Concentrations Of Stem Cell Factor Research Articles

Effects of stem cell factor in follicular fluid and granulosa cells on oocyte maturity and clinical pregnancy.

Stem cell factor (SCF) is implicated in cell growth, proliferation, differentiation, migration, and apoptosis. SCF in follicular fluid (FF) and granulosa cells (GCs) plays a key role in oocyte maturation and clinical pregnancy; however, the exact mechanism is unclear. We aimed to investigate SCF potential in predicting oocyte maturity and clinical pregnancy. We collected 60 FF and 60 GCs samples from different patients with infertility. Real-time polymerase chain reaction and cellular immunofluorescence analyses were used to quantitatively and qualitatively determine SCF concentration in GCs; enzyme-linked immunosorbent assay was used to determine SCF concentration in FF. GC and FF SCF concentrations were positively correlated with metaphase (M)II oocyte proportion and clinical pregnancy (R = 0.280, 0.735 vs R = 0.257, 0.354). SCF concentrations in GCs were significantly higher in the clinical pregnancy group than in the nonclinical pregnancy group. Immunofluorescence analysis showed that SCF expression was higher in the clinical pregnancy and high-MII -oocyte proportion groups. Receiver operating characteristic curve analysis showed that combined SCF and serum anti-Müllerian hormone levels could predict oocyte maturity and clinical pregnancy better than either of these factors alone. SCF concentration in GCs and FF can serve as a predictor of oocyte maturity and clinical pregnancy.

Deep immune profiling of patients with renal impairment unveils distinct immunotypes associated with disease severity.

Chronic kidney disease (CKD) is pathologically correlated with a sophisticated milieu of innate and adaptive immune dysregulation, but the underlying immunological disturbances remain poorly understood. To address this, we comprehensively interrogated cellular and soluble elements of the immune system by using high-dimensional flow cytometry to analyze peripheral blood mononuclear cells and performing cytokine/chemokine profiling of serum samples, respectively, in a cohort of 69 patients and 19 non-CKD controls. Altered serum levels of several cytokines/chemokines were identified, among which concentrations of stem cell factor (SCF) were found to be elevated with the progression of CKD and inversely correlated with estimated glomerular filtration rate (eGFR). Deep immunophenotyping analyses reveal a global change in immune modulation associated with CKD severity. Specifically, a decrease in the subsets of CD56dim natural killer (NK) cells (KLRG-1+CD38+CD64+CD15+CD197+) and monocytes (KLRG-1+CD38+PD-1+) was detected in severe CKD compared with controls and mild CKD. In addition, comparisons between mild and severe CKD demonstrated a loss of a mature B cell population (PD-1+CD197+IgD+HLA-DR+) in the advanced stages of disease. Further, we identified immunophenotypic markers to discriminate mild CKD from the controls, among which the portion of CD38+ monocytes was of particular value in early diagnosis. Our data unveil severity-specific immunological signatures perturbed in CKD patients.

Exploration of serum biomarkers in dogs with malignant melanoma receiving anti-PD-L1 therapy and potential of COX-2 inhibition for combination therapy

Immune checkpoint inhibitors (ICIs) such as anti-PD-L1 antibodies are widely used to treat human cancers, and growing evidence suggests that ICIs are promising treatments for canine malignancies. However, only some canine oral malignant melanoma (OMM) cases respond to ICIs. To explore biomarkers predictive of survival in dogs with pulmonary metastatic OMM receiving the anti-PD-L1 antibody c4G12 (n = 27), serum concentrations of prostaglandin E2 (PGE2), cytokines, chemokines, and growth factors were measured prior to treatment initiation. Among 12 factors tested, PGE2, interleukin (IL)-12p40, IL-8, monocyte chemotactic protein-1 (MCP-1), and stem cell factor (SCF) were higher in OMM dogs compared to healthy dogs (n = 8). Further, lower baseline serum PGE2, MCP-1, and vascular endothelial growth factor (VEGF)-A concentrations as well as higher IL-2, IL-12, and SCF concentrations predicted prolonged overall survival. These observations suggest that PGE2 confers resistance against anti-PD-L1 therapy through immunosuppression and thus is a candidate target for combination therapy. Indeed, PGE2 suppressed IL-2 and interferon (IFN)-γ production by stimulated canine peripheral blood mononuclear cells (PBMCs), while inhibition of PGE2 biosynthesis using the COX-2 inhibitor meloxicam in combination with c4G12 enhanced Th1 cytokine production by PBMCs. Thus, serum PGE2 may be predictive of c4G12 treatment response, and concomitant use of COX-2 inhibitors may enhance ICI antitumor efficacy.

Chitosan Tubes Inoculated with Dental Pulp Stem Cells and Stem Cell Factor Enhance Facial Nerve-Vascularized Regeneration in Rabbits.

Facial nerve injury is a common clinical condition that leads to disfigurement and emotional distress in the affected individuals, and the recovery presents clinical challenges. Tissue engineering is the standard method to repair nerve defects. However, nerve regeneration is still not satisfactory because of poor neovascularization after implantation, especially for the long-segment nerve defects. In the current study, we aimed to investigate the potential of chitosan tubes inoculated with stem cell factor (SCF) and dental pulp stem cells (DPSCs) in facial nerve-vascularized regeneration. In the in vitro experiment, DPSCs were isolated, cultured, and then identified. The optimal concentration of SCF was screened by CCK8. Cytoskeleton and living-cell staining, migration, CCK8 test, and neural differentiation assays were performed, revealing that SCF promoted the biological activity of DPSCs. Surprisingly, SCF increased the neural differentiation of DPSCs. The migration and angiogenesis experiments were carried out to show that SCF promoted the angiogenesis and migration of human umbilical vein endothelial cells (HUVECs). In the facial nerve, 7 mm defects of New Zealand white rabbits, hematoxylin–eosin (HE), immunohistochemistry, toluidine blue staining, and transmission electron microscopy observation were performed at 12 weeks postsurgery to show more nerve fibers and better myelin sheath in the SCF + DPSC group. In addition, the whisker movements, Masson’s staining, and western blot assays were performed, demonstrating functional repair and that the expression level of CD31 protein in the group SCF + DPSCs was relatively close to that in the group Autograft. In summary, chitosan tubes inoculated with SCF and DPSCs increased neurovascularization and provided an effective method for repairing facial nerve defects, indicating great promise for clinical application.

Systems genetics in the rat HXB/BXH family identifies Tti2 as a pleiotropic quantitative trait gene for adult hippocampal neurogenesis and serum glucose.

Neurogenesis in the adult hippocampus contributes to learning and memory in the healthy brain but is dysregulated in metabolic and neurodegenerative diseases. The molecular relationships between neural stem cell activity, adult neurogenesis, and global metabolism are largely unknown. Here we applied unbiased systems genetics methods to quantify genetic covariation among adult neurogenesis and metabolic phenotypes in peripheral tissues of a genetically diverse family of rat strains, derived from a cross between the spontaneously hypertensive (SHR/OlaIpcv) strain and Brown Norway (BN-Lx/Cub). The HXB/BXH family is a very well established model to dissect genetic variants that modulate metabolic and cardiovascular diseases and we have accumulated deep phenome and transcriptome data in a FAIR-compliant resource for systematic and integrative analyses. Here we measured rates of precursor cell proliferation, survival of new neurons, and gene expression in the hippocampus of the entire HXB/BXH family, including both parents. These data were combined with published metabolic phenotypes to detect a neurometabolic quantitative trait locus (QTL) for serum glucose and neuronal survival on Chromosome 16: 62.1-66.3 Mb. We subsequently fine-mapped the key phenotype to a locus that includes the Telo2-interacting protein 2 gene (Tti2)-a chaperone that modulates the activity and stability of PIKK kinases. To verify the hypothesis that differences in neurogenesis and glucose levels are caused by a polymorphism in Tti2, we generated a targeted frameshift mutation on the SHR/OlaIpcv background. Heterozygous SHR-Tti2+/- mutants had lower rates of hippocampal neurogenesis and hallmarks of dysglycemia compared to wild-type littermates. Our findings highlight Tti2 as a causal genetic link between glucose metabolism and structural brain plasticity. In humans, more than 800 genomic variants are linked to TTI2 expression, seven of which have associations to protein and blood stem cell factor concentrations, blood pressure and frontotemporal dementia.

Existence of multiple organ aging in animal model of emphysema induced by cigarette smoke extract.

INTRODUCTIONIt is commonly considered that COPD or at least emphysema represents accelerated lung aging induced in part by oxidative damage from cigarette smoke components. However, the issue if there are any aging signs in other organs in patients with COPD or emphysema remains unclear. The aim of this study is to explore whether there is multiple organ aging in the animal model of emphysema induced by cigarette smoke extract (CSE), and to ascertain the possible mechanisms, if any.METHODSThe animal model of emphysema was induced by CSE. Histomorphological changes in lung, heart, liver, kidney and spleen tissues were measured after staining with hematoxylin and eosin (H&E). The concentrations of stem cell factor (SCF), CyclinD1 and superoxide dismutase (SOD) in serum were determined by ELISA kit. The expressions of p16 (INK4a), Sca-1, eNOS proteins and mRNA in lung, heart, liver, kidney and spleen tissues were detected by Western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), respectively. Decitabine (Dec) was applied to examine whether it could alter the changes caused by CSE.RESULTSThe histomorphology of lung tissue was significantly changed, while other organs exhibited normal structure and histomorphology. The concentrations of SCF, CyclinD1 and SOD in serum were lower in the CSE group than in the control group. The expression levels of p16(INK4a) protein and mRNA in lung, heart, liver, kidney and spleen tissues were higher in the CSE group than in the control group, while the expression levels of Sca-1 and eNOS proteins and mRNA were lower in the CSE group than in the control group, in the tissues described above. Dec could partly alleviate the damages caused by CSE and the degree of alleviation resulted by Dec varied from organ to organ.CONCLUSIONSIn addition to the aging of the lung tissue in the emphysema animal model induced by CSE, the tissues of the heart, liver, kidney and spleen were also in the progress of aging, but the sensibility and affinity of lung to CSE were higher than those of the other organs. Multiple organ aging may also exist in the animal model of emphysema induced by CSE. DEC can partly alleviate the multiple organ aging caused by CSE.

The association of stem cell factor and soluble c-Kit (s-cKit) receptor serum concentrations with the severity and risk prediction of autism spectrum disorders.

S tem cell factor (SCF) and its receptor (c-kit) signaling play important role in normal brain physiology including neurogenesis, synapse formation and spatial learning function of the hippocampal region of the brain. Autism spectrum disorder (ASD) is believed to result from abnormal development of neuronal networks and synaptic function. The aim of this study was to evaluate the SCF and its soluble receptor (s-ckit) serum concentrations in ASD. We also studied the serum SCF and s-ckit concentration with the severity of ASD (Levels 1-3; Mild, Moderate and severe, respectively). Ninety five patients with ASD (Mild; n=33, Moderate; n=32 and severe; n=30) and 82 normal controls age matched were included in this study. The serum concentration of SCF and s-ckit were measured by enzyme-linked immunosorbent assay (ELISA). The SCF serum concentration in control subjects was 3.45±1.06 ng/ml and in ASD was 3.41±0.92 ng/ml (P=0.88). The serum levels of s-ckit in control and ASD groups were 56.82±13.22 ng/ml and 67.11±12.00, respectively (P=001). We have also studied serum SCF and s-ckit concentrations with the severity of ASD. The serum concentration of SCF in mild, moderate and severe ASD groups was 3.45±0.93, 3.4±0.87 and 3.43±0.98 ng/ml, respectively (P>0.05) and for s-ckit was 48.77±9.28, 61.66±12.18 and 93.11±14.81ng/ml, respectively (P<0.05). The result of this study suggests that serum s-cKit concentrations may provide a reliable and practical indicator of ASD and positively correlated with disease severity. It is also concluded that s-cKit might be involved in the pathophysiology of ASD.

Possible Role of Circulating Bone Marrow Mesenchymal Progenitors in Modulating Inflammation and Promoting Wound Repair.

