From Primary MSC Culture of Adipose Tissue to Immortalized Cell Line Producing Cytokines for Potential Use in Regenerative Medicine Therapy or Immunotherapy.

For twenty-five years, attempts have been made to use MSCs in the treatment of various diseases due to their regenerative and immunomodulatory properties. However, the results are not satisfactory. Assuming that MSCs can be replaced in some therapies by the active factors they produce, the immortalized MSCs line was established from human adipose tissue (HATMSC1) to produce conditioned media and test its regenerative potential in vitro in terms of possible clinical application.

Activity of the human immortalized endothelial progenitor cell line HEPC-CB.1 supporting in vitro angiogenesis.

The human HEPC-CB.1 cell line with many characteristics of endothelial progenitor cells (EPC) was tested for its proangiogenic properties as a potentially therapeutic compound. HEPC-CB.

Autotransplantation of the Adipose Tissue-Derived Mesenchymal Stromal Cells in Therapy of Venous Stasis Ulcers.

Adipose tissue is a reliable source of mesenchymal stromal cells (MSC) for use in regenerative medicine. The aim of this pilot study was to describe the method, and assess the safety and the potential efficacy of transplantation of autologous adipose tissue-derived MSC for the treatment of chronic venous stasis ulcers. Study group consisted of 11 patients (mean age: 66.

MRP1 protein expression in leukemic stem cells as a negative prognostic marker in acute myeloid leukemia patients.

Background: It is well established that expression of multi-drug resistance (MDR) proteins (MDR1, BCRP, MDR3, MRP1, and LRP) in leukemic blasts correlates with acute myeloid leukemia (AML) patients' clinical response. Assuming that leukemic stem cells (LSC) are resistant to chemotherapy and responsible for relapse, it might be clinically relevant to evaluate the expression level of MDR proteins in LSC and relate it to the clinical outcome.

Methods: Bone marrow samples from 26 patients with de novo AML were labeled with antibodies to distinguish CD34+CD38-CD123+ LSC population and with antibodies against MDR1, BCRP, MDR3, MRP1, or LRP proteins.

Increased Endothelial Progenitor Cell Number in Early Stage of Endometrial Cancer.

Objectives: It is generally believed that circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) reflect the state of the endothelium, its injury and/or repair possibilities. In different types of cancers, increased numbers of CECs and EPCs were found, suggesting their participation in cancer angiogenesis. The objective of this study was to determine whether, in the blood circulation of women with early endometrial cancer, CEC and EPC levels differ from those of healthy women of similar age.

Expression and activity of multidrug resistance proteins in mature endothelial cells and their precursors: A challenging correlation.

Active cellular transporters of harmful agents-multidrug resistance (mdr) proteins-are present in tumor, stem and endothelial cells, among others. While mdr proteins are broadly studied in tumor cells, their role in non-tumor cells and the significance of their action not connected with removal of harmful xenobiotics is less extensively documented. Proper assessment of mdr proteins expression is difficult.

Euphorbia Species-derived Diterpenes and Coumarins as Multidrug Resistance Modulators in Human Colon Carcinoma Cells.

Background: Recently, many new potent multidrug resistance (MDR) reversal agents have been discovered, among them lathyrane and jatrophane diterpenes isolated from various Euphorbia species. In the present study, the cytotoxicity, P-glycoprotein inhibition activity, and MDR reversal potency of six diterpenes and two coumarins from two Euphorbia species were studied in human colon carcinoma LoVo cells, and doxorubicin-resistant, LoVo/Dx cells.

Materials And Methods: Cytotoxicity of the studied compounds (alone and in combination with doxorubicin) was investigated.

Temporary elimination of IL-10 enhanced the effectiveness of cyclophosphamide and BMDC-based therapy by decrease of the suppressor activity of MDSCs and activation of antitumour immune response.

The antitumour activity of the dendritic cell (DC)-based cellular vaccines is greatly reduced in hostile tumour microenvironment. Therefore, there are many attempts to eliminate or neutralize both suppressor cells and cytokines. The aim of the investigation was to verify if temporary elimination of IL-10 just before injection of bone marrow-derived DCs (BMDCs) enhance the antitumour activity of applied vaccines and help to overcome the immunosuppressive tumour barrier.

