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Results for “Proliferation”

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PubMed2001

Quantitative analysis of the proliferation of epidermal cells using a human skin organ culture system and the effect of DbcAMP using markers of proliferation (BrdU, Ki-67, PCNA).

The process of re-epithelialization of a wound in the epidermis comprises the following steps: proliferation of epidermal basal cells, migration of epidermal cells to the wound surface, and cell differentiation. In the present study, we evaluated the proliferation of epidermal basal cells, an important process in wound healing, in the wound margin using a human skin organ culture system and immunohistochemical labeling with bromodeoxyuridine (BrdU), Ki-67, and proliferating cell nuclear antigen (PCNA), as markers of cell proliferation. Dibutyryl cyclic adenosine monophosphate (DbcAMP) is a derivative of cAMP and has been shown to modulate human keratinocyte proliferation. The proliferation of keratinocytes was promoted by DbcAMP and particularly strong effects in terms of BrdU labeling index, Ki-67-positive ratio, and PCNA-positive ratio, were seen at 10(-5) M. The skin organ culture system presented here uses adult preputial skin and is a simple technique that uses easily available materials. In addition to identifying S phase cells using BrdU as an index of cell proliferation, the immunohistochemical method for evaluating the expression of Ki-67 and PCNA is very simple. Accordingly, the method described here seems to be useful for evaluating cell dynamics in wound healing.

Biomarkers↗

PubMed1998

Hepatocyte proliferation in rats after ventromedial hypothalamic lesions: immunoreactivity patterns of proliferating cell nuclear antigen (PCNA).

Ventromedial hypothalamic (VMH) lesions result in increased DNA content in the rat liver. However, little information is available concerning the proliferative activity and lobular distribution of different cell populations in VMH-lesioned rat liver. The aim of the present study was to quantitatively assess these parameters in VMH-lesioned rat liver by measuring proliferating cell nuclear antigen (PCNA) reactivity. We investigated to determine whether this mitotic response involves acinar zones 1, 2, or 3. Changes in immunohistochemical labeling indices in rat liver were measured with an antibody against PCNA until 7 days after VMH lesioning. The effects of hepatic vagotomy on proliferation were also examined. Proliferation of hepatocytes in acinar zones 1-3 began to increase on day 1, and reached a maximum at 3 days. The area of most intense proliferation progressively shifted from acinar zone 1 to zone 3 in several days. The proliferation was completely inhibited by hepatic vagotomy, indicating that VMH lesions induce cell proliferation in rat liver via hepatic vagus nerve activity. This study implicates the information available on neural factors which initiate hepatocyte proliferation.

Animals↗

PubMed1995

Hepatocyte proliferation in primary biliary cirrhosis as assessed by proliferating cell nuclear antigen and Ki-67 antigen labelling.

Expression of the proliferating cell nuclear antigen and Ki-67 antigen by hepatocytes was investigated in liver tissue specimens of 29 patients with primary biliary cirrhosis (stage I 13, stage II 6, stage III 5 and stage IV 5 patients) prior to treatment with ursodeoxycholic acid and of five control subjects using immunocytochemical methods. Proliferating cell nuclear antigen and Ki-67 expression were reevaluated in seven patients after 3 years of treatment with ursodeoxycholic acid. Proliferating cell nuclear antigen labelling indices were significantly higher in primary biliary cirrhosis (stage I, 6.4% to 32.4%, median, 10.9%; stage II, 9.6% to 21.6%, median 11.4%; stage III, 5.2% to 12.5%, median, 7.6%; stage IV, 3.8% to 8.9%, median, 5.6%) than in controls (0% to 0.5%, median, 0.1%; p < 0.005). Ki-67 antigen labelling counts were lower than proliferating cell nuclear antigen indices but elevated in all stages of primary biliary cirrhosis (stage I, 0.5% to 3.5%, median 2.0%; stage II, 1.8% to 3.6%, median 2.6%; stage III, 1.3% to 2.5%, median 1.9%; stage IV, 0.4% to 1.7%, median 1.0%) compared with controls (0% to 0.5%, median 0.3%; p < 0.005). After ursodeoxycholic acid treatment, mean proliferating cell nuclear antigen and Ki-67 labelling indices decreased from a median of 9.0% (range, 3.8% to 32.4%) to a median of 7.8% (range, 4.5% to 17.2%; p = 0.045) for proliferating cell nuclear antigen and from a median of 2.5% (range, 0.8% to 3.6%) to a median of 2.1% (range, 0.9% to 3.1%; p = 0.031) for Ki-67 antigen. It is concluded that hepatocyte proliferation is markedly increased in primary biliary cirrhosis, particularly in the early stages of the disease, and that ursodeoxycholic acid treatment reduces proliferative activity in primary biliary cirrhosis.

Cell Division↗

PubMed1999

Topographical analysis of proliferating cells in meningiomas. Regional heterogeneity of the ability of tumors to proliferate.

Regional heterogeneity of the ability of tumors to proliferate has been pointed out, but its topographical analysis has not been studied in detail. To evaluate the distribution of highly proliferating cells in totally resected meningiomas, seven cases (including one recurrent case) were investigated in this study. Immunostaining of PCNA was performed on the sections crossing the equator of the tumors. These sections were divided into multi-squares with sides of 500 micrometers. The proliferating potential was determined as the PCNA positive cell count in each square. By painting those squares in eight kinds of color corresponding to the value of the PCNA positive cell count, maps of proliferative ability were made. To predict the localization of proliferating cells, we studied these maps in relation to the following: MR image, calcification, distance from the dural attachment and distance from the tumor capsule. Maps of the PCNA positive cell count showed the intra-tumoral heterogeneity of proliferative ability in all cases. Most of the cases showed homogeneous enhancement on MRIs and these images could not be a predicting factor of the highly proliferating area. There was no significant relationship between the calcification and the PCNA positive cell count. Although the proliferating ability was not correlated with the distance from the dural attachment, inner regions distant from the capsule showed higher proliferative ability in all cases. From these results, one should be aware that the information from the samples of meningiomas do not reflect the proliferating ability of the whole tumor.

Aged↗

PubMed2006

Peroxisome proliferator-activated receptor alpha and gamma ligands differentially affect smooth muscle cell proliferation and migration.

Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are expressed in smooth muscle cells (SMCs). This study was designed to compare the effects of PPARalpha and PPARgamma on SMC proliferation and migration and to determine how they operate. Treatment of SMCs from porcine coronary artery revealed that mitogen-stimulated DNA synthesis was blocked by the PPARalpha ligand 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (WY14,643) and 15-deoxy-Delta(12,14) prostaglandin J(2) (15d-PGJ(2)) (a putative PPARgamma agonist) but not by the PPARgamma agonist rosiglitazone or the PPARbeta/delta ligand 2-methyl-4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-thiazol-5-yl)-methylsulfanyl)phenoxy acetic acid (GW501516). Inhibition of DNA synthesis by clofibrate and 2-(4-(2-(1-cyclohexanebutyl-3-cyclohexylureido)ethyl)phenylthio)-2-methylproprionic acid (GW7647) confirmed that SMC proliferation is affected by PPARalpha. This conclusion was supported by the fact that WY14,643 also inhibited the proliferation of H4IIE hepatoma cells (expressing only PPARalpha) but not A10 SMCs (expressing only PPARgamma1). In contrast, the effective inhibition of all cell types with 15d-PGJ(2) indicated that this compound probably operates via a PPARgamma-independent mechanism. Interestingly, rosiglitazone did not inhibit DNA synthesis of either H4IIE or A10 cells, suggesting that the activation of PPARgamma does not influence cell proliferation. Phosphorylation of cyclin-dependent kinase 2 and expression of proliferating cell nuclear antigen were inhibited by WY14,643 but not by rosiglitazone or 15d-PGJ(2), indicating that PPARalpha prevents progression into S phase. Although rosiglitazone did not block SMC proliferation, it (like WY14,643) reduced neointimal hyperplasia in vitro. This observation can be rationalized by the fact that both WY14,643 and rosiglitazone inhibit SMC migration, probably through matrix metalloproteinase 9. Our study therefore shows that selective interference with mediators of cell cycle progression and cell migration via activation of PPARs may prevent growth-related vascular diseases such as restenosis and atherosclerosis.

Animals↗

PubMed2000

Proliferation markers, proliferating cell nuclear antigen, Ki67, 5-bromo-2'-deoxyuridine, and cyclin D1 in mouse olfactory epithelium.

We immunohistochemically identified proliferating cells in the olfactory epithelium of mice, using an anti-proliferating cell nuclear antigen (PCNA) antibody, an anti-Ki67 antibody, an anti-5-bromo-2'-deoxyuridine (BrdU) antibody, and an anti-cyclin D antibody. Positive cells stained by the 4 antibodies were identified mainly in the basal layer. The mean numbers of positive cells stained by the 4 antibodies in 500 olfactory epithelium cells from each animal were as follows: PCNA-positive cells 42, Ki67-positive cells 23, BrdU-positive cells 13.7, and cyclin D1-positive cells 9.2. PCNA may be detected in both proliferating and resting cells. Ki67 is an intranuclear antigen expressed in proliferating, but not resting, cells. Anti-BrdU antibodies might stain proliferating cells only following the S-phase, but not the G1-phase. Cyclin D1 is a protein that works during the G1-phase of the cell cycle. When we stain proliferating cells using proliferating cell markers, it is important to consider the cell cycle phases during which each marker stains.

Animals↗

PubMed1996

Antisense oligonucleotides to proliferating cell nuclear antigen and Ki-67 inhibit human mesangial cell proliferation.

Proliferating cell nuclear antigen (PCNA) and Ki-67 are cell cycle-associated nuclear proteins and are used as markers for proliferating cells. This study attempted to inhibit glomerular mesangial cell (MC) proliferation, which is the hallmark of many forms of glomerular disease, by inhibiting these nuclear proteins with antisense oligodeoxynucleotides. The antisense and sense phosphorothioate oligodeoxynucleotides complementary to PCNA and Ki-67 mRNA, including the initiation codon, were synthesized. Human MC were cultured in growth medium in the presence of sense or antisense oligodeoxynucleotides, and the effects of these oligodeoxynucleotides on mesangial cell proliferation were evaluated by direct cell count. Both PCNA and Ki-67 antisense oligodeoxynucleotides significantly inhibited mesangial cell proliferation as compared with sense oligodeoxynucleotides. Antisense oligodeoxynucleotides (10 microM) for PCNA and Ki-67 inhibited mesangial cell growth by greater than 50%. The effect of antisense oligodeoxynucleotides on target protein expression was examined by immunocytochemistry using specific monoclonal antibodies. Reverse transcription-polymerase chain reaction also was performed to evaluate the effect of antisense oligodeoxynucleotides on PCNA and Ki-67 mRNA expression. Studies of target protein and mRNA expression revealed that the inhibitory effects of the antisense oligonucleotides were mediated through decreases in the expression of both mRNA and protein. Sense oligodeoxynucleotides produced little effect. These results indicate that antisense oligodeoxynucleotides targeting PCNA and Ki-67 mRNA reduce the expression of these gene products and inhibit mesangial cell proliferation. Moreover, these results suggest the feasibility of antisense strategies designed to inhibit PCNA and Ki-67 expression for the inhibition of mesangial cell proliferation in vivo.

Cell Division↗

PubMed2005

[Role of peroxisome proliferators activated receptor gamma in mediating proliferation of rat vascular smooth muscle cells induced by advanced glycation end products].

OBJECTIVE: To observe the effect of pioglitazone on advanced glycation end products (AGEs)-induced proliferation of vascular smooth muscle cells (VSMCs) and expression of peroxisome proliferators activated receptor gamma (PPARgamma). To investigate the possible role of PPARgamma in mediating AGEs induced proliferation of VSMCs. METHODS: Primary cultures of smooth muscle cells from rat aorta were exposed to AGEs of different concentrations and different times prior to co-treatment with pioglitazone and AGEs. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay was adopted for the quantification of the cell proliferation ratio and PPARgamma expression was determined by RT-PCR and Western immunoblotting. RESULTS: AGEs increased the proliferation of VSMCs. AGEs treatment to VSMCs decreased mRNA and protein levels of PPARgamma in a time- and dose-related manner (P < 0.05). Pioglitazone inhibited the AGEs-induced proliferation of VSMCs in vitro. CONCLUSIONS: Activating PPARgamma in VSMCs, pioglitazone may play a role in anti atherosclerosis. The reduction in PPARgamma expression may be implicated in vascular smooth muscle cells proliferation and pathogenesis of atherosclerosis in patients with diabetes mellitus.

Animals↗

PubMed1995

Prognostic significance of cellular proliferation in renal cell carcinoma: a comparison of synthesis-phase fraction and proliferating cell nuclear antigen index.

