Academic literature on the topic 'Fibroblastos NHDF'
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Journal articles on the topic "Fibroblastos NHDF"
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Chee, Ana, Peng Shi, Thomas Cha, et al. "Cell Therapy with Human Dermal Fibroblasts Enhances Intervertebral Disk Repair and Decreases Inflammation in the Rabbit Model." Global Spine Journal 6, no. 8 (2016): 771–79. http://dx.doi.org/10.1055/s-0036-1582391.
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Study Design Pilot study using the rabbit model. Objective Low back pain is often associated with disk degeneration. Cell therapy for degenerating disks may promote tissue regeneration and repair. Human dermal fibroblasts, obtained from the patient's skin tissue or donated tissue, may be a promising cell therapy option for degenerating disks. The objective of these studies is to determine the effects of intradiscal transplantation of neonatal human dermal fibroblasts (nHDFs) on intervertebral disk (IVD) degeneration by measuring disk height, magnetic resonance imaging (MRI) signal intensity, gene expression, and collagen immunostaining. Methods New Zealand white rabbits ( n = 16) received an annular puncture to induce disk degeneration and were treated with nHDFs or saline 4 weeks later. At 2 and 8 weeks post-treatment, X-ray and MRI images were obtained. IVDs were isolated and examined for changes in collagen staining and gene expression. Results In the nHDF-treated group, there was a 10% increase in the disk height index after 8 weeks of treatment ( p ≤ 0.05), and there was no significant difference in the saline-treated group. When compared with the saline-treated disks, disks treated with nHDFs showed reduced expression of inflammatory markers, a higher ratio of collagen type II over collagen type I gene expression, and more intense immunohistochemical staining for both collagen types I and II. Conclusions Human dermal fibroblast introduction into the disk reduced inflammation and promoted tissue rich in both type I and type II collagens. The results of this study suggest that nHDFs would be a feasible cell therapy option for disk degeneration.
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Kamiya, Yuki, Mao Odama, Aki Mizuguti, Shigeru Murakami, and Takashi Ito. "Puerarin blocks the aging phenotype in human dermal fibroblasts." PLOS ONE 16, no. 4 (2021): e0249367. http://dx.doi.org/10.1371/journal.pone.0249367.
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Dermal fibroblast aging contributes to aging-associated functional defects in the skin since dermal fibroblasts maintain skin homeostasis by interacting with the epidermis and extracellular matrix. Here, we found that puerarin, an isoflavone present in Pueraria lobata (Kudzu), can prevent the development of the aging-phenotype in human dermal fibroblasts. Normal human dermal fibroblasts (NHDFs) were subcultivated and high-passage cells were selected as senescent cells, whereas low-passage cells were selected as a young cell control. Puerarin treatment increased cell proliferation and decreased the proportion of senescence-associated beta-galactosidase-positive cells in a high-passage culture of NHDFs. Moreover, puerarin treatment reduced the number of smooth muscle actin (SMA)-positive myofibroblasts and the expression of a reticular fibroblast marker, calponin 1 (CNN1), which were induced in high-passage NHDFs. Fulvestrant, an estrogen receptor antagonist, blocked the puerarin-mediated downregulation of SMA and CNN1. Our results suggest that puerarin may be a useful functional food that alleviates aging-related functional defects in dermal fibroblasts.
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Lim, Seong-Ryeong, Do-Wan Kim, Junghee Sung, Tae Hoon Kim, Chang-Hyung Choi, and Sei-Jung Lee. "Astaxanthin Inhibits Autophagic Cell Death Induced by Bisphenol A in Human Dermal Fibroblasts." Antioxidants 10, no. 8 (2021): 1273. http://dx.doi.org/10.3390/antiox10081273.
