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Nicole Gui Zhen Tee Sze Yun Lim Manasi Nandihalli Chrishan J.A. Ramachandra Ashish Mehta Winston Shim 《Journal of cellular and molecular medicine》2016,20(2):323-332
We investigate the effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)‐derived progenitors and cardiomyocytes into acutely infarcted myocardium in severe combined immune deficiency mice. A total of 2 × 105 progenitors, cardiomyocytes or cell‐free saline were injected into peri‐infarcted anterior free wall. Sham‐operated animals received no injection. Myocardial function was assessed at 2‐week and 4‐week post‐infarction by using echocardiography and pressure‐volume catheterization. Early myocardial remodelling was observed at 2‐week with echocardiography derived stroke volume (SV) in saline (20.45 ± 7.36 μl, P < 0.05) and cardiomyocyte (19.52 ± 3.97 μl, P < 0.05) groups, but not in progenitor group (25.65 ± 3.61 μl), significantly deteriorated as compared to sham control group (28.41 ± 4.41 μl). Consistently, pressure – volume haemodynamic measurements showed worsening chamber dilation in saline (EDV: 23.24 ± 5.01 μl, P < 0.05; ESV: 17.08 ± 5.82 μl, P < 0.05) and cardiomyocyte (EDV: 26.45 ± 5.69 μl, P < 0.05; ESV: 18.03 ± 6.58 μl, P < 0.05) groups by 4‐week post‐infarction as compared to control (EDV: 15.26 ± 2.96 μl; ESV: 8.41 ± 2.94 μl). In contrast, cardiac progenitors (EDV: 20.09 ± 7.76 μl; ESV: 13.98 ± 6.74 μl) persistently protected chamber geometry against negative cardiac remodelling. Similarly, as compared to sham control (54.64 ± 11.37%), LV ejection fraction was preserved in progenitor group from 2‐(38.68 ± 7.34%) to 4‐week (39.56 ± 13.26%) while cardiomyocyte (36.52 ± 11.39%, P < 0.05) and saline (35.34 ± 11.86%, P < 0.05) groups deteriorated early at 2‐week. Improvements of myocardial function in the progenitor group corresponded to increased vascularization (16.12 ± 1.49/mm2 to 25.48 ± 2.08/mm2 myocardial tissue, P < 0.05) and coincided with augmented networking of cardiac telocytes in the interstitial space of infarcted zone. 相似文献
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Baoyin Zhao Shang Chen Juanjuan Liu Ziqiang Yuan Xufeng Qi Junwen Qin Xin Zheng Xiaotao Shen Yanhong Yu Thomas J. Qnin John Yeuk‐Hon Chan Dongqing Cai 《Journal of cellular and molecular medicine》2013,17(1):123-133
Recently, cardiac telocytes were found in the myocardium. However, the functional role of cardiac telocytes and possible changes in the cardiac telocyte population during myocardial infarction in the myocardium are not known. In this study, the role of the recently identified cardiac telocytes in myocardial infarction (MI) was investigated. Cardiac telocytes were distributed longitudinally and within the cross network of the myocardium, which was impaired during MI. Cardiac telocytes in the infarction zone were undetectable from approximately 4 days to 4 weeks after an experimental coronary occlusion was used to induce MI. Although cardiac telocytes in the non‐ischaemic area of the ischaemic heart experienced cell death, the cell density increased approximately 2 weeks after experimental coronary occlusion. The cell density was then maintained at a level similar to that observed 1–4 days after left anterior descending coronary artery (LAD)‐ligation, but was still lower than normal after 2 weeks. We also found that simultaneous transplantation of cardiac telocytes in the infarcted and border zones of the heart decreased the infarction size and improved myocardial function. These data indicate that cardiac telocytes, their secreted factors and microvesicles, and the microenvironment may be structurally and functionally important for maintenance of the physiological integrity of the myocardium. Rebuilding the cardiac telocyte network in the infarcted zone following MI may be beneficial for functional regeneration of the infarcted myocardium. 相似文献
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Keisuke Nakajima Taeko Nakajima Minoru Takase Yoshio Yaoita 《Development, growth & differentiation》2012,54(9):777-784
To generate albino lines of Xenopus tropicalis, we injected fertilized eggs with mRNAs encoding zinc‐finger nucleases (ZFNs) targeting the tyrosinase coding region. Surprisingly, vitiligo was observed on the skin of F0 frogs that had been injected with ZFN mRNAs, indicating that both tyrosinase genes in the genome were disrupted in all melanocytes within the vitiligo patches. Mutation analysis using genomic DNA from the skin revealed that two mosaic F0 frogs underwent spatially complex tyrosinase gene mutations. The data implies that the ZFN‐induced tyrosinase gene ablations occurred randomly over space and time throughout the entire body, possibly until the young tadpole stage, and that melanocyte precursors lacking functional tyrosinase proliferated and formed vitiligo patches. Several albino X. tropicalis, which are compound heterozygotes for biallelic tyrosinase mutations, were obtained by mating the mosaic F0 frogs. To our knowledge, this is the first report of the albino vertebrates generated by the targeted gene knockout. 相似文献