DNA aneuploidy has repeatedly been shown to be a significant prognostic indicator in renal cell carcinoma; however, few studies have emphasized the importance of measurements of cellular proliferation. This study evaluated 55 patients treated by radical nephrectomy and for whom clinical follow-up was available. There were 36 men and 19 women with a mean age of 61 yr. Robson stage distribution was I, 38 cases; II, five cases; and III, 12 cases. Flow cytometric analysis in 44 cases revealed 29 DNA diploid and 15 DNA aneuploid tumors with a median synthesis-phase fraction (SPF) of 4.4% (range 1.0 to 31.4%). The median proliferating cell nuclear antigen index was 3.9% (range 0.1 to 58.0%). There was a significant correlation between SPF and proliferating cell nuclear antigen index (R = 0.769) in the 33 cases in which both were available. Cellular proliferation, as determined by SPF, was a significant prognostic indicator (P < 0.02), but proliferating cell nuclear antigen index did not correlate with outcome (P > 0.05). Other significant predictors in this study were Robson stage (P = 0.03) and nuclear grade (P = 0.0003). DNA ploidy did not correlate with outcome (P > 0.05). We conclude that cellular proliferation, as measured by SPF analysis, is a significant predictor of outcome for renal cell carcinoma. Although the proliferating cell nuclear antigen index correlated with SPF, it did not achieve statistical significance as a prognostic indicator.

Adult↗

PubMed1999

The proliferation-associated nuclear protein Ki-67 in the bovine system: partial characterisation and its application for determination of the proliferation of Theileria-infected bovine cells.

Theileria annulata-infected bovine cells as well as mitogen-stimulated bovine peripheral blood mononuclear cells (PBMC) express a proliferation-associated nuclear protein equivalent to the human Ki-67 protein. In analogy to the human system, the expression of the bovine Ki-67 protein is restricted to proliferating cells only, since (a) Ki-67 expression paralleled [3H]-thymidine incorporation in concanavalin A (Con A)-stimulated bovine PBMC, (b) Ki-67 was not detectable in quiescent bovine cells, and (c) Ki-67 expression in Theileria-infected cells is related to the presence of the parasites within the cytoplasm of the host cells; upon treatment with the theilericidal drug buparvaquone the parasites are destroyed and the cells cease to proliferate and to express the Ki-67 protein. Western-blot analysis of lysates of proliferating bovine cells revealed that the prototype monoclonal antibody Ki-67 and the new equivalent antibody MIB-1 detected one prominent protein band with an apparent molecular weight of 430 kDa. Two cDNA clones (pUC18.B1.Ki-67 and pUC18.B2.Ki-67) were isolated from a lambdagt11 cDNA library of T. annulata-infected bovine cells by immunoscreening with the monoclonal antibody MIB-1. Comparison of these cDNA sequences with those of the human Ki-67 protein revealed 60-70% identity. Within the "Ki-67 motif", identity proved to be 80% at the amino acid level. The remarkable identity between bovine and human Ki-67 proteins suggests that MIB-1 can be used as a marker for cell proliferation in animal research. In this context we could identify proliferating cells in lymph nodes of Theileria-infected animals and, furthermore, we could distinguish between infected and uninfected proliferating cells using MIB-1 and an antiserum against a recombinant parasite protein designated SA288.

Amino Acid Sequence↗

PubMed1984

Interleukin 2-driven T lymphocyte proliferation is dependent upon a surface antigen distinct from the interleukin 2 receptor: requirements for inhibition of T-cell proliferation by monoclonal antibody 5C3.

A monoclonal antibody (5C3) to an antigen expressed on activated guinea pig T lymphocytes that did not react with the interleukin 2 (IL-2) receptor, but inhibited IL-2-driven proliferative responses has been previously characterized. The present study provides further analysis of the inhibitory capacity of 5C3 for T-cell proliferation and of the relationship between the expression of the antigen defined by 5C3 and the capacity of cells to respond to IL-2. 5C3 inhibited proliferation of T-cell blasts to IL-2-containing fluids when added as late as 8 hr prior to termination of a 26-hr culture. 5C3 pretreatment of the IL-2-responsive blast cells was also sufficient to detect significant inhibition of proliferation. FACS analysis of these blasts indicated that maximal 5C3 binding was required for pretreatment to result in inhibition of IL-2-driven proliferation. Delayed addition of 5C3 to culture or pretreatment with 5C3 of responding cells also resulted in inhibition of proliferation of immune T lymphocytes to antigen-pulsed-presenting cells. Lastly, although modulated 5C3- blasts failed to proliferate to IL-2, induction of the 5C3-bearing molecule on these 5C3- blasts correlated with restoration of the ability of these cells to proliferate to IL-2. Collectively, these results further support the hypothesis that monoclonal antibody 5C3 interferes with a critical signal in the IL-2 growth pathway.