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Astaxanthin, a natural antioxidant carotenoid, is a nutrient with diverse health benefits, given that it decreases the risk of oxidative stress-related diseases. In the present study, we investigate the functional role of astaxanthin during autophagic cell death induced by the estrogenic endocrine-disrupting chemical bisphenol A (BPA) in normal human dermal fibroblasts (NHDF). BPA significantly induced apoptotic cell death and autophagy in NHDF. Autophagic cell death evoked by BPA was significantly restored upon a treatment with astaxanthin (10 μM) via the inhibition of intracellular reactive oxygen species (ROS) production. Astaxanthin inhibited the phosphorylation of extracellular signal-regulated kinases (ERK) stimulated by ROS production, but it did not influence the activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in BPA-treated NHDF. Astaxanthin abrogated the ERK-mediated activation of nuclear factor-kappa B (NF-κB), which is responsible for the mRNA expression of LC3-II, Beclin-1, Atg12, and Atg14 during apoptotic cell death induced by BPA. These results indicate that astaxanthin is a pharmacological and nutritional agent that blocks the skin fibroblastic autophagic cell death induced by BPA in human dermal fibroblasts.
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Park, Su-Ji, Do-Wan Kim, Seong-Ryeong Lim та ін. "Kaempferol Blocks the Skin Fibroblastic Interleukin 1β Expression and Cytotoxicity Induced by 12-O-tetradecanoylphorbol-13-acetate by Suppressing c-Jun N-terminal Kinase". Nutrients 13, № 9 (2021): 3079. http://dx.doi.org/10.3390/nu13093079.
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Kaempferol, a bioflavonoid present in fruits and vegetables, has a variety of antioxidant and anti-inflammatory capacities, but the functional role of kaempferol in oxidative skin dermal damage has yet to be well studied. In this study, we examine the role of kaempferol during the inflammation and cell death caused by 12-O-tetradecanoylphorbol-13-acetate (TPA) in normal human dermal fibroblasts (NHDF). TPA (5 μM) significantly induced cytotoxicity of NHDF, where a robust increase in the interleukin (IL)-1β mRNA among the various pro-inflammatory cytokines. The skin fibroblastic cytotoxicity and IL-1β expression induced by TPA were significantly ameliorated by a treatment with 100 nM of kaempferol. Kaempferol blocked the production of the intracellular reactive oxygen species (ROS) responsible for the phosphorylation of c-Jun N-terminal kinase (JNK) induced by TPA. Interestingly, we found that kaempferol inhibited the phosphorylation of nuclear factor-kappa B (NF-κB) and the inhibitor NF-κB (IκBα), which are necessary for the expression of cleaved caspase-3 and the IL-1β secretion in TPA-treated NHDF. These results suggest that kaempferol is a functional agent that blocks the signaling cascade of the skin fibroblastic inflammatory response and cytotoxicity triggered by TPA.
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Nie, W., and A. M. Deters. "Tamarind Seed Xyloglucans Promote Proliferation and Migration of Human Skin Cells through Internalization via Stimulation of Proproliferative Signal Transduction Pathways." Dermatology Research and Practice 2013 (2013): 1–14. http://dx.doi.org/10.1155/2013/359756.
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Xyloglucans (XGs) ofTamarindus indicaL. Fabaceae are used as drug vehicles or as ingredients of cosmetics. Two xyloglucans were extracted fromT. indicaseed with cold water (TSw) and copper complex precipitation (TSc). Both were analyzed in regard to composition and influence on cell viability, proliferation, cell cycle progression, migration, MAPK phosphorylation, and gene expression of human skin keratinocytes (NHEK and HaCaT) and fibroblasts (NHDF)in vitro. TSw and TSc differed in molecular weight, rhamnose content, and ratios of xylose, arabinose, galactose, and glucose. Both XGs improved keratinocytes and fibroblast proliferation, promoted the cell cycle, and stimulated migration and intracellular enzyme activity of NHDF after endosomal uptake. Only TSw significantly enhanced HaCaT migration and extracellular enzyme activity of NHDF and HaCaT. TSw and TSc predominantly enhanced the phosphorylation of molecules that referred to Erk signaling in NHEK. In NHDF parts of the integrin signaling and SAPK/JNK pathway were affected. Independent of cell type TSw marginally regulated the expression of genes, which referred to membrane proteins, cytoskeleton, cytokine signaling, and ECM as well as to processes of metabolism and transcription. Results show thatT. indicaxyloglucans promote skin regeneration by a direct influence on cell proliferation and migration.
