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BackgroundStem/progenitor cells (SPCs) demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs) and their receptors in specific umbilical cord blood (UCB) SPC populations, including lineage-negative, CD34+, and CD133+ cells, with that in unsorted, nucleated cells (NCs).Methods and ResultsThe expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34+, and CD133+ cells). To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3) was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34+, and CD133+ cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34+ or CD133+ cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM) from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation.ConclusionsCollectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and that CM from SPCs favorable influence neural cell proliferation and survival. Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders.

Transplantation of genetically modified MSCs that produce neurotrophic growth factors may represent a useful strategy for treatment of different forms of retinopathies in the future.

Therapeutic options for amyotrophic lateral sclerosis (ALS) are still limited. Great hopes, however, are placed in growth factors that show neuroprotective abilities (e.g., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF)) and in the immune modulating features, in particular, the anti-inflammatory effects. In our study we aimed to investigate whether a bone marrow-derived lineage-negative (Lin-) cells population, after autologous application into cerebrospinal fluid (CSF), is able to produce noticeable concentrations of trophic factors and inflammatory-related proteins and thus influence the clinical course of ALS. To our knowledge, the evaluation of Lin- cells transplantation for ALS treatment has not been previously reported. Early hematopoietic Lin- cells were isolated from twelve ALS patients’ bone marrow, and later, the suspension of cells was administered into the subarachnoid space by lumbar puncture. Concentrations of selected proteins in the CSF and plasma were quantified by multiplex fluorescent bead-based immunoassays at different timepoints post-transplantation. We also chose microRNAs (miRNAs) related to muscle biology (miRNA-1, miRNA-133a, and miRNA-206) and angiogenesis and inflammation (miRNA-155 and miRNA-378) and tested, for the first time, their expression profiles in the CSF and plasma of ALS patients after Lin- cells transplantation. The injection of bone marrow cells resulted in decreased concentration of selected inflammatory proteins (C3) after Lin- cells injection, particularly in patients who had a better clinical outcome. Moreover, several analyzed miRNAs have changed expression levels in the CSF and plasma of ALS patients subsequent to Lin- cells administration. Interestingly, the expression of miR-206 increased in ALS patients, while miR-378 decreased both in the CSF and plasma one month after the cells’ injection. We propose that autologous lineage-negative early hematopoietic cells injected intrathecally may be a safe and feasible source of material for transplantations to the central nervous system (CNS) environment aimed at anti-inflammatory support provision for ALS adjuvant treatment strategies. Further research is needed to evaluate whether the observed effects could significantly influence the ALS progression.

IntroductionAdipose tissue is considered an endocrine organ and produces a number of biologically active substances.AimsTo consider the role that four adipokines – leptin, omentin-1, vaspin, and galectin-3 – play in the diagnosis of endometrium cancer and to investigate the association between serum concentrations of adipose tissue metabolism products and the diagnostics and prognosis in endometrial cancer.Patients and methodsThe study included 168 patients with body mass index (BMI) >20 kg/m2 admitted due to post-menopausal bleeding.ResultsA receiver operating characteristic curves test was performed to determine the diagnostic values of the proteins tested. For leptin and galectin-3 the area under the curve (AUC) values were 0.79/0.68, while for vaspin and omentin-1 the AUC values were 0.82/0.86 for all study patients. The final model identified the following independent risk factors: glucose concentration, BMI, waist circumference, leptin, and vaspin concentrations. Diagnostic values of leptin and galectin-3 with regard to differentiation between high (Fédération Internationale de Gynécologie Obstétrique [FIGO] III and IV) and low (FIGO I and II) stages of clinical tumor advancement and prediction of tumor grading (G1 vs G3) based on the AUC curve were 0.82/0.70 and 0.80/0.74. The AUC values for vaspin and omentin-1 with respect to differentiation between histopathological advancement and grading were 0.86/0.81 and 0.83/0.77, respectively. Significantly lower values of mean omentin-1 and vaspin concentrations were also demonstrated in cases of lymphatic vessel invasion, lymph node metastases, or deep endometrial infiltration (p=0.002, p=0.01, p=0.003, respectively).ConclusionIt appears that elevated concentrations of leptin, vaspin, and omentin-1 may indicate the presence of endometrial cancer. Furthermore, leptin serum level and vaspin appear to be useful tools in the assessment of clinical staging of endometrial cancer.