Animals↗

PubMed1991

A change in monokine requirements for proliferation during thymocyte maturation: co-stimulating activity of interleukin 6 in the proliferation of LYT2- and L3T4- thymocytes.

Interleukin 6 (IL-6) and interleukin 1 (IL-1) were compared as to their ability to induce the proliferation of distinct thymocyte subpopulations. IL-6 functions as a costimulator in IL-1- or IL-2-induced proliferation of adult double-negative (DN) thymocytes, whereas IL-6 alone failed to induce a significant level of proliferation. However, IL-6 alone induced significant proliferation of mature cortisone-resistant thymocytes, whereas IL-1 did not. Instead, IL-1 functioned as a co-stimulator in IL-6-induced proliferation of mature thymocytes. Finally, both IL-6 and IL-1 were capable of potentiating IL-2-induced proliferation of fetal DN thymocytes. These data suggest that the monokine requirements in thymocyte activation may vary during thymocyte maturation and that IL-6, when compared to IL-1, has a distinct effect on the proliferation of thymocytes.

Animals↗

PubMed1995

Rotenone, an anticarcinogen, inhibits cellular proliferation but not peroxisome proliferation in mouse liver.

In previous National Toxicology Program (NTP) studies, rotenone reduced the background incidence of hepatocellular carcinoma in male B6C3F1 mice. In the present studies, rotenone reduced the basal hepatic labeling index of male B6C3F1 mice in a dose-dependent fashion and inhibited hepatocellular proliferation, but not peroxisome proliferation, induced by the peroxisome proliferator Wy-14,643. These results indicate that reduction of hepatic tumors by rotenone may have been due to decreased liver cell replication, that peroxisome proliferation can be induced in the absence of hepatocellular proliferation and suggest rotenone as a potential tool in studies of relationships of cell proliferation, peroxisomal proliferation and hepatocarcinogenesis.

Animals↗

PubMed1998

Improved ELISA proliferation assay (EPA) for the detection of in vitro cell proliferation by a new Ki-67-antigen directed monoclonal antibody (Ki-S3).

We describe a simplified and improved proliferation assay based on a conventional ELISA system for the in vitro measurement of cellular proliferation (ELISA proliferation assay = EPA). The assay is based on a new monoclonal antibody (Ki-S3) to the proliferation-specific Ki-67-antigen and is carried out in 96-well microtiter plates using conventional immunoenzymatic methods. Ki-S3 is an immunoprecipitating monoclonal mouse IgG1 antibody, which recognizes a formalin-resistant epitope of the Ki-67 antigen. It can be used to measure proliferating cells in the cell cycle phases G1, S, G2 and M. In phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) the absorbance values obtained with the EPA show a statistically significant correlation to the number of Ki-S3 positive cells in simultaneously immunostained cytospin slides (r = 0.88). A direct comparison with [3H]thymidine labeling reveals the test to be an equally sensitive method for monitoring cellular proliferation (r = 0.91). This assay is an improved ELISA proliferation assay, which is easy to perform, does not require time-consuming pretreatments and avoids the hazards of radioactive isotopes.

Animals↗

PubMed2001

Proglucagon-derived peptides in intestinal epithelial proliferation: glucagon-like peptide-2 is a major mediator of intestinal epithelial proliferation in rats.

Proglucagon-derived peptides have been implicated in the control of intestinal mucosal cell division. To investigate the actions of these peptides on intestinal cell proliferation, different doses of enteroglucagon, oxyntomodulin, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) were tested in male Wistar rats maintained on total parenteral nutrition. Crypt cell proliferation was assessed by the analysis of arrested metaphases in microdissected crypts. Enteroglucagon and oxyntomodulin had no effect on intestinal weight or cell proliferation. GLP-1 had a slight effect on stomach and small intestinal weights and on epithelial cell proliferation in the small and large intestines. GLP-2 infusion dose-dependently increased the weights of the stomach, small intestine, colon, and cecum and increased crypt cell proliferation in the small and large intestines of parenterally fed rats. In orally fed animals, GLP-2 increased intestinal weight but had little effect on proliferation. Therefore, of the proglucagon-derived peptides, GLP-2 appears to be a major mediator of intestinal epithelial proliferation.

Animals↗

PubMed1998

Molecular basis of non-responsiveness to peroxisome proliferators: the guinea-pig PPARalpha is functional and mediates peroxisome proliferator-induced hypolipidaemia.