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Kougias, Panagiotis, Duo Wei, Peter J. Rice та ін. "Normal Human Fibroblasts Express Pattern Recognition Receptors for Fungal (1→3)-β-d-Glucans". Infection and Immunity 69, № 6 (2001): 3933–38. http://dx.doi.org/10.1128/iai.69.6.3933-3938.2001.
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ABSTRACT Fungal cell wall glucans nonspecifically stimulate various aspects of innate immunity. Glucans are thought to mediate their effects via interaction with membrane receptors on macrophages, neutrophils, and NK cells. There have been no reports of glucan receptors on nonimmune cells. We investigated the binding of a water-soluble glucan in primary cultures of normal human dermal fibroblasts (NHDF). Membranes from NHDF exhibited saturable binding with an apparent dissociation constant (K D ) of 8.9 ± 1.9 μg of protein per ml and a maximum binding of 100 ± 8 resonance units. Competition studies demonstrated the presence of at least two glucan binding sites on NHDF. Glucan phosphate competed for all binding sites, with a K D of 5.6 μM (95% confidence interval [CI], 3.0 to 11 μM), while laminarin competed for 69% ± 6% of binding sites, with a K D of 3.7 μM (95% CI, 1.9 to 7.3 μM). Glucan (1 μg/ml) stimulated fibroblast NF-κB nuclear binding activity and interleukin 6 (IL-6) gene expression in a time-dependent manner. NF-κB was activated at 4, 8, and 12 h, while IL-6 mRNA levels were increased by 48% at 8 h. This is the first report of pattern recognition receptors for glucan on human fibroblasts and the first demonstration of glucan binding sites on cells other than leukocytes. It also provides the first evidence that glucans can directly modulate the functional activity of NHDF. These results provide new insights into the mechanisms by which the host recognizes and responds to fungal (1→3)-β-d-glucans and suggests that the response to glucans may not be confined to cells of the immune system.
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Ly, Thanh-Diep, Christopher Lindenkamp, Eva Kara, et al. "The Impact of Inflammatory Stimuli on Xylosyltransferase-I Regulation in Primary Human Dermal Fibroblasts." Biomedicines 10, no. 6 (2022): 1451. http://dx.doi.org/10.3390/biomedicines10061451.
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Inflammation plays a vital role in regulating fibrotic processes. Beside their classical role in extracellular matrix synthesis and remodeling, fibroblasts act as immune sentinel cells participating in regulating immune responses. The human xylosyltransferase-I (XT-I) catalyzes the initial step in proteoglycan biosynthesis and was shown to be upregulated in normal human dermal fibroblasts (NHDF) under fibrotic conditions. Regarding inflammation, the regulation of XT-I remains elusive. This study aims to investigate the effect of lipopolysaccharide (LPS), a prototypical pathogen-associated molecular pattern, and the damage-associated molecular pattern adenosine triphosphate (ATP) on the expression of XYLT1 and XT-I activity of NHDF. We used an in vitro cell culture model and mimicked the inflammatory tissue environment by exogenous LPS and ATP supplementation. Combining gene expression analyses, enzyme activity assays, and targeted gene silencing, we found a hitherto unknown mechanism involving the inflammasome pathway components cathepsin B (CTSB) and caspase-1 in XT-I regulation. The suppressive role of CTSB on the expression of XYLT1 was further validated by the quantification of CTSB expression in fibroblasts from patients with the inflammation-associated disease Pseudoxanthoma elasticum. Altogether, this study further improves the mechanistic understanding of inflammatory XT-I regulation and provides evidence for fibroblast-targeted therapies in inflammatory diseases.