Circulating bone marrow mesenchymal progenitors (BMMPs) are known to be potent antigen-presenting cells that migrate to damaged tissue to secrete cytokines and growth factors. An altered or dysregulated inflammatory cascade leads to a poor healing outcome. A skin model developed in our previous study was used to observe the immuno-modulatory properties of circulating BMMP cells in inflammatory chronic wounds in a scenario of low skin perfusion. BMMPs were analysed exclusively and in conjunction with recombinant tumour necrosis factor alpha (TNFα) and recombinant hepatocyte growth factor (HGF) supplementation. We analysed the expression levels of interleukin-8 (IL-8) and ecto-5′-nucleotidase (CD73), together with protein levels for IL-8, stem cell factor (SCF), and fibroblast growth factor 1 (FGF-1). The successfully isolated BMMPs were positive for both hemopoietic and mesenchymal markers and showed the ability to differentiate into adipocytes, chondrocytes, and osteocytes. Significant differences were found in IL-8 and CD73 expressions and IL-8 and SCF concentrations, for all conditions studied over the three time points taken into consideration. Our data suggests that BMMPs may modulate the inflammatory response by regulating IL-8 and CD73 and influencing IL-8 and SCF protein secretions. In conclusion, we suggest that BMMPs play a role in wound repair and that their induced application might be suitable for scenarios with a low skin perfusion.

Tissue distribution of stem cell factor in adults

Stem cell factor (SCF) is an essential cytokine during development and is necessary for gametogenesis, hematopoiesis, mast cell development, stem cell function, and melanogenesis. Here, we measure SCF concentration and distribution in adult humans and mice using gene expression analysis, tissue staining, and organ protein lysates. We demonstrate continued SCF expression in many cell types and tissues into adulthood. Tissues with high expression in adult humans included stomach, spleen, kidney, lung, and pancreas. In mice, we found high SCF expression in the esophagus, ovary, uterus, kidney, and small intestine. Future studies may correlate our findings of increased, organ-specific SCF concentrations within adult tissues with increased risk of SCF/CD117-related disease.

Fetal Hemoglobin Induction with Forced Chromatin Looping in Gene-Modified Erythroid Cells Differentiated from Rhesus Hematopoietic Progenitor Cells