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Maria‐Simonetta Faussone‐Pellegrini D. Bani 《Journal of cellular and molecular medicine》2010,14(5):1061-1063
Evidence has been given that the adult heart contains a specific population of stromal cells lying in close spatial relationship with cardiomyocytes and with cardiac stem cells in sub‐epicardial cardiogenic niches. Recently termed ‘telocytes’ because of their long cytoplasmic processes embracing the parenchymal cells, these cells have been postulated to be involved in heart morphogenesis. In our opinion, investigating the occurrence and morphology of telocytes during heart histogenesis may shed further light on this issue. Our findings show that typical telocytes are present in the mouse heart by early embryonic to adult life. These cells closely embrace the growing cardiomyocytes with their long, slender cytoplasmic processes. Hence, in the developing myocardium, telocytes may play nursing and guiding roles for myocardial precursors to form the correct three‐dimensional tissue architectural pattern, as previously suggested. 相似文献
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A highly heterogeneous population of stem and progenitor cells has been described by light immunohistochemistry in the mammalian adult heart, but the ultrastructural identity of cardiac stem cells remains unknown. Using electron microscopy, we demonstrate the presence of cells with stem features in the adult mouse heart. These putative cardiac stem cells are small (6–10 μm), round cells, with an irregular shaped nucleus, large nucleolus, few endoplasmic reticulum cisternae and mitochondria, but numerous ribosomes. Stem cells located in the epicardial stem cell niche undergo mitosis and apoptosis. Cells with intermediate features between stem cells and cardiomyocyte progenitors have also been seen. Moreover, electron microscopy showed that cardiomyocyte progenitors were added to the peripheral working cardiomyocytes. Telocytes make a supportive interstitial network for stem cells and progenitors in the stem cell niche. This study enhances the hypothesis of a unique type of cardiac stem cell and progenitors in different stages of differentiation. In our opinion, stem cells, cardiomyocyte progenitors and telocytes sustain a continuous cardiac renewal process in the adult mammalian heart. 相似文献
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Yoko Wakabayashi Yuko Naora Takekazu Kunieda Taro Fukazawa Takeo Kubo 《Development, growth & differentiation》2016,58(9):688-701
Regeneration of lost organs involves complex processes, including host defense from infection and rebuilding of lost tissues. We previously reported that Xenopus neuronal pentraxin I (xNP1) is expressed preferentially in regenerating Xenopus laevis tadpole tails. To evaluate xNP1 function in tail regeneration, and also in tail development, we analyzed xNP1 expression in tailbud embryos and regenerating/healing tails following tail amputation in the ‘regeneration’ period, as well as in the ‘refractory’ period, when tadpoles lose their tail regenerative ability. Within 10 h after tail amputation, xNP1 was induced at the amputation site regardless of the tail regenerative ability, suggesting that xNP1 functions in acute phase responses. xNP1 was widely expressed in regenerating tails, but not in the tail buds of tailbud embryos, suggesting its possible role in the immune response/healing after an injury. xNP1 expression was also observed in neural tissues/primordia in tailbud embryos and in the spinal cord in regenerating/healing tails in both periods, implying its possible roles in neural development or function. Moreover, during the first 48 h after amputation, xNP1 expression was sustained at the spinal cord of tails in the ‘regeneration’ period tadpoles, but not in the ‘refractory’ period tadpoles, suggesting that xNP1 expression at the spinal cord correlates with regeneration. Our findings suggest that xNP1 is involved in both acute phase responses and neural development/functions, which is unique compared to mammalian pentraxins whose family members are specialized in either acute phase responses or neural functions. 相似文献
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Bani D Formigli L Gherghiceanu M Faussone-Pellegrini MS 《Journal of cellular and molecular medicine》2010,14(10):2531-2538
Recent evidence indicates that the adult heart contains sub-epicardial cardiogenic niches where cardiac stem cells and stromal supporting cells reside together. Such stromal cells include a special population, previously identified as interstitial Cajal-like cells and recently termed telocytes because of their long, slender processes (telopodes) embracing the myocardial precursors. Specific stromal cells, presumptively originated from the epicardium, have been postulated to populate the developing heart where they are thought to play a role in its morphogenesis. This study is designed to investigate the occurrence of telocytes in the developing heart and provide clues to better understand their role as supporting cells involved in the architectural organization of the myocardium during heart development. Our results showed that stromal cells with the immunophenotypical (vimentin, CD34) and