The guinea pig does not undergo peroxisome proliferation in response to peroxisome proliferators, in contrast with other rodents. To understand the molecular basis of this phenotype, the peroxisome proliferator activated receptor alpha (PPARalpha) from guinea-pig liver was cloned; it encodes a protein of 467 amino acid residues that is similar to rodent and human PPARalpha. The guinea-pig PPARalpha showed a high substitution rate: maximum likelihood analysis was consistent with rodent monophyly, but could not exclude rodent polyphyly (P approximately 0.06). The guinea-pig PPARalpha cDNA was expressed in 293 cells and mediated the induction of the luciferase reporter gene by the peroxisome proliferator, Wy-14,643, dependent on the presence of a peroxisome proliferator response element. Moreover the PPARalpha RNA and protein were expressed in guinea-pig liver, although at lower levels than in a species which is responsive to peroxisome proliferators, the mouse. To determine whether the guinea-pig PPARalpha mediated any physiological effects, guinea pigs were exposed to two selective PPARalpha agonists, Wy-14, 643 and methylclofenapate; both compounds induced hypolipidaemia. Thus the guinea pig is a useful model for human responses to peroxisome proliferators.

Amino Acid Sequence↗

PubMed1999

Commitment of neutrophilic differentiation and proliferation of HL-60 cells coincides with expression of transferrin receptor. Effect of granulocyte colony stimulating factor on differentiation and proliferation.

To examine the regulatory mechanisms of proliferation and maturation in neutrophilic lineage cells, we have tried to sort dimethyl sulfoxide (Me(2)SO)-treated HL-60 cells into transferrin receptor (Trf-R) positive (Trf-R(+)) and negative (Trf-R(-)) cells. Differentiated Trf-R(-) cells expressed more formyl-Met-Leu-Phe receptor (fMLP-receptor) and ability of O-(2) genaration, as markers of differentiation, than Trf-R(+) cells, and Trf-R(-) cell differentiation was markedly accelerated by the incubation with granulocyte colony stimulating factor (G-CSF). On the other hand, Trf-R(+) cells had a tendency to proliferate rather than differentiate, and proliferation was enhanced by G-CSF. These results indicate that Trf-R expression coincides with the commitment to proliferate or differentiate of HL-60 cells, and G-CSF accelerates these commitments. G-CSF-induced tyrosine phosphorylation of STAT 3 in Trf-R(-) cells much more than in Trf-R(+) cells. Protein 70 S6 kinase expression was higher in Trf-R(+) cells than in Trf-R(-) cells. Furthermore, p70 S6 kinase was hyperphosphorylated by G-CSF in Trf-R(+) cells, but not in Trf-R(-) cells. Rapamycin, an inhibitor of p70 S6 kinase activity, inhibited G-CSF-dependent proliferation of Trf-R(+) cells and increased fMLP-R expression on these cells. These results suggest that commitment to proliferation and differentiation in Me(2)SO-treated HL-60 cells is preprogrammed and correlated with Trf-R expression, and G-CSF potentiates the cellular commitment. STAT 3 may promote differentiation of Me(2)SO-treated HL-60 cells into neutrophils, while p70 S6 kinase may promote proliferation and negatively regulate neutrophilic differentiation.

Cell Differentiation↗

PubMed2005

Global analysis of endothelial cell line proliferation patterns based on nutrient-depletion models: implications for a standardization of cell proliferation assays.

It is known that cell populations growing in different environmental conditions may exhibit different proliferation patterns. However, it is not clear if, despite the diversity of the so-observed patterns, inherent cellular growth characteristics of the population can nevertheless be determined. This study quantifies the proliferative behaviour of the permanent endothelial human cell line, Eahy926, and establishes to which extent the estimation of the cell proliferation rate depends on variations of the experimental protocols. Cell proliferation curves were obtained for cells cultured over 16 days and the influences of cell seeding densities, foetal bovine serum content and frequency of culture medium changes were investigated. Quantitative dynamic modelling was conducted to evaluate the kinetic characteristics of this cell population. We proposed successive models and retained a nutrient-depletion toxicity dependant model, which takes into account the progressive depletion of nutrients, as well as the increase of toxicity in the cell culture medium. This model is shown to provide a very good and robust prediction of the experimental proliferation curves, whatever are the considered frequency of culture medium changes and serum concentrations. Thus, the model enables an intrinsic quantification of the parameters driving in vitro EAhy926 proliferation, including proliferation, nutrient consumption and toxicity increase rates, rather independently of the experiments design. We therefore propose that such models could provide a basis for a standardized quantification of intrinsic cell proliferation kinetics.

Cell Count↗