Substantial advances in genome engineering offer new therapies for hemoglobin (Hb) disorders including sickle cell disease. Fetal hemoglobin reactivation remains a viable strategy, as recently demonstrated in human erythroid cells with an artificial looping molecule ZF-Ldb1, tethering Ldb1 to the γ-globin promoter by specific zinc finger proteins (Deng et al., 2014). Large animal preclinical testing can improve the therapeutic potential of such approaches by optimizing safety and efficacy issues before launching clinical trials in humans. A robust in vitro erythroid evaluation system, however, does not exist to determine if fetal hemoglobin reactivation can be modeled in the rhesus macaque. Therefore, in the current work, we aimed to develop an efficient in vitro erythroid differentiation model from rhesus hematopoietic progenitor cells with Hb production at detectable protein levels, and to evaluate rhesus fetal hemoglobin reactivation with ZF-Ldb1.To adapt a human erythroid differentiation method to rhesus cells, we used C3H or OP9 feeder cells to culture rhesus peripheral blood mononuclear cells (PBMCs) with HEMA differentiation media containing 10ng/ml stem cell factor (SCF), 1ng/ml interleukin-3 (IL3), 2U/ml erythropoietin (Epo), and 20% fetal bovine serum (FBS) (Migliaccio et al., 2010). Two weeks after erythroid differentiation, robust Hb production evaluated by HB electrophoresis was obtained on both C3H and OP9 feeder cells but not in feeder-free conditions. Increased concentration of SCF (20x), IL3 (10x), and Epo (1.5x) allowed for Hb production even in feeder-free conditions; however, fetal Hb was predominant (due to 20x SCF). Both conditions provided similar levels of enucleation (39±6.3% vs 29±5.6%, ns), indicating efficient differentiation. We then compared HEMA media with serum-free StemSpan-based differentiation media to evaluate transduction with a GFP-encoding lentiviral vector at MOI 2.5 two days after initiating differentiation. Transduction was almost completely inhibited (0.4±0.5%) in HEMA media, while StemSpan-based transduction media followed by HEMA differentiation media resulted in significant increase of transduction efficiency (41±8.5%, p<0.01). These data demonstrate that feeder cells are required for rhesus erythroid differentiation in HEMA media, while FBS strongly interferes lentiviral transduction.Next, we sought to establish a reverse phase HPLC method to quantitatively analyze rhesus globins among differentiated erythroid cells. Peaks on the HPLC chromatogram were eluted and run in liquid chromatography-mass spectrometry (LC/MS) and tandem mass spectrometry (MS/MS) for protein identification. We identified β-globin and γ-globin (HBG1 and HBG2) peaks using both rhesus peripheral blood (99±26% and 0.65±0.28%) and in vitro differentiated rhesus erythroid cells (63±13% and 37±16%), which is essential for Hb switching analysis. In addition, human β-globin and T87Q β-globin (with anti-sickling mutation) proteins were also separated from rhesus globins in the HPLC chromatogram and were detectable for quantitation.Finally, we evaluated whether fetal Hb expression can be induced by the ZF-Ldb1 molecule in rhesus erythroid cells. We transduced differentiating rhesus CD34+ cells with ZF-Ldb1-encoding lentiviral vectors that are driven by an erythroid specific ankyrin-1 promoter, and contain GFP along with a β-globin locus control region (LCR) enhancer or YFP without the LCR. After erythroid differentiation, we obtained both LCR/ZF-Ldb1/GFP+ (9.4%) and ZF-Ldb1/YFP+ (1.3%) rhesus erythroid cells, and higher γ-globin RNA expression was detected for GFP+ and YFP+ fractions (68.1±1.5% and 59.8±2.1%, respectively), as compared to GFP- and YFP- controls (28.1±3.1% and 31.8±1.9%, p<0.05). These data demonstrate successful γ-globin induction with ZF-Ldb1 vectors in the rhesus macaque.In conclusion, we developed an efficient rhesus erythroid cell differentiation protocol from hematopoietic progenitor cells with robust Hb production detectable at protein levels, analyzed in a newly established HPLC method. The ZF-Ldb1 vector transduction allows for induction of γ-globin expression in rhesus erythroid cells. Further studies are warranted to optimize gene modification and transplantation of rhesus hematopoietic progenitor cells. DisclosuresNo relevant conflicts of interest to declare.

Plasminogen activator inhibitor type-1 is a negative regulator of hematopoietic regeneration in the adipocyte-rich bone marrow microenvironment

Bone marrow adipocytes (BMAs) have recently been recognized as a niche component with a suppressive function. Obese individuals with abundant BMAs exhibit impaired hematopoietic regeneration after hematopoietic stem cell transplantation (HSCT). We hypothesized that plasminogen activator inhibitor type-1 (PAI-1), an adipokine that regulates the fibrinolytic system, contributes to impaired hematopoiesis in bone marrow (BM) microenvironment with abundant BMAs. We demonstrated that BMAs differentiated in vitro could secrete PAI-1 and were positive for PAI-1 in vivo. In addition, the abundance of BMAs was associated with high levels of PAI-1 expression. The BMA-rich microenvironment exhibited impaired hematopoietic regeneration after HSCT when compared with a BMA-less microenvironment. The impaired hematopoietic regeneration in BMA-rich microenvironment was significantly alleviated by PAI-1 knockout or PAI-1 inhibitor treatment. Obese mice with abundant BMAs, compared with normal-weight mice, exhibited higher bone marrow PAI-1 concentrations, increased fibrinolytic system suppression, and lower stem cell factor (SCF) concentrations after HSCT. PAI-1 inhibitor administration significantly activated the fibrinolytic system in obese mice, contributing to the higher SCF concentration. Moreover, PAI-1 inhibitor treatment significantly alleviated the impaired hematopoietic regeneration in obese mice both after 5-fluorouracil injection and HSCT. These results indicate that PAI-1 hinders hematopoietic regeneration in BMA-rich microenvironments. The blockade of PAI-1 activity could be a novel therapeutic means of facilitating hematopoietic reconstitution in BMA-rich patients.