ultrastructural features of telocytes were present in the mouse heart since early embryonic to adult life, as well as in primary cultures of neonatal mouse cardiac cells. These cells formed an extended network of telopodes which closely embraced the growing cardiomyocytes and appeared to contribute to the aggregation of cardiomyocyte clusters in vitro. In conclusion, the present findings strongly suggest that, during heart development, stromal cells identifiable as telocytes could play a nursing and guiding role for myocardial precursors to form the correct three-dimensional tissue pattern and contribute to compaction of the embryonic myocardial trabeculae. It is tempting to speculate that telocytes could be a novel, possible target for therapeutic strategies aimed at potentiating cardiac repair and regeneration after ischemic injury. 相似文献
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Xiaofeng Qin Shufang Gao Yadong Yang Leilei Wu Liming Wang 《Journal of cellular physiology》2019,234(12):22103-22115
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Laurentiu M. Popescu Shengshou Hu Mihaela Gherghiceanu 《Journal of cellular and molecular medicine》2015,19(1):31-45
Tradition considers that mammalian heart consists of about 70% non‐myocytes (interstitial cells) and 30% cardiomyocytes (CMs). Anyway, the presence of telocytes (TCs) has been overlooked, since they were described in 2010 (visit www.telocytes.com ). Also, the number of cardiac stem cells (CSCs) has not accurately estimated in humans during ageing. We used electron microscopy to identify and estimate the number of cells in human atrial myocardium (appendages). Three age‐related groups were studied: newborns (17 days–1 year), children (6–17 years) and adults (34–60 years). Morphometry was performed on low‐magnification electron microscope images using computer‐assisted technology. We found that interstitial area gradually increases with age from 31.3 ± 4.9% in newborns to 41 ± 5.2% in adults. Also, the number of blood capillaries (per mm2) increased with several hundreds in children and adults versus newborns. CMs are the most numerous cells, representing 76% in newborns, 88% in children and 86% in adults. Images of CMs mitoses were seen in the 17‐day newborns. Interestingly, no lipofuscin granules were found in CMs of human newborns and children. The percentage of cells that occupy interstitium were (depending on age): endothelial cells 52–62%; vascular smooth muscle cells and pericytes 22–28%, Schwann cells with nerve endings 6–7%, fibroblasts 3–10%, macrophages 1–8%, TCs about 1% and stem cells less than 1%. We cannot confirm the popular belief that cardiac fibroblasts are the most prevalent cell type in the heart and account for about 20% of myocardial volume. Numerically, TCs represent a small fraction of human cardiac interstitial cells, but because of their extensive telopodes, they achieve a 3D network that, for instance, supports CSCs. The myocardial (very) low capability to regenerate may be explained by the number of CSCs, which decreases fivefold by age (from 0.5% to 0.1% in newborns versus adults). 相似文献
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Baoyin Zhao Zhaofu Liao Shang Chen Ziqiang Yuan Chen Yilin Kenneth K.H. Lee Xufeng Qi Xiaotao Shen Xin Zheng Thomas Quinn Dongqing Cai 《Journal of cellular and molecular medicine》2014,18(5):780-789
The midterm effects of cardiac telocytes (CTs) transplantation on myocardial infarction (MI) and the cellular mechanisms involved in the beneficial effects of CTs transplantation are not understood. In the present study, we have revealed that transplantation of CTs was able to significantly decrease the infarct size and improved cardiac function 14 weeks after MI. It has established that CT transplantation exerted a protective effect on the myocardium and this was maintained for at least 14 weeks. The cellular mechanism behind this beneficial effect on MI was partially attributed to increased cardiac angiogenesis, improved reconstruction of the CT network and decreased myocardial fibrosis. These combined effects decreased the infarct size, improved the reconstruction of the LV and enhanced myocardial function in MI. Our findings suggest that CTs could be considered as a potential cell source for therapeutic use to improve cardiac repair and function following MI, used either alone or in tandem with stem cells. 相似文献
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Xiaoke Chen Yonghua Zheng Catalin G. Manole Xiangdong Wang Qun Wang 《Journal of cellular and molecular medicine》2013,17(11):1506-1512
Telocytes (TCs), a new type of interstitial cells, were identified in many different organs and tissues of mammalians and humans. In this study, we show the presence, in human oesophagus, of cells having the typical features of TCs in lamina propria of the mucosa, as well as in muscular layers. We used transmission electron microscopy (TEM), immunohistochemistry (IHC) and primary cell culture. Human oesophageal TCs present a small cell body with 2–3 very long Telopodes (Tps). Tps consist of an alternation of thin segments (podomers) and thick segments (podoms) and have a labyrinthine spatial arrangement. Tps establish close contacts (‘stromal synapses’) with other neighbouring cells (e.g. lymphocytes, macrophages). The ELISA testing of the supernatant of primary culture of TCs indicated that the concentrations of VEGF and EGF increased progressively. In conclusion, our study shows the existence of typical TCs at the level of oesophagus (mucosa, submucosa and muscular layer) and suggests their possible role in tissue repair. 相似文献
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Myocardium is composed of two main cell populations: cardiomyocytes (CMs) and interstitial cells (e.g. fibroblasts, immunoreactive cells, capillaries). However, very recently we have showed that a novel type of interstitial cell called telocytes (TCs) does exist in epi-, myo- and endocardium. They have very long and thin telopodes (Tp) formed by alternating podomeres and podoms. Heterocellular communication between TCs and CMs it is supposed to occur by shed vesicles and close apposition. If TCs have to play a role in cardiac physiology it is expected to develop direct and unambiguous contacts with CMs. Because a clear membrane-to-membrane junction has not been reported by electron microscopy we have investigated the heterocellular communication in the mouse heart by electron tomography. This advanced technique showed that small dense structures (10-15 nm nanocontacts) directly connect TCs with CMs. More complex and atypical junctions could be observed between TCs and CMs at the level of intercalated discs. This study proves that TCs and CMs are directly connected and might represent a 'functional unit'. 相似文献
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Species‐specific detection of Candida tropicalis using evolutionary conserved intein DNA sequences
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S.K. Rajasekharan A.K. Ray S. Ramesh S. Kannappan Mohanvel 《Letters in applied microbiology》2018,66(5):378-383
Inteins (internal proteins) are self‐splicing transportable genetic elements present in conserved regions of housekeeping genes. The study highlights the importance of intein as a potential diagnostic marker for species‐specific identification of Candida tropicalis, a rapidly emerging opportunistic human pathogen. Initial steps of primer validation, sequence alignment, phylogenetic tree analysis, gel electrophoresis and real‐time polymerase chain reaction (PCR) assays were performed to confirm the specificity of the designed primers. The primers were selective for C. tropicalis with 100% inclusivity and showed no cross‐species or cross‐genera matches. The established technique is a prototype for developing multifaceted PCR assays and for point‐of‐care testing in near future.
Significance and Impact of the Study
Development of molecular markers for specific detection of microbial pathogens using real‐time polymerase chain reaction (PCR) is an appealing and challenging technique. A real‐time PCR is an emerging technology frequently used to detect the aetiologic agents. In recent times, designing species‐specific primers for pathogen detection is gaining momentum. The method offers rapid, accurate and cost‐effective strategy to identify the target, thus providing sufficient time to instigate appropriate chemotherapy. The study highlights the use of intein DNA sequence as molecular markers for species‐specific identification of Candida tropicalis. The study also offers a prototype model for developing multifaceted PCR assays using intein DNA sequences, and provides a developmental starting point for point‐of‐care testing in near future. 相似文献18.
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Antony J. Durston 《Genesis (New York, N.Y. : 2000)》2019,57(7-8)
This article is concerned with the roles of retinoids and other known anterior–posterior morphogens in setting up the embryonic vertebrate anterior–posterior axis. The discussion is restricted to the very earliest events in setting up the anterior–posterior axis (from blastula to tailbud stages in Xenopus embryos). In these earliest developmental stages, morphogen concentration gradients are not relevant for setting up this axis. It emerges that at these stages, the core patterning mechanism is timing: BMP‐anti BMP mediated time space translation that regulates Hox temporal and spatial collinearities and Hox‐Hox auto‐ and cross‐ regulation. The known anterior–posterior morphogens and signaling pathways––retinoids, FGF's, Cdx, Wnts, Gdf11 and others––interact with this core mechanism at and after space–time defined “decision points,” leading to the separation of distinct axial domains. There are also other roles for signaling pathways. Besides the Hox regulated hindbrain/trunk part of the axis, there is a rostral part (including the anterior part of the head and the extreme anterior domain [EAD]) that appears to be regulated by additional mechanisms. Key aspects of anterior–posterior axial patterning, including: the nature of different phases in early patterning and in the whole process; the specificities of Hox action and of intercellular signaling; and the mechanisms of Hox temporal and spatial collinearities, are discussed in relation to the facts and hypotheses proposed above. 相似文献