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Wcisło-Dziadecka, Dominika, Beniamin Grabarek, Nikola Zmarzły, et al. "Influence of Adalimumab on the Expression Profile of Genes Associated with the Histaminergic System in the Skin Fibroblasts In Vitro." BioMed Research International 2018 (2018): 1–11. http://dx.doi.org/10.1155/2018/1582173.
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Objective. The aim of this study was to evaluate the influence of adalimumab on expression profile of genes associated with the histaminergic system in Normal Human Dermal Fibroblast (NHDF) cells stimulated with 8.00 μg/ml of adalimumab and the identification of miRNAs regulating these genes’ expression. Methods. NHDFs were cultured with or without the presence of adalimumab for 2, 8, and 24 hours. The expression profile of genes and miRNA were determined with the use of microarray technology. Results. Among 22283 ID mRNA, 65 are associated with the histaminergic system. It can be observed that 15 mRNAs differentiate NHDFs cultures with adalimumab form control. The analysis of miRNAs showed that, among 1105 ID miRNA, 20 miRNAs are differentiating in cells treated with adalimumab for 2 hours, 9 miRNA after 8 hours, and only 3 miRNAs after 24 hours. Conclusion. It was also determined that miRNAs play certain role in the regulation of the expression of genes associated with the histaminergic system. The results of this study confirmed the possibility of using both genes associated with this system as well as miRNAs regulating their expression, as complementary molecular markers of sensitivity to the adalimumab treatment.
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Arvia, Rosaria, Francesca Margheri, Maria A. Stincarelli, et al. "Parvovirus B19 activates in vitro normal human dermal fibroblasts: a possible implication in skin fibrosis and systemic sclerosis." Rheumatology 59, no. 11 (2020): 3526–32. http://dx.doi.org/10.1093/rheumatology/keaa230.
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Abstract Objective Fibrosis is the most characteristic pathological hallmark of SSc, a connective tissue disease characterized by vascular and immunological abnormalities, inflammation and enhanced extracellular matrix production, leading to progressive fibrosis of skin and internal organs. We previously demonstrated that parvovirus B19 (B19V) can infect normal human dermal fibroblasts (NHDFs) and that B19V persists in SSc fibroblasts. In this study, we investigated whether parvovirus B19V is able to activate in vitro NHDFs and to induce in these cells some phenotypic features similar to that observed in the SSc fibroblasts. Methods We preliminarily analysed the time course of B19V infection in cultured NHDFs, then we investigated the ability of B19V to induce cell migration, invasive phenotype and mRNA expression of some profibrotic and/or proinflammatory genes. Results We confirmed our previous findings that B19V infects NHDFs, but the infection is not productive. After incubation with B19V, NHDFs showed a significant increase of both migration and invasiveness, along with mRNA expression of different profibrotic genes (α-SMA, EDN-1, IL-6, TGF-β1 receptors 1 and 2, Col1α2), some genes associated with inflammasome platform (AIM2, IFI16, IL-1β, CASP-1) and genes for metalloprotease (MMP 2, 9 and 12). Conclusion These data suggest that B19V can activate dermal fibroblasts and may have a role in the pathogenesis of fibrosis. B19V-induced fibroblast migration and invasiveness could be due to the B19V-associated MMP9 overexpression and activation. Moreover, the up-regulation of MMP12, typical of SSc, could link the B19V infection of fibroblasts to the anti-angiogenic process.
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Koukorava, Chrysa, Kelly Ward, Katie Ahmed, et al. "Mesothelial Cells Exhibit Characteristics of Perivascular Cells in an In Vitro Angiogenesis Assay." Cells 12, no. 20 (2023): 2436. http://dx.doi.org/10.3390/cells12202436.