Divergent Mononuclear Cell Participation and Cytokine Release Profiles Define Hip and Knee Osteoarthritis.

Osteoarthritis (OA) is a progressive joint disease driven by a blend of inflammatory and biomechanical processes. Studies using human samples to understand inflammatory mechanisms in OA frequently recruit OA patients with different affected joints, even though recent evidence indicates that OA is a heterogeneous disease which only culminates in a common end point. Differences in age of onset and the dynamics of disease progression suggest that different joints may represent different disease entities, thereby diluting the discovery potential in a combined analysis. We hypothesized that different OA joints may also differ in immunopathology within the synovium. To investigate this hypothesis, we profiled the immune cell contribution (flow cytometry) and cytokine release profiles (ELISA) in purified synovial membrane mononuclear cells from 50 patients undergoing either hip (n = 34) or knee (n = 16) replacement surgery. Unsupervised computational approaches were used for disease deconstruction. We found that hip and knee osteoarthritis are not identical in respect to the inflammatory processes that take place in the synovial membrane. Instead, we report that principally CD14+ macrophages are expanded fourfold in the synovial membrane of patients with knee OA compared to hip OA, with a trend to higher expression in CD8+ T cells, while CD4+ T cells, B cells, and NK cells were found at comparable quantities. Upon isolation and culture of cells from synovial membrane, isolates from hip OA released higher concentrations of Eotaxin (CCL11), G-CSF, GM-CSF, INF-γ, IP-10 (CXCL10), TNF-α, MIP-1α (CCL3), MIP-1β (CCL4), IL-4, IL-10, IL-17, and lower concentrations of stem cell factor (SCF), thereby highlighting the difference in the nature of hip and knee osteoarthritis. Taken together, this study establishes hip and knee OA as immunologically distinct types of OA, and creates a resource of the cytokine expression landscape and mononuclear cell infiltration pattern of patients with hip and knee osteoarthritis.

Serum level of stem cell factor and its soluble receptor in aspirin-exacerbated respiratory disease

Aim: Stem cell factor (SCF) may be associated with inflammatory processes leading to aspirin-induced asthma. This study evaluated the relationship between serum level of SCF and its soluble receptor with aspirin-induced asthma. Methods & materials: Twenty-five patients and 25 healthy controls were enrolled in this study. The concentration of SCF and mast/stem cell growth factor receptor (C-kit) was determined in serum samples. Spirometry and rhinometry were performed to determine the severity of the disease. p < 0.05 were considered significant. Results: The serum levels of SCF and C-kit receptor were significantly higher in the case group. The serum SCF and C-kit level had a significant positive correlation with the severity of asthma, disease duration and nasal obstruction. Conclusion: Our findings suggest that SCF and C-kit receptors have a direct effect on the severity of aspirin-induced asthma.

Increased SCF in Follicular Fluid and Granulosa Cells Positively Correlates With Oocyte Maturation, Fertilization, and Embryo Quality in Humans.

Stem cell factor (SCF), which is derived from granulosa cells (GCs), plays a key role in the process of follicular development and oocyte maturation. The present study aimed to explore whether the levels of SCF in follicular fluid (FF) and GCs can be used as a potential marker for predicting oocyte developmental potential. Follicular fluid and GC samples from 150 female patients undergoing intracytoplasmic sperm injection were collected in this study. The SCF concentrations in FFs and SCF messenger RNA (mRNA) in GCs were evaluated by using enzyme-linked immunosorbent assay and real-time polymerase chain reaction, respectively. The results showed that the levels of SCF protein and mRNA were significantly associated with oocyte maturation, normal fertilization, cleavage, and embryo quality. Moreover, the levels of SCF protein and mRNA in pregnancy group were also higher than those in the nonpregnancy group. The cutoff value of SCF in FF for predicting high-quality embryo was 1.346, with a sensitivity of 57.8% and a specificity of 72.4%, and the cutoff value of SCF in GCs for predicting high-quality embryo was 6.650, with a sensitivity of 64.4% and a specificity of 78.1%. In conclusion, our results showed a positive and statistically significant relationship between SCF level and oocyte maturation, normal fertilization, cleavage, embryo quality, and clinical pregnancy. Therefore, the levels of SCF in FF and GCs might be considered as a new marker for predicting oocyte developmental potential.

