Mesenchymal stem cells (MSCs) are a source of a wide range of soluble factors, including different proteins, growth factors, cytokines, chemokines, and DNA and RNA molecules, in addition to numerous secondary metabolites and byproducts of their metabolism. MSC secretome can be formally divided into secretory and vesicular parts, both of which are very important for intercellular communication and are involved in processes such as angiogenesis, proliferation, and immunomodulation. Exosomes are thought to have the same content and function as the MSCs from which they are derived, but they also have a number of advantages over stem cells, including low immunogenicity, unaltered functional activity during freezing and thawing, and a lack of tumor formation. In addition, MSC pre-treatment with various inflammatory factors or hypoxia can alter their secretomes so that it can be modified into a more effective treatment. Paracrine factors secreted by MSCs improve the survival of other cell populations by several mechanisms, including immunomodulatory (mostly anti-inflammatory) activity and anti-apoptotic activity partly based on Hsp27 upregulation. Reproductive medicine is one of the fields in which this cell-free approach has been extensively researched. This review presents the possible applications and challenges of using MSC secretome in the treatment of infertility. MSCs and their secretions have been shown to have beneficial effects in various models of female and male infertility resulting from toxic damage, endocrine disorders, trauma, infectious agents, and autoimmune origin.

This study describes the effect of collagen type I (Col I) oxidation on its physiological remodeling by adipose tissue-derived mesenchymal stem cells (ADMSCs), both mechanical and proteolytic, as an in vitro model for the acute oxidative stress that may occur in vivo upon distinct environmental changes. Morphologically, remodeling was interpreted as the mechanical rearrangement of adsorbed FITC-labelled Col I into a fibril-like pattern. This process was strongly abrogated in cells cultured on oxidized Col I albeit without visible changes in cell morphology. Proteolytic activity was quantified utilizing fluorescence de-quenching (FRET effect). The presence of ADMSCs caused a significant increase in native FITC-Col I fluorescence, which was almost absent in the oxidized samples. Parallel studies in a cell-free system confirmed the enzymatic de-quenching of native FITC-Col I by Clostridial collagenase with statistically significant inhibition occurring in the oxidized samples. Structural changes to the oxidized Col I were further studied by differential scanning calorimetry. In the oxidized samples, an additional endotherm with sustained enthalpy (∆H) was observed at 33.6 °C along with Col I’s typical one at 40.5 °C. Collectively, these data support that the remodeling of Col I by ADMSCs is altered upon oxidation due to intrinsic changes to the protein’s structure, which represents a novel mechanism for the control of stem cell behavior.

The aim of our study was to determine the type and frequency of chromosomal aberrations and polymorphisms in men with different degrees of spermatogenic failure in comparison to men with normozoospermia, in order to find correlations between cytogenetic findings and the abnormal results of semen analysis. In our study, we performed cytogenetic analysis in 901 infertile men, divided into five groups according to semen analysis—normozoospermia (86), asthenozoospermia (394), oligoasthenozoospermia (182), severe male factor (100), and azoospermia (139). The frequency of polymorphisms was similar in all groups (11–16%, without significant differences). The frequency of numerical and structural aberrations increases with the degree of the spermatogenic failure (3.5% in normozoospermia, 5.6% in asthenozoospermia, 9.8% in oligoasthenozoospermia, 9% in severe male factor, and 13.5% in azoospermia). We found a significantly higher incidence of numerical chromosomal aberrations in severe male factor (7%) and azoospermia (9.3%). Oligoasthenozoospermia occured in 45% of cases with translocation, compared to 20% in the group with a normal karyotype. We revealed that chromosomal translocations are tightly associated with oligoasthenozoospermia, whereas numerical chromosomal aberrations—with severe male factor and azoospermia. The impact of chromosome polymorphisms on male infertility should be studied in greater detail.

Objective(s): Mesenchymal stem cells (MSCs) exist in almost all tissues. Their unique nature is completed by their immunomodulatory functions, holding promise for the treatment of many diseases. An inflammatory environment precedes the immunosuppressive abilities of MSCs and this study was intended to better understand how umbilical cord MSCs (UCMSCs) react to the process of inflammation, regarding their basic characteristics and behavior when primed with the key pro-inflammatory cytokine, Interferon-gamma (IFN gamma). Materials and Methods: Human MSCs from the umbilical cord were isolated, expanded, and treated with IFN gamma. Primed cells were analyzed to define their ability to form colonies, their morphology, differentiation potential, proliferation, and apoptosis rate. Results: UCMSCs treated with IFN gamma changed their fibroblast-like morphology and retained the expression of typical MSCs markers. IFN gamma treated UCMSCs had significantly higher MFI levels regarding the expression of HLA-I (980.43 +/- 556.64) and PD-L1 (598.04 +/- 416.90) compared with the control cells (144.97 +/- 78.5 and 122.05 +/- 103.83, respectively; P<0.01). Under the influence of IFN gamma, the cells had a lower population doubling time compared with the control cultures (50.345 +/- 9.155 versus 61.135 +/- 21.110, respectively; P<0.01) and higher numbers of colony-forming unit-fibroblasts (26.0 +/- 12.2 versus 10.2 +/- 8.0, respectively; P<0.05). The primed MSCs could not undergo osteogenic and adipogenic differentiation. IFN gamma increased the percentage of cells in the apoptotic state on day eight (29.470 +/- 6.59 versus 15.708 +/- 6.190, respectively; P<0.01). Conclusion: The properties of UCMSCs can be influenced by the pro-inflammatory cytokine IFN gamma.

Autoimmune diseases represent a severe personal and healthcare problem that seeks novel therapeutic solutions. Mesenchymal stem cells (MSCs) are multipotent cells with interesting cell biology and promising therapeutic potential. The immunoregulatory effects of secretory factors produced by umbilical cord mesenchymal stem cells (UC-MSCs) were assