch had small cell bodies (length: 6.06-13.02 μm: width: 1.05-4.25 μm) with characteristics of specific long (7.74-39.05 μm), thin, and moniliform Tps; TCs distributed in the whole connective tissue layer of tunica adventitia: TCs in the innermost layer of tunica adventitia, located at the juncture between media and adventitia, with their long axes oriented parallel to the outer elastic membrane: and TCs in outer layers oftunica adventitia, were embedded among transverse and longitudinal oriented collagen fibers,forming a highly complex three-dimensional meshwork. Moreover, desmosomes were observed, serving as pathways connecting neighboring Tps. In addition, vesicles shed from the surface of TCs into the extracellular matrix, participating in some biological processes. Conclusions: TCs in aorta arch are a newly recognized complement distinct from other interstitial cells in large arteries, such as fibroblasts. And further biologically functional correlations need to be elucidated.展开更多
Background: This study characterized the cardiac telocyte (TC) population both in vivo and in vitro, and investigated its telomerase activity related to mitosis. Methods: Using transmission electron microscopy and...Background: This study characterized the cardiac telocyte (TC) population both in vivo and in vitro, and investigated its telomerase activity related to mitosis. Methods: Using transmission electron microscopy and a phase contrast microscope, the typical morphological features of cardiac TCs were observed; by targeting the cell surface proteins CD1 17 and CD34, CD 117^+CD34^+ cardiac TCs wcrc sorted via flow cytomctry and validated by immunofluorescence based on the primary cell culture. Then the optimized basal nutrient medium for selected population was examined with the cell counting kit 8. Under this conditioned medium, the process of cell division was captured, and the telomerase activity of CD117^+ CD34^+ cardiac TCs was detected in comparison with bone mesenchymal stem cells (BMSCs), cardiac fibroblasts (CFBs), cardiomyocytes (CMs). Results: Cardiac TCs projected characteristic telopodes with thin segments (podomers) in alternation with dilation (podoms). In addition, 64% of the primary cultured cardiac TCs were composed of CD117^+CD34^+ cardiac TCs: which was verified by immunofluorescence. In a live cell imaging system, CD117^+CD34^+ cardiac TCs were observed to enter into cell division in a short time. followed by an significant invagination forming across the middle of the cell body. Using a real-time quantitative telomeric-repeat amplification assay, the telomerase concentration in CD117^+CD34^+ cardiac TCs was obviously lower than in BMSCs and CFBs, and significantly higher than in CMs. Conclusions: Cardiac TCs represent a unique cell population and CD11 7^+CD34^+ cardiac TCs have relative low telomerase activity that differs from BMSCs, CFBs and CMs and thus they might play an important role in maintaining cardiac homeostasis.展开更多
基金the European Union-NextGenerationEU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘BACKGROUND Multinucleated giant cells(MGCs)in bladder carcinomas are poorly studied.AIM To describe the function,morphogenesis,and origin of mononuclear and MGCs in urothelial carcinoma(UC)of the bladder in Bulgarian and French patients.METHODS Urothelial bladder carcinomas(n=104)from 2016-2020 were analyzed retrospectively using immunohistochemical(IHC)and histochemical stain examination.Giant cells in the bladder stroma were found in 35.6%of cases,more often in highgrades.RESULTS We confirm that MGCs in the mucosa in UC of the bladder were positive for both mesenchymal and myofibroblast markers(vimentin,smooth muscle actin,Desmin,and CD34)and the macrophage marker CD68.Furthermore,IHC studies revealed the following profile of these cells:Positive for p16;negative for epithelial(CK AE1/AE3 and GATA-3),vascular(CD31),neural(PS100 and CKIT),cambial,blastic(CD34-blasts and C-KIT),and immune markers(IG G,immunoglobulin G4,and PD-L1);no proliferative activity,possess no specific immune function,and cannot be used to calculate the Combined Positive Score scale.CONCLUSION In conclusion,the giant stromal cells in non-tumor and tumor bladder can be used as a characteristic and relatively constant,although nonspecific,histological marker for chronic bladder damage,reflecting the chronic irritation or inflammation.Likewise,according to the morphological and IHC of the mono-and multinucleated giant cells in the bladder,they are most likely represent telocytes capable of adapting their morphology to the pathology of the organ.
基金Project supported by the Romanian National Authority for Scientific Research,CNCS-UEFISCDI,PNII(82/2012,194/2014)
文摘Myocardial infarction(MI)is a disorder that lowers the lifespan and quality of life.Reperfusion treatment as early as possible is the most effective solution,with an increased focus on post-MI medication.In the recovery process after MI,telocytes(TCs)appear to play an important role,which develops a large number of questions awaiting answers.Defining possible signaling mechanisms involved in recovery after MI may lead to identification the limits of current therapies,and development of new therapeutic solutions.Key words:telocytes;myocardial infarction;stem
基金supported by the National Natural Science Foundation of China (91339105)the Beijing Natural Science Foundation (7142165)the Science and Technology Commission of Beijing Municipality (z141100000214006)
文摘Telocytes (TCs) are a novel type of interstitial cells that are thought to be involved in tissue regeneration and repair. However, the possible roles of TCs in vascular diseases remain unclear. In this study, we used a rat model of carotid artery balloon injury (CABI) to study the changes and potential roles of vascular TCs after vascular injury. Transmission electron microscopy (TEM) and CD34/vimentin immunolabeling were used to identify and quantify TCs in normal and injured carotid arteries. Quantita- tive immunofluorescence analysis revealed that, compared with the sham group, the number of TCs in the CAB1 group in- creased from 7.2+1.0 to an average of 20.4+1.8 per l-ram2 vascular area. The expression level of miR-24 in TCs was three times higher than in vascular smooth muscle cells (VSMCs). The percentage of VSMCs in S phase and G2/M phase increased by approximately 5% when VSMCs were incubated with the supematant of TCs. The antagomir of miR-24 in TCs reduced the ratio of VSMCs in S ohase and G2/M phase. This study illuminates the function of TCs in the proliferation of VSMCs.