Stem cell factor in the serum of patients with esophageal cancer in relation to its histological types

IntroductionHematopoietic growth factors (HGFs), such as stem cell factor (SCF), may stimulate proliferation and differentiation of hematopoietic progenitor cells. Stem cell factor is also able to affect the growth of malignant tumors, including esophageal cancer (EC). The prognosis of EC patients’ survival is still unfavorable. Thus, novel biomarkers are necessary to improve the diagnosis and prognosis of EC patients. The aim of this study was to determine the serum SCF concentrations in EC patients in relation to its histological types and compare these levels with the classical tumor marker – carcinoembryonic antigen (CEA).Material and methodsThe study included 56 EC patients and 65 healthy controls. Serum SCF and CEA concentrations were measured using immunoenzyme assays. Moreover, diagnostic criteria of both proteins tested and the survival of EC patients were assessed.ResultsThe serum SCF concentrations were lower in EC patients compared to healthy controls, but the difference was not significant, whereas CEA levels were higher in EC patients than in healthy subjects. The serum SCF concentrations were significantly higher in patients with adenocarcinoma of the esophagus (AC) than in patients with esophageal squamous cell carcinoma (ESCC). Moreover, the diagnostic sensitivity of SCF (88%) was higher than for CEA (29%) and increased for combined analysis of SCF with CEA.ConclusionsOur findings suggest the potential role of serum SCF in the diagnosis of EC patients, especially in combination with the classical tumor marker. However, due to the non-specific nature of SCF, this issue requires further investigations performed on a larger population of EC patients.

The effect of stem cell factor on proliferation of human endometrial CD146+ cells

Stem cell factor (SCF) is a transcriptional factor which plays crucial roles in normal proliferation, differentiation and survival in a range of stem cells. The aim of the present study was to examine the proliferation effect of different concentrations of SCF on expansion of human endometrial CD146(+) cells. In this experimental study, total populations of isolated human endometrial suspensions after fourth passage were isolated by magnetic activated cell sorting (MACS) into CD146(+) cells. Human endometrial CD146(+) cells were karyotyped and tested for the effect of SCF on proliferation of CD146(+) cells, then different concentrations of 0, 12.5, 25, 50 and 100 ng/ml was carried out and mitogens-stimulated endometrial CD146(+) cells proliferation was assessed by MTT assay. Chromosomal analysis showed a normal metaphase spread and 46XX karyotype. The proliferation rate of endometrial CD146(+) cells in the presence of 0, 12.5, 25, 50 and 100 ng/ml SCF were 0.945±0.094, 0.962±0.151, 0.988±0.028, 1.679±0.012 and 1.129±0.145 respectively. There was a significant increase in stem/ stromal cell proliferation following in vitro treatment by 50 ng/ml than other concentrations of SCF (p=0.01). The present study suggests that SCF could have effect on the proliferation and cell survival of human endometrial CD146(+) cells and it has important implications for medical sciences and cell therapies.

Effect of roflumilast on airway remodelling in a murine model of chronic asthma.