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Mesothelial cells have been shown to have remarkable plasticity towards mesenchymal cell types during development and in disease situations. Here, we have characterized the potential of mesothelial cells to undergo changes toward perivascular cells using an in vitro angiogenesis assay. We demonstrate that GFP-labeled mesothelial cells (GFP-MCs) aligned closely and specifically with endothelial networks formed when human dermal microvascular endothelial cells (HDMECs) were cultured in the presence of VEGF-A165 on normal human dermal fibroblasts (NHDFs) for a 7-day period. The co-culture with GFP-MCs had a positive effect on branch point formation indicating that the cells supported endothelial tube formation. We interrogated the molecular response of the GFP-MCs to the angiogenic co-culture by qRT-PCR and found that the pericyte marker Ng2 was upregulated when the cells were co-cultured with HDMECs on NHDFs, indicating a change towards a perivascular phenotype. When GFP-MCs were cultured on the NHDF feeder layer, they upregulated the epithelial–mesenchymal transition marker Zeb1 and lost their circularity while increasing their size, indicating a change to a more migratory cell type. We analyzed the pericyte-like behavior of the GFP-MCs in a 3D cardiac microtissue (spheroid) with cardiomyocytes, cardiac fibroblasts and cardiac endothelial cells where the mesothelial cells showed alignment with the endothelial cells. These results indicate that mesothelial cells have the potential to adopt a perivascular phenotype and associate with endothelial cells to potentially support angiogenesis.
Dissertations / Theses on the topic "Fibroblastos NHDF"
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Jacob, Verónica Pereira. "Estudo da influência da idade dos fibroblastos em cultura na resposta ao 17ß-estradiol." Master's thesis, Universidade da Beira Interior, 2011. http://hdl.handle.net/10400.6/943.
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A cultura de células apresenta nos dias que correm uma importância indubitável, tratando-se de uma ferramenta de estudo frequentemente utilizada em várias áreas de investigação das Ciências da Saúde.
Os fibroblastos compreendem uma população de células heterogénea e dinâmica, amplamente distribuída pelos tecidos conjuntivos dos vertebrados, onde desempenham funções fulcrais na regulação estrutural e fisiológica dos tecidos. Por serem parte integrante da pele humana, apresentarem características favoráveis ao estabelecimento de culturas e por expressarem receptores específicos para neurotransmissores e hormonas, particularmente, receptores de estrogénio, os fibroblastos da derme humana, da linha celular NHDF, constituem um possível modelo de estudo da resposta ao 17β-estradiol (E2).
O principal objectivo deste trabalho consistiu no estudo da influência das passagens celulares, de culturas de fibroblastos NHDF, na resposta ao E2. Simultaneamente, também foi averiguada a interferência de diferentes condições de cultura na proliferação celular estimulada por estrogénio. Este estudo foi realizado em passagens celulares contíguas de fibroblastos NHDF, que foram expostos ao E2 por períodos de incubação crescentes (0, 48, 96 e 144 horas), na presença de meios de cultura diferentes na sua suplementação, nomeadamente: meio de cultura suplementado com 10 % de soro bovino fetal (FBS); meio de cultura sem FBS; e meio de cultura suplementado com 5% de FBS tratado com carvão activado. Para a quantificação da resposta dos fibroblastos ao E2 foi utilizado o ensaio de viabilidade celular baseado na redução do brometo de 3- (4,5-dimetil-2-tiazolil)-2,5-difenil-2H-tetrazólio (MTT), juntamente com o ensaio de exclusão de trypan blue.
Os resultados obtidos confirmam a influência das condições de cultura e da passagem celular nos estudos de resposta dos fibroblastos NHDF ao E2. Apenas foi verificada reprodutibilidade entre a resposta de quatro passagens celulares contíguas, quando os fibroblastos foram incubados por um período de 48 horas em meio suplementado com FBS. Adicionalmente, também foi este o meio de cultura onde se verificou existir maior correspondência entre os valores de absorvência de MTT e o número de células contabilizado. Por outro lado, somente foi visível uma proliferação significativa (P<0,05) dos fibroblastos em resposta à presença de E2 quando estes foram incubados em meio com FBS por 96 horas.