基金supported by the National High Technology Research and Development Program of China(2012AA020506)Key Program of National Natural Science Foundation of China(31030032)+1 种基金National Natural Science Funds for Distinguished Young Scholar(31025013)the National Natural Science Foundation of China(31100697)
文摘Interstitial Cajal-like cells are a distinct type of interstitial cell with a wide distribution in mammalian organs and tissues,and have been given the name"telocytes".Recent studies have demonstrated the potential roles of telocytes in heart development,renewal,and repair.However,further research on the functions of telocytes is limited by the complicated in vivo environment.This study was designed to construct engineered heart tissue(EHT)as a three-dimensional model in vitro to better understand the role of telocytes in the architectural organization of the myocardium.EHTs were constructed by seeding neonatal cardiomyocytes in collagen/Matrigel scaffolds followed by culture under persistent static stretch.Telocytes in EHTs were identified by histology,toluidine blue staining,immunofluorescence,and transmission electron microscopy.The results from histology and toluidine blue staining demonstrated widespread putative telocytes with compact toluidine blue-stained nuclei,which were located around cardiomyocytes.Prolongations from the cell bodies showed a characteristic dichotomous branching pattern and formed networks in EHTs.Immunofluorescence revealed positive staining of telocytes for CD34 and vimentin with typical moniliform prolongations.A series of electron microscopy images further showed that typical telocytes embraced the cardiomyocytes with their long prolongations and exhibited a marked appearance of nursing cardiomyocytes during the construction of EHTs.This finding highlights the great importance of telocytes in the architectural organization of EHTs.It also suggests that EHT is an appropriate physical and pathological model system in vitro to study the roles of telocytes during heart development and regeneration.
基金This study was supported by a grant from the Young Scientists Fund of the National Natural Science Foundation of China
文摘Background: Telocytes (TCs) are a novel type of interstitial cells, which have been recently described in a large variety of cavitary and noncavitary organs. TCs have small cell bodies, and remarkably thin, long, and moniliform prolongations called telopodes (Tps). Until now, TCs have been found in various loose connective tissues surrounding the arterioles, venules, and capillaries, but as a histological cellular component, whether TCs exist in large arteries remains unexplored. Methods: TCs were identified by transmission electron microscope in the aortic arch of male C57BL/6 mice. Results: TCs in aortic arch had small cell bodies (length: 6.06-13.02 μm: width: 1.05-4.25 μm) with characteristics of specific long (7.74-39.05 μm), thin, and moniliform Tps; TCs distributed in the whole connective tissue layer of tunica adventitia: TCs in the innermost layer of tunica adventitia, located at the juncture between media and adventitia, with their long axes oriented parallel to the outer elastic membrane: and TCs in outer layers oftunica adventitia, were embedded among transverse and longitudinal oriented collagen fibers,forming a highly complex three-dimensional meshwork. Moreover, desmosomes were observed, serving as pathways connecting neighboring Tps. In addition, vesicles shed from the surface of TCs into the extracellular matrix, participating in some biological processes. Conclusions: TCs in aorta arch are a newly recognized complement distinct from other interstitial cells in large arteries, such as fibroblasts. And further biologically functional correlations need to be elucidated.
基金Source of Support: This study was supported by a grant from the Young Scientists Fund of the National Natural Science Foundation of China (No, 81300232). Conflict of Interest: None dec ared.
文摘Background: This study characterized the cardiac telocyte (TC) population both in vivo and in vitro, and investigated its telomerase activity related to mitosis. Methods: Using transmission electron microscopy and a phase contrast microscope, the typical morphological features of cardiac TCs were observed; by targeting the cell surface proteins CD1 17 and CD34, CD 117^+CD34^+ cardiac TCs wcrc sorted via flow cytomctry and validated by immunofluorescence based on the primary cell culture. Then the optimized basal nutrient medium for selected population was examined with the cell counting kit 8. Under this conditioned medium, the process of cell division was captured, and the telomerase activity of CD117^+ CD34^+ cardiac TCs was detected in comparison with bone mesenchymal stem cells (BMSCs), cardiac fibroblasts (CFBs), cardiomyocytes (CMs). Results: Cardiac TCs projected characteristic telopodes with thin segments (podomers) in alternation with dilation (podoms). In addition, 64% of the primary cultured cardiac TCs were composed of CD117^+CD34^+ cardiac TCs: which was verified by immunofluorescence. In a live cell imaging system, CD117^+CD34^+ cardiac TCs were observed to enter into cell division in a short time. followed by an significant invagination forming across the middle of the cell body. Using a real-time quantitative telomeric-repeat amplification assay, the telomerase concentration in CD117^+CD34^+ cardiac TCs was obviously lower than in BMSCs and CFBs, and significantly higher than in CMs. Conclusions: Cardiac TCs represent a unique cell population and CD11 7^+CD34^+ cardiac TCs have relative low telomerase activity that differs from BMSCs, CFBs and CMs and thus they might play an important role in maintaining cardiac homeostasis.