Airway remodelling is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Roflumilast is a selective phosphodiesterase-4 inhibitor that has an anti-inflammatory effect in chronic obstructive pulmonary disease (COPD). The objective of this study was to study the effect of roflumilast on airway inflammation and remodelling in a murine model of chronic asthma. BALB/c mice sensitized to ovalbumin (OVA) were chronically exposed to intranasal OVA administration twice a week for additional 3months. Roflumilast was administered orally during the intranasal OVA challenge. A lung fibroblast cell line was used in the proliferation assay. Compared with control mice, mice chronically exposed to OVA developed eosinophilic airway inflammation, airway hyper-responsiveness (AHR), and exhibited features of airway remodelling. Administration of roflumilast significantly inhibited airway inflammation and AHR. Roflumilast also significantly decreased goblet cell hyperplasia and pulmonary fibrosis, which are parameters of airway remodelling. The levels of interleukin (IL)-4, IL-5, and IL-13 in the bronchoalveolar lavage (BAL) fluids were significantly lower in the roflumilast group. In vitro, roflumilast significantly inhibited stem cell factor (SCF)-induced cell proliferation of fibroblasts. The SCF concentration and mRNA expression in a murine model also significantly decreased with roflumilast treatment. These results suggest that the administration of roflumilast regulates airway inflammation, AHR, and airway remodelling in a model of chronic asthma. The beneficial effects from roflumilast may be related to the SCF/c-kit pathway.

Serum Stem Cell Factor Assay in Elderly Poor Responder Patients Undergoing IVF: A New Biomarker to Customize Follicle Aspiration Cycle by Cycle.

In humans, stem cell factor (SCF), produced during follicular phase, may reflect a successful stimulation and oocyte maturation and so it may be a predictor of in vitro fertilization (IVF) outcome. An observational cohort study was conducted on 37 poor responders scheduled for fresh nondonor IVF/intracytoplasmic sperm injection treatment with standard controlled ovarian stimulation (COS) using recombinant follicle-stimulating hormone (rFSH; S-COS group). A total of 35 women received a second treatment using both rFSH and recombinant luteinizing hormone (rLH; LH-COS group). From 144 samples collected at pickup day, serum concentration of SCF (s-SCF) and follicular levels of SCF (f-SCF) were measured by enzyme-linked immunosorbent assay (ELISA) kit. No differences were observed between the 2 protocols in terms of both f-SCF and s-SCF levels. The comparison between f-SCF and s-SCF levels showed a strong linear correlation. The comparison between s-SCF levels and clinical outcomes showed a statistically significant correlation between both the number of metaphase II (MII) oocytes retrieved and the embryos obtained after fertilization. Cases with at least 3 MII oocytes showed s-SCF values >800 pg/mL, 2 MII oocytes >600 pg/mL, and 1 MII oocytes >400 pg/mL. In 100% of cases with s-SCF <400 pg/mL, no MII oocytes were recovered. All 5 pregnancies occurred in patients with s-SCF values >1000 pg/mL. The introduction of s-SCF assay in the management of poor-responder patients may contribute to solving the dilemma of whether to cancel or proceed with the stimulation cycle.

Serum Concentration of Growth Factors in Dogs under Different Conditions of Distraction Osteogenesis.

Concentrations of insulin-like growth factors 1 and 2 (IGF-1 and IGF-2), stem cell factor (SCF), vascular endothelial growth factor (VEGF), and transforming growth factor β1 (TGF-β1) were measured in the blood serum of dogs subjected to experimental lengthening of shin bones. In animals subjected to shin bone lengthening at a rate of 1 mm/day in 4 steps, the concentrations of SCF and TGF-β1 significantly increased in the middle of distraction and IGF-1 concentration increased by the end of distraction. In animals subjected to lengthening at a rate of 1.5 mm/day in 6 steps, the levels of IGF-1 and TGF-β1 significantly increased in the middle of distraction and the concentration of IGF-2 at the end of distraction. In animals subjected to lengthening at a rate of 3 mm/day in 120 steps, the concentrations of IGF-1 and TGF-β1 significantly decreased in the middle of distraction and concentrations of IGF-1, VEGF, and TGF-β1 increased by the end of distraction.

Amh regulates SCF via the CAMP/PKA pathway in human granulosa cells

Anti-Mullerian hormone (AMH) and stem cell factor (SCF) are cytokines secreted by granulosa cells (GCs), playing different roles in ovarian physiology. We have demonstrated that recombinant human (rh)AMH inhibits the expression of SCF in cultured human (h)GCs. Little is known about the molecular mechanisms by which AMH regulates SCF. Here we investigated if there is a correlation between serum and follicular fluid (FF) AMH and SCF concentrations, and we evaluated if AMH has a regulatory effect on SCF at the transcription and translational levels.