Uma vez que os melhores resultados foram obtidos nas culturas incubadas em meio com FBS, sugere-se que, através do ajuste do número de células com que se iniciam os estudos de resposta a estrogénios, poderá ser alcançado um equilíbrio entre a reprodutibilidade e sensibilidade demonstrada neste meio. Ainda assim, propõe-se que num procedimento ideal todas as experiências de um mesmo estudo deveriam ser efectuadas em células da mesma passagem.<br>Cell culture is of extreme importance nowadays, since it is a study tool often used in various
areas of research in Health Sciences.
The fibroblasts cover a heterogeneous and dynamic population of cells, widely distributed in
the connective tissues of vertebrates, where they have an important role in the structural
and physiological regulation of the tissues. The fibroblasts are an integral part of the human
skin, and present favorable characteristics to be cultured. Likewise, they express specific
receptors for neurotransmitters and hormones, particularly the estrogen receptors. Thus, the
human dermal fibroblasts of the NHDF cell line form a possible study model of response to
17β-estradiol (E2).
The main objective of this work consisted in the study of the influence of cell passages of the
NHDF fibroblast cultures, in response to E2. The interference of different culture conditions
in cell proliferation, by estrogen stimulation, was also studied. This study was carried out on
contiguous cell passages of NHDF fibroblasts, which were exposed to E2 with increasing
incubation periods (0, 48, 96 and 144 hours), in the presence of different culture medium
such as: (i) culture medium supplemented with 10% of fetal bovine serum (FBS); (ii) culture
medium without FBS; and (iii) culture medium supplemented with 5% charcoal Stripped FBS.
The response of the fibroblasts to E2 was quantified by the trypan blue exclusion assay and by
cell viability analysis, which is based on the reduction of 3- (4,5 -dimethyl-2-thiazolyl)-2,5-
diphenyl-2H-tetrazolium bromide (MTT assay).
The results confirm the influence of culture conditions and cell passage on the study of the
response of NHDF fibroblasts to E2.
The reproducibility between the response of four contiguous cell passages was verified, only
when the fibroblasts were incubated for a period of 48 hours in the culture medium
supplemented with FBS. In addition, it was also in this culture medium where there was a
better correspondence between the absorbance values of MTT and the number of counted
cells. On the other hand, there was a significant proliferation (P<0,05) of fibroblasts in
response to the presence of E2, when they were incubated in the culture medium with FBS
for 96 hours.
Since the best results were obtained in the culture medium with FBS, these results suggest
that, through the adjustment of the number of starting cells in the research studies of
response to estrogens, a balance between the reproducibility and sensibility demonstrated in
this medium may be achieved. Nevertheless, as a future prospective, the ideal procedure
should have all the experiences of the same study carried out on the same cell passage.
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Driemel, Heike [Verfasser], and Tim [Akademischer Betreuer] Maisch. "Untersuchungen zur Phototoxizität des wasserlöslichen Photosensibilisators Perinaphtenon (PNS) in Zellkulturen humaner dermaler Fibroblasten (NHDF) / Heike Driemel. Betreuer: Tim Maisch." Regensburg : Universitätsbibliothek Regensburg, 2011. http://d-nb.info/1022872516/34.
Full textConference papers on the topic "Fibroblastos NHDF"
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Espulgar, Wilfred, Fumiaki Shima, Ayami Hiura, et al. "Evaluation of Extracellular Matrix Influence to Beat Synchronicity of iPSC-derived Cardiomyocyte- NHC Fibroblast 3D Tissues Using Image Correlation Analysis." In JSAP-OSA Joint Symposia. Optica Publishing Group, 2017. http://dx.doi.org/10.1364/jsap.2017.5p_a409_5.