Cyclophosphamide and IL-12-transduced DCs enhance the antitumor activity of tumor antigen-stimulated DCs and reduce Tregs and MDSCs number.

A hostile tumor microenvironment, characterized by an abundance of T regulatory cells and myeloid-derived suppressor cells (MDSCs), considerably limits the efficacy of dendritic cell (DC)-based vaccines. The intention of this study was to enhance the antitumor activity of vaccines consisting of bone marrow-derived DCs stimulated with TAg (BMDC/TAg) via single administration of cyclophosphamide and multiple injections of interleukin (IL)-12-transduced DCs (BMDC/IL-12). The combined chemoimmunotherapy was applied in the treatment of mice with subcutaneously (SC) growing, advanced MC38 colon carcinoma.

Pregnancy-induced hypertension is accompanied by decreased number of circulating endothelial cells and circulating endothelial progenitor cells.

Maternal endothelial dysfunction is one of the main features of pregnancy-induced hypertension (PIH). It is generally accepted that circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) reflect the state of the endothelium, its injury and/or repair possibilities. The objective of this study was to determine whether the CECs and EPCs numbers in the circulation of women with PIH reflect the presence of this pathology.

Prognostic value of the Fas/Fas ligand system in breast cancer.

Fas and its ligand (FasL) are known to play a crucial role in the genetically controlled mechanism of cell death, and their deregulation in cancer cells is involved in the immune escape of the tumor. The aim of this review is to analyze the current knowledge on the prognostic value of Fas/FasL in breast cancer patients. Both the results of other authors and our own experiences indicate that the lack of Fas ligand, and particularly Fas, is related to a significantly worse prognosis.

[Natural killer cells complot with dendritic cells].

Dendritic cells (DC) were initially considered as antigen presenting cells participating in the polarization of the immune response. Further understanding of their biology allowed determining their additional functions such as immunoregulatory and cytotoxicity. Until recently natural killer (NK) cells were known as a homogeneous population of lymphocytes capable of non-specific recognizing and eliminating target cells.

Multidrug resistance reversal and apoptosis induction in human colon cancer cells by some flavonoids present in citrus plants.

Multidrug resistance (MDR) of cancer cells constitutes one of the main reasons for chemotherapy failure. The search for nontoxic modulators that reduce MDR is a task of great importance. An ability to enhance apoptosis of resistant cells would also be beneficial.

Antitumor effect of murine dendritic and tumor cells transduced with IL-2 gene.

Interleukin (IL-) 2 acts on a number of types of immune cells promoting their effector functions. To replace systemic administration of recombinant form of this cytokine, various genetically modified cells have been used indifferent preclinical models for tumor growth inhibition. In this study, dendritic or tumor cells transduced with retroviral vector carrying IL-2 gene (JAWS II/IL-2, X63/IL-2, MC38/IL-2 cells) alone or combined with tumor antigen-stimulated dendritic cells (JAWS II/TAg) were exploited to treat colon carcinoma MC38-bearing mice.

Reduced number of circulating endothelial progenitor cells (CD133+/KDR+) in patients with plaque psoriasis.

Background: Psoriasis is associated with an increased cardiovascular risk. Circulating endothelial progenitor cells (CEPCs) play a significant role in the maintenance of vascular homeostasis.

Objective: The aim of this study was to evaluate the number of CEPCs in patients with psoriasis compared to controls and assess possible correlations between the number of these cells and the plasma levels of vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and clinical features of psoriasis.

Increased number of circulating endothelial cells (CECs) in patients with psoriasis--preliminary report.

Background: Numerous studies have demonstrated increased cardiovascular risk in psoriasis. Circulating endothelial cells (CECs) have been proposed as a new marker of endothelial dysfunction that plays an important role in pathogenesis of atherosclerosis.

Objective: The aim of this study was to compare the number of CECs in psoriatic patients to a control group and to analyze possible correlations between the numbers of CECs and the plasma levels of classical markers of endothelial dysfunction, such as: sICAM-1, sE-selectin and von Willebrand factor (vWF).