Abstract:In vitro studies have shown that amnion-produced growth factors participated in angiogenesis, re-epithelialization, and immunomodulation. The aim of our study was to investigate the growth factors and receptors produced by human amnion tissue and amniotic cells. Human amnions (hAM) were isolated, and amnion circles were dissected for in vitro analysis. Some amnion fragments were digested by the use of different methods to obtain two cell fractions, which were analysed for mesenchymal and epithelial cell markers. Amniotic circles and human amniotic cell fractions were cultured in a protein-free medium. Proteins secreted into the culture medium were analysed with a human growth factor antibody array. Conditioned culture media were added to human umbilical vein epithelial cells (HUVECs) to test for stimulation of migration (scratch test) and proliferation (Ki67 expression). Fraction 1 cells expressed both cytokeratin and mesenchymal cell markers which indicated that it was composed of a mixture of human amnion epithelial cells (hAECs) and mesenchymal stromal cells (hAMSCs). Fraction 2 cells mainly expressed cytokeratin and, therefore, were designed as hAECs. Secretion of proteins by the cultured cells increased with time. The hAM cultures secreted EGF-R, IGF, and IGFBP-2, -3 and -6; Cell Fraction 1 secreted NT-4, whereas Cell Fraction 2 secreted G-CSF, M-CSF, and PDGF. Conditioned media of hAM cultures stimulated HUVECs migration. We have showed for the first time that human amnions and amniotic cells secreted IGFBP-6, MCSF-R, PDGF-AB, FGF-6, IGFBP-4, NT-4, and VEGF-R3. We found that Cell Fraction 1, Cell Fraction 2, and the whole amnion secreted different proteins, possibly due to different proportions of amnion-derived cells and different cell-cell interactions. The hAM cell factors remained functional in vitro and induced intensified migration of HUVECs. The growth factors and receptors found in amnion or amniotic cell media might be used for regenerative medicine.

BackgroundMMP and TIMP play an important role in the degradation of extracellular matrix components which are essential for tumor growth, invasion and metastasis. Aim of this research was to assess MMP3 and TIMP3 as prognostic factors among patients with ovarian cancer.ResultsIt was found that high levels of output MMP3 correlated with shortened overall survival time of patients by 9.7 months. In addition, it has been shown that high concentrations of output MMP3 were significantly associated with a shorter disease free time in median concentrations implemented p = 0.0059. Statistically significant dependence has been shown between an average concentration of TIMP3 protein to the overall survival of patients. The higher output concentration of TIMP3, the longer patients’ survival by 8.9 month. In addition, it was found that high TIMP3 concentrations output were associated with a significantly longer disease free duration at a median concentrations p = 0.007.ConclusionPreliminary research shows that output levels of MMP3 and TIMP3 proteins correlate with overall survival of patients. In some cases also time free of illness.

Obesity is a well-known factor that leads to many diseases including endometrial cancer. The adipose tissue is a heterogeneous organ of internal secretion. Visfatin is a newly discovered protein produced by fat tissues. The purpose of this work was to evaluate serum level concentrations of visfatin in patients with endometrial cancer based on clinical progression and histopathological tumor differentiation. The diagnostic capabilities of visfatin protein in high differentiation (FIGO III and IV) from a lower (FIGO I and II) clinical stage and prognostic degree of cell differentiation (G1 versus G2, G2 versus G3) on the basis of the analysis of the area under the ROC curve are as follows: 0.87, 0.81, and 0.86. Significantly higher concentrations of visfatin have been observed in patients with invasion of the blood vessels (p = 0.02) and lymph node metastases (p = 0.01) in reference to the depth of infiltration of the endometrium (p = 0.004), as well as the size of the tumor (p = 0.003). Visfatin serum concentrations did not differ due to the invasion of the lymphatic vessels only. Visfatin seems to be a good marker of endometrial cancer progress. High visfatin serum level predicts poor prognosis in endometrial cancer patients.