scholarly journals Effects of β-adrenergic receptor drugs on embryonic ventricular cell proliferation and differentiation and their impact on donor cell transplantation

2017 ◽  
Vol 312 (5) ◽  
pp. H919-H931 ◽  
Author(s):  
Tiam Feridooni ◽  
Adam Hotchkiss ◽  
Mark Baguma-Nibasheka ◽  
Feixiong Zhang ◽  
Brittney Allen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Transplantation ◽  
Adrenergic Receptor ◽  
Expression Profiles ◽  
Tritiated Thymidine ◽  
Graft Size ◽  
Mediated Effects ◽  
Ventricular Cells ◽  
Proliferation And Differentiation

β-Adrenergic receptors (β-ARs) and catecholamines are present in rodents as early as embryonic day (E)10.5. However, it is not known whether β-AR signaling plays any role in the proliferation and differentiation of ventricular cells in the embryonic heart. Here, we characterized expression profiles of β-AR subtypes and established dose-response curves for the nonselective β-AR agonist isoproterenol (ISO) in the developing mouse ventricular cells. Furthermore, we investigated the effects of ISO on cell cycle activity and differentiation of cultured E11.5 ventricular cells. ISO treatment significantly reduced tritiated thymidine incorporation and cell proliferation rates in both cardiac progenitor cell and cardiomyocyte populations. The ISO-mediated effects on DNA synthesis could be abolished by cotreatment of E11.5 cultures with either metoprolol (a β1-AR antagonist) or ICI-118,551 (a β2-AR antagonist). In contrast, ISO-mediated effects on cell proliferation could be abolished only by metoprolol. Furthermore, ISO treatment significantly increased the percentage of differentiated cardiomyocytes compared with that in control cultures. Additional experiments revealed that β-AR stimulation leads to downregulation of Erk and Akt phosphorylation followed by significant decreases in cyclin D1 and cyclin-dependent kinase 4 levels in E11.5 ventricular cells. Consistent with in vitro results, we found that chronic stimulation of recipient mice with ISO after intracardiac cell transplantation significantly decreased graft size, whereas metoprolol protected grafts from the inhibitory effects of systemic catecholamines. Collectively, these results underscore the effects of β-AR signaling in cardiac development as well as graft expansion after cell transplantation. NEW & NOTEWORTHY β-Adrenergic receptor (β-AR) stimulation can decrease the proliferation of embryonic ventricular cells in vitro and reduce the graft size after intracardiac cell transplantation. In contrast, β1-AR antagonists can abrogate the antiproliferative effects mediated by β-AR stimulation and increase graft size. These results highlight potential interactions between adrenergic drugs and cell transplantation.

scholarly journals Identification and In Vitro Expansion of Buccal Epithelial Cells

2018 ◽  
Vol 27 (6) ◽  
pp. 957-966
Author(s):  
Soraya Rasi Ghaemi ◽  
Bahman Delalat ◽  
Frances J. Harding ◽  
Yazad D. Irani ◽  
Keryn A. Williams ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Transplantation ◽  
Progenitor Cell ◽  
Ex Vivo ◽  
Seeding Density ◽  
Cell Seeding ◽  
Cell Marker ◽  
Cell Seeding Density ◽  
Proliferation And Differentiation

Ex vivo-expanded buccal mucosal epithelial (BME) cell transplantation has been used to reconstruct the ocular surface. Methods for enrichment and maintenance of BME progenitor cells in ex vivo cultures may improve the outcome of BME cell transplantation. However, the parameter of cell seeding density in this context has largely been neglected. This study investigates how varying cell seeding density influences BME cell proliferation and differentiation on tissue culture polystyrene (TCPS). The highest cell proliferation activity was seen when cells were seeded at 5×104 cells/cm2. Both below and above this density, the cell proliferation rate decreased sharply. Differential immunofluorescence analysis of surface markers associated with the BME progenitor cell population (p63, CK19, and ABCG2), the differentiated cell marker CK10 and connexin 50 (Cx50) revealed that the initial cell seeding density also significantly affected the progenitor cell marker expression profile. Hence, this study demonstrates that seeding density has a profound effect on the proliferation and differentiation of BME stem cells in vitro, and this is relevant to downstream cell therapy applications.

scholarly journals Chronic stress promotes gastric cancer progression and metastasis: an essential role for ADRB2

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Xuan Zhang ◽  
Yi Zhang ◽  
Zhongyuan He ◽  
Kai Yin ◽  
Bowen Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Chronic Stress ◽  
Adrenergic Receptor ◽  
Tumour Growth ◽  
Mapk Pathway ◽  
Rt Pcr ◽  
Expression Levels

Abstract An increasing number of studies indicate that adrenergic signalling plays a fundamental role in chronic stress-induced tumour progression and metastasis. However, its function in gastric cancer (GC) and its potential mechanisms remain unknown. The expression levels of β-adrenergic receptor (ADRB) in GC cell lines were examined by using real-time polymerase chain reaction (RT-PCR) and western blotting. The effects of β2 adrenergic receptor (ADRB2) activation and blockade were investigated in vitro in GC cells by using proliferation, migration, invasion, cell cycle and apoptosis assays. Chronic restraint stress (CRS) increased the plasma levels of catecholamines and cortisol and also induced progression and metastasis of GC in vivo. Furthermore, immunohistochemical staining and a TUNEL assay were employed to observe the regulation of cell viability in vivo. The expression levels of ADRB2 in 100 human GC samples were measured by RT-PCR and immunohistochemistry. The stress hormones epinephrine and norepinephrine significantly accelerated GC cell proliferation, invasion and viability in culture, as well as tumour growth in vivo. These effects were reversed by the ADRB antagonists propranolol and ICI118,551 (an ADRB2-specific antagonist). Moreover, the selective ADRB1 antagonist atenolol had almost no effect on tumour cell proliferation and invasion in vitro and in vivo. ADRB2 antagonists suppressed proliferation, invasion and metastasis by inhibiting the ERK1/2-JNK-MAPK pathway and transcription factors, such as NF-κB, AP-1, CREB and STAT3. Analysis of xenograft models using GC cells revealed that ADRB2 antagonists significantly inhibited tumour growth and metastasis, and chronic stress antagonized these inhibitory effects. In addition, chronic stress increased the expression of VEGF, MMP-2, MMP-7 and MMP-9 in transplanted tumour tissue, and catecholamine hormones enhanced the expression of metastasis-related proteins. The expression of ADRB2 was upregulated in tumour tissues and positively correlated with tumour size, histological grade, lymph node metastasis and clinical stage in human GC samples. Stress hormone-induced activation of the ADRB2 signalling pathway plays a crucial role in GC progression and metastasis. These findings indicate that ADRB2 signalling regulates GC progression and suggest β2 blockade as a novel strategy to complement existing therapies for GC.

scholarly journals MicroRNA-99b predicts clinical outcome of osteosarcoma and suppresses tumor cell proliferation, migration and invasion

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xin Shi ◽  
Xingfa Guan
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Prognostic Value ◽  
Cox Regression ◽  
Expression Profiles ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Cox Regression Analysis ◽  
Normal Tissues

Abstract Background Osteosarcoma (OS) is a malignancy predominantly occurred in children and adolescents. Numerous microRNAs are involved in the pathogenesis of various cancers. This study aimed to investigate the expression profiles of miR-99b and its prognostic value in OS patients, and further analyze the biological function of miR-99b in the tumor progression by using OS cells. Methods Expression of miR-99b was measured using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were performed to evaluate the prognostic value of miR-99b. OS cell lines were used to investigate the effects of miR-99b on cell proliferation, migration and invasion. Results A significant decreased expression of miR-99b was observed in the OS tissues and cell lines respectively compared with the normal tissues and cells. Aberrant expression of miR-99b was associated with the patients’ metastasis and TNM stage, and could be used to predict the prognosis of OS. The expression of miR-99b was regulated in vitro by cell transfection, and we found that the overexpression of miR-99b led to suppressed cell proliferation, migration and invasion, whereas the knockdown of miR-99b resulted in the opposite results. Conclusions In one word, the aberrantly expressed miR-99b serves a prognostic biomarker for OS patients. OS cell proliferation, migration and invasion can be inhibited by the overexpression of miR-99b, suggesting that the methods to increase miR-99b expression may be novel therapeutic strategies in OS.

‘In vivo’ and ‘in vitro’ activity of Larrea divaricata Cav. on EL-4 cells

2010 ◽  
Vol 30 (8) ◽  
pp. 965-971 ◽  
Author(s):  
Roberto Davicino ◽  
Rosario Alonso ◽  
Claudia Anesini
Keyword(s):  
Cell Proliferation ◽  
Aqueous Extract ◽  
Tritiated Thymidine ◽  
Folk Medicine ◽  
Thymidine Uptake ◽  
Stimulatory Action ◽  
T Lymphoma ◽  
Larrea Divaricata

Larrea divaricata is a plant widely used in folk medicine in Argentina. It has been demonstrated that an aqueous extract of L. divaricata possesses a biphasic effect on cell proliferation, at low concentrations exerts a stimulatory action and at high concentrations exerts anti-proliferative effects upon the T lymphoma BW 5147; therefore, we propose in this paper to test the effect of the extract ‘in vitro’ and ‘in vivo’ in another T-cell lymphoma named EL-4. It was analyzed ‘in vitro’ cell proliferation by tritiated thymidine uptake and the effect of the extract on tumors induced in mice analyzing tumor progression and survival.The results showed that the aqueous extract induced the proliferation of tumor cells at all the concentrations studied. The results ‘in vivo’ showed that the aqueous extract stimulated significantly the size of tumors and that untreated mice lived longer than those treated. It is important to be very careful when plant extracts are selected for the treatment of several diseases. Consequently, before using a plant extract, specific scientific studies must be undertaken on different models to certificate therapeutic and adverse effects. Moreover, it can be said that L. divaricata has a specific anti-tumor mechanism of action depending on the targets.

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