Endostatin and vascular endothelial growth factor: potential regulators of endothelial progenitor cell number in chronic kidney disease.

Introduction: Cardiovascular mortality is significantly increased in patients with chronic kidney disease (CKD). The number of circulating endothelial progenitor cells (EPCs) may affect vascular regenerative potential and thus influence cardiovascular mortality.

Objectives: The aim of the study was to assess the number of circulating EPCs and the factors that potentially affect these cells, including vascular endothelial growth factor (VEGF) and endostatin, in patients with CKD.

CD133 positive progenitor endothelial cell lines from human cord blood.

Endothelial progenitor cells (EPCs) modulate postnatal vascularization and contribute to vessel regeneration in adults. Stem cells and progenitor cells were found in umbilical cord blood, bone marrow, and mobilized peripheral blood cells, from where they were isolated and cultured. However, the yield of progenitor cells is usually not sufficient for clinical application and the quality of progenitor cells varies.

Generation of antitumor response by IL-2-transduced JAWS II dendritic cells.

Antigen-loaded dendritic cells (DCs) are a promising tool for inducing a tumor-specific immune response. It seems probable that co-administration of those cells together with cytokine-transduced DCs can further increase effectiveness of the antitumor vaccine. The local production of IL-2 by genetically modified DCs may result in alteration of the unfavorable tumor environment causing immune response dysfunction.

Stilbenes as multidrug resistance modulators and apoptosis inducers in human adenocarcinoma cells.

Background: The search for promising modulators of cancer multidrug resistance (MDR) that are able to reduce the activity of P-glycoprotein, thus restoring the cytotoxicity of anticancer drugs, is ongoing. The identification of compounds that overcome the apoptosis deficiency that frequently accompanies MDR is also of great therapeutic importance.

Materials And Methods: Four stilbenes, resveratrol, piceatannol and its two derivatives, were tested for their MDR-modulating and apoptosis-inducing activity in drug-sensitive (LoVo) and doxorubicin-resistant human adenocarcinoma cell line (LoVo/Dx) by means of flow cytometry and fluorescence microscopy.

8-Prenylnaringenin is an inhibitor of multidrug resistance-associated transporters, P-glycoprotein and MRP1.

Flavonoids with hydrophobic e.g. prenyl substituents might constitute the promising candidates for multidrug resistance (MDR) reversal agents.

The anti-angiogenic activity of IL-12 is increased in iNOS-/- mice and involves NK cells.

We have previously reported that the in vivo transfer of murine interleukin-12 (IL-12) gene using a Semliki Forest virus vector induced tumor regression through inhibition of tumor blood vessel formation. To examine whether IL-12 anti-angiogenic activity interferes with the NO pathway, we used inducible nitric oxide synthase-deficient mice (iNOS-/-) and demonstrated that the anti-tumor effect of IL-12 is more pronounced in these mice. In addition, despite the increased level of intratumoral VEGF in iNOS-/- mice, IL-12 induced a stronger inhibition of blood vessel formation.

Tumour antigen-loaded mouse dendritic cells maturing in the presence of inflammatory cytokines are potent activators of immune response in vitro but not in vivo.

The use of dendritic cells (DCs) loaded with tumour antigen is one of the most promising approaches to induce tumour-specific immune response. However, methods of the vaccine preparation have not yet been standardized. The purpose of the study was to analyse the anti-tumour efficacy of tumour antigen-loaded mouse bone marrow-derived dendritic cells (BM-DC/TAg) at different maturation stages.

Lectins from the Red Marine Algal Species Bryothamnion seaforthii and Bryothamnion triquetrum as Tools to Differentiate Human Colon Carcinoma Cells.

The carbohydrate-binding activity of the algal lectins from the closely related red marine algal species Bryothamnion triquetrum (BTL) and Bryothamnion seaforthii (BSL) was used to differentiate human colon carcinoma cell variants with respect to their cell membrane glyco-receptors. These lectins interacted with the cells tested in a dose-dependent manner. Moreover, the fluorescence spectra of both lectins clearly differentiated the cells used as shown by FACS profiles.