Chemokine Homeostasis in Healthy Volunteers and during Pancreatic and Colorectal Tumor Growth in Murine Models.

Chemokines are involved in the humoral regulation of body homeostasis. Changes in the blood level of chemokines were found in cancer, atherosclerosis, diabetes, and other systemic diseases. It is essential to distinguish the effects of co-morbid pathologies and cancer on the level of chemokines in the blood.

Asymmetric depth-filtration: A versatile and scalable method for high-yield isolation of extracellular vesicles with low contamination.

We developed a novel asymmetric depth filtration (DF) approach to isolate extracellular vesicles (EVs) from biological fluids that outperforms ultracentrifugation and size-exclusion chromatography in purity and yield of isolated EVs. By these metrics, a single-step DF matches or exceeds the performance of multistep protocols with dedicated purification procedures in the isolation of plasma EVs. We demonstrate the selective transit and capture of biological nanoparticles in asymmetric pores by size and elasticity, low surface binding to the filtration medium, and the ability to cleanse EVs held by the filter before their recovery with the reversed flow all contribute to the achieved purity and yield of preparations.

Silicon-Gold Nanoparticles Affect Wharton's Jelly Phenotype and Secretome during Tri-Lineage Differentiation.

Multiple studies have demonstrated that various nanoparticles (NPs) stimulate osteogenic differentiation of mesenchymal stem cells (MSCs) and inhibit adipogenic ones. The mechanisms of these effects are not determined. The aim of this paper was to estimate Wharton's Jelly MSCs phenotype and humoral factor production during tri-lineage differentiation per se and in the presence of silicon-gold NPs.

Mesenchymal Stromal Cells Isolated from Ectopic but Not Eutopic Endometrium Display Pronounced Immunomodulatory Activity In Vitro.

A comparative analysis of the cell surface markers and immunological properties of cell cultures originating from normal endometrium and endometrioid heterotopias of women with extragenital endometriosis was carried out. Both types of cell cultures expressed surface molecules typical of mesenchymal stromal cells and did not express hematopoietic and epithelial markers. Despite similar phenotype, the mesenchymal stromal cells derived from the two sources had different immunomodulation capacities: the cells of endometrioid heterotopias but not eutopic endometrium could suppress dendritic cell differentiation from monocytes as well as lymphocyte proliferation in allogeneic co-cultures.

Effect of Intranasal Administration of Multipotent Mesenchymal Stromal Cell Exosomes on Memory of Mice in Alzheimer's Disease Model.

We studied the effect of intranasal administration of exosomes obtained by culturing of multipotent mesenchymal stromal cells (MMSC) isolated from the Wharton's jelly of the human umbilical cord on spatial memory of olfactory bulbectomized mice demonstrating the basic signs of a sporadic form of Alzheimer's disease. Intranasal administration of isolated exosomes expressing typical markers CD9, CD63 and CD81 improved spatial memory in bulbectomized animals, which manifested in a significant increase in the number of visits to the target sector and the time spent there in comparison with indifferent sectors. After administration, labeled exosomes were found in the hippocampus and neocortex, the structures playing an important role in learning and memory processes and affected by Alzheimer's disease.

Effect of Transplantation of Neural Stem and Progenitor Cells on Memory in Animals with Alzheimer's Type Neurodegeneration.

The effects of systemic and intracerebral transplantation of human fetal neural stem and progenitor cells were studied on the model of olfactory bulbectomy in mice with developing signs of sporadic Alzheimer's disease. It was found that transplantation of these cells at certain stages of disease development contributed to improvement of spatial memory and preservation of hippocampal neurons in these animals.

Neuroregeneration: Regulation in Neurodegenerative Diseases and Aging.

It had been commonly believed for a long time, that once established, degeneration of the central nervous system (CNS) is irreparable, and that adult person merely cannot restore dead or injured neurons. The existence of stem cells (SCs) in the mature brain, an organ with minimal regenerative ability, had been ignored for many years. Currently accepted that specific structures of the adult brain contain neural SCs (NSCs) that can self-renew and generate terminally differentiated brain cells, including neurons and glia.

Myths, reality and future of mesenchymal stem cell therapy.

Mesenchymal stem cell (MSC) therapy represents an alternative approach for tissue regeneration and inflammation control. In spite of a huge amount of preclinical data that has been accumulated on the therapeutic properties of MSCs, there are many conflicting results, possibly due to differences in the properties of MSCs obtained from different sources or underestimated mechanisms of MSC in vivo behavior. This review consolidates the in vivo effects of MSC therapy, discusses the fate of MSCs after intravascular and local delivery and proposes possible trends in MSC therapy.

Ultrastructural and Immunohistochemical Features of Telocytes in Placental Villi in Preeclampsia.

A new cell type, interstitial Cajal-like cell (ICLC), was recently described in different organs. The name was recently changed to telocytes (TCs), and their typical thin, long processes have been named telopodes (Tp). TCs regulate the contractile activity of smooth muscle cells and play a role in regulating vessel contractions.

Neural stem/progenitor cells maintained under different culture conditions alter differentiation capacity of monocytes to generate dendritic cells.

Cell therapy of the nervous system disorders using neural stem/progenitor cells (NSPCs) proved its efficacy in preclinical and pilot clinical studies. The mechanisms of the beneficial effects of NSPCs transplantation include replacement of damaged cells, paracrine activation of the regeneration, and immunomodulation. Detailed assessment of NSPCs-induced immunomodulation can contribute to better control of autoimmune reactions and inflammation in patients with neurodegenerative diseases.

Activation of NK Cells in Mixed Cultures of Wharton's Jelly Mesenchymal Stromal Cells and Peripheral Blood Lymphocytes.

Mesenchymal stromal cells possess immunosuppressive properties that might be used for the therapy of inflammatory diseases of various geneses. The effects of mesenchymal stromal cells depend on their lifetime in the recipient tissues. During heterologous transplantation, mesenchymal stromal cells are eliminated by NK cells.

[Morphological Features of Mesenhymal Stroma Cells of Chorionic Villi].

Background: Nowadays autologous mesenchymal placental stromal cells (MSCs) may use to treat for various diseases both of the mother and the child. Stroma of the placenta villi is appropriated origin for cell culture isolation.

Aim: of the study was to evaluate the possibility for selection and use of placental tissue for mesenchymal stromal cells.

Characteristics of Trophoblasts in Long-Term Culture.

We analyzed more than 40 cytotrophoblast cultures derived from cell islets that grew from trypsinized tissue fragments of placental microvilli. Phenotypic variability of trophoblasts was demonstrated. Changes in trophoblast morphology from epithelium-like or oval cells to bipolar and spindle-shaped or twisted and then to mesenchymal-like cells as well as intensive expression of cytokeratin-7 and vimentin attested to epithelial-mesenchymal transition of trophoblasts during in vitro culturing.

Proliferation of Peripheral Blood Lymphocytes and Mesenchymal Stromal Cells Derived from Wharton's Jelly in Mixed and Membrane-Separated Cultures.

We studied the effect of mesenchymal stromal cells on proliferation of CFSE-stained T cells in mixed and membrane-separated (Transwell) cultures and in 3D culture of mesenchymal stromal cells from Wharton's jelly. The interaction of mesenchymal stromal cells with mitogen-activated peripheral blood lymphocytes from an allogeneic donor was followed by suppression of T-cell proliferation in a wide range of cell proportions. Culturing in the Transwell system showed the absence of suppression assessed by the fraction of proliferating cells and by the cell cycle analysis.

Isolation and characterization of trophoblasts from enzymatic explants of human term placenta.

In the present study, we describe a new method of isolation and culture of human villous and extravillous trophoblasts from term placenta. The cultivation of trypsinized placental villous tissue explants, followed by the isolation of cells from outgrowth islets allows for obtaining a cytotrophoblast subpopulation that is free from contamination by other cell types. Compared to other methods, our protocol is mild, simple and effective, does not request costly reagents and provides isolation of the mononuclear cytotrophoblast cell populations free from contamination by other types of placental cells.

Cytokine Production in Mixed Cultures of Mesenchymal Stromal Cells from Wharton's Jelly and Peripheral Blood Lymphocytes.

We compared the production of 19 humoral factors in mixed cultures of mesenchymal stromal cells from Wharton's jelly and allogenic peripheral blood lymphocytes. For evaluation of the specificity of immunosuppressive activity of mesenchymal stromal cells, comparative analysis of the production of these humoral factors in mixed cultures of lymphocytes and epithelial BxPC-3 cells was conducted. The production of soluble factors in both mono- and mixed cultures significantly correlated (p<0.

Lutein and its oxidized forms in eye structures throughout prenatal human development.

The presence of carotenoids in the vitreous body, retina, lens, retinal pigment epithelium together with choroid (hereinafter RPE), and ciliary body and iris together with choroidal stroma (hereinafter CBI) was studied throughout the second trimester of prenatal development of the human eye. It has been found that the vitreous body, retina, and RPE contain lutein and its oxidized forms. Zeaxanthin was not found in the tissues studied.

Ultrastructural Characteristics of Placental Telocytes.

Telocytes of placental villi were studied by electronic microscopy during physiological pregnancy. Ultrastructural features of telocytes indicating their heterogeneity and presence of at least three types of villi depending on their localization and kind were observed. All placental telocytes were characterized by small amount of organelles including mitochondria.

Albumin in the Vitreous Body, Retina and Lens of Human Fetal Eye.

The content of serum albumin was evaluated in the vitreous body, retina, and lens of human fetuses of 14, 16, 17, 18 and 24 weeks of gestation. Albumin was detected in these tissues. PCR analysis revealed no albumin mRNA in the retina or in the lens, while in fetal liver (control) mRNA for this protein was expressed.

Conditions for Collection of Placental Tissue Samples for Culturing of Multipotent Mesenchymal Stromal Cells.

Placentas from women aged 25-32 years with normal course of gestation were studied. It is essential to stick to certain methodological approaches for preparing viable multipotent mesenchymal stromal cell culture and to carry out morphological (macro and micro) evaluation of the chorionic villi, umbilical cords, and placentas. At stage I of the study, patients' histories, labor course, and examinations of the newborns should be analyzed to exclude women with genital and extragenital diseases.

Interaction of Lymphocytes with Mesenchymal Stem Cells.

We studied the interaction of neural stem cells and dental pulp-derived mesenchymal stem cells with lymphocytes from autologous and heterologous donors. Flow cytometry analysis with the use of CFSE-labeled lymphocytes demonstrated an increase in the content of proliferating CD8, CD16 and CD56 cells, but not CD4 cells in cultures of HLA-DR-negative mesenchymal stromal cells from the dental pulp co-cultured with lymphocytes. In neural cultures expressing HLA-DR, all subpopulations of T cells and NK cells were activated.

Antiproliferative Effects of Mesenchymal Stem Cells and Epithelial Cells on Lymphocytes.

We analyzed the interactions between peripheral blood lymphocytes from heterologous donors with mesenchymal stem cells obtained from the tooth pulp and trophoblast. In mixed cultures, proliferation of both lymphocytes and mesenchymal stem cells was suppressed. Similar suppressive effects were observed in lymphocyte cultures mixed with epithelial cells (hepatocytes HeG2 and renal epithelial cells HEK293).

Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro.

Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity.

Updates on the Production of Therapeutic Antibodies Using Human Hybridoma Technique.

Therapeutic antibodies are implicated into the very promising and fast growing area of pharmaceutics. Human hybridoma technology, allowing generation of natural human antibodies in a native form, seems to be the most direct way that require no additional modifications for production of therapeutic antibodies. However, technical difficulties in human hybridoma creation discovered in the 80s of the last century have switched the mainstream therapeutic antibody development into new directions like display and transgenic mice techniques.