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Multicellular 3D cardiac microtissues composed of induced pluripotent stem cell (iPSC) derived cardiomyocytes and normal human cardiac fibroblasts (NHCFs) with different contractile performances are presented in this work. The cells were coated with fibronectin-gelatin nanofilm or collagen and then assembled using the developed cell accumulation technique to produce the multi-layered 3D tissues. The mixing ratio of NHCFs was adjusted to 0%, 25%, 50%, and 75% (iPS-CM100, iPS-CM75, iPS-CM50, iPS-CM25) of the total cell number. Using the image correlation analysis (Fig 1a-d), a non-invasive method, the effect of the amount of NHCF and the type of extra cellular matrix (ECM) coating used in the developed technique was determined. After 4 days of incubation, it was observed that the microtissue formed from the cells coated with collagen and with 25% NHCF had the best performance (Fig. 1e-f). However, further tests are still needed to determine if a lower amount of NHCF will have better performance and if it will be compatible with the host myocardium. Other tests are still needed to be done to determine the relationship of the histology to the observed contractile behavior. In addition, the presented data can be utilized in tuning the contractile behavior of the tissue by changing the ratio of iPS-CM and NHCF and cell surface coating depending on the desired behavior. With this, an alternative method for analyzing the engineered tissue and assessing the derived parameters were formulated which can be helpful in realizing the ideal cardiac tissue for transplant.
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Romero López, Yair, Nathalie Rosales Díaz Escobar, and Luis G. Vazquez de Lara. "Effect Of Surfactant Phospholipids On Collagen Expression (COL1A1) In Normal Human Lung Fibroblasts (NHLF)." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a3560.
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Wang, Hailong, Alexander A. Svoronos, Thomas Boudou, Jeffrey R. Morgan, Christopher S. Chen, and Vivek B. Shenoy. "Necking and Failure of Constrained Contractile 3D Microtissues: Role of Geometry and Stiffness." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14091.
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We report the discovery of a fundamental morphological instability of constrained 3D microtissues induced by a positive chemomechanical feedback between actomyosindriven contraction and the mechanical stresses arising from the constraints. Using a 3D model for mechanotransduction we find that perturbations in the shape of contractile tissues grow in an unstable manner leading to formation of “necks” where tensile stresses are sufficiently large to lead to the failure of the tissue by narrowing and subsequent elongation. The origin of the failure mechanism driven by active forces we report is distinct from the seemingly similar and well studied necking phenomena observed in “passive” materials due to elastic softening. Here the instability is caused by the active contraction (extension) of the regions of the tissue where the mechanical stresses are smaller (greater) than the characteristic actomyosin stall stress of the tissue. The magnitude of the instability is shown to be determined by the level of active contractile strain, the stiffness of the ECM and the stiffness of the boundaries that constrain the tissue. A phase diagram that demarcates stable and unstable behavior of 3D tissues as a function of these material parameters is derived. The predictions of our model are verified by analyzing the necking and failure of normal human fibroblast (NHF) tissue constrained in a loopended dogbone geometry and cardiac microtissues constrained between microcantilevers. In the former case, the tissue fails first by necking of the connecting rod of the dogbone followed by failure of the toroidal loops in agreement with our 3D finite element simulations. In the latter case we find that cardiac tissue is stable against necking when the density of the extra cellular matrix is increased and when the stiffness of the supporting cantilevers is decreased, also in excellent agreement with the predictions of our model. By analyzing the time evolution of the morphology of the constrained tissues we have quantitatively determined the chemomechanical coupling parameters that characterize the generation of active stresses in these tissues. More generally, the analytical and numerical methods we have developed provide a quantitative framework to study the biomechanics of cell to cellinteractions in complex 3D environments such as morphogenesis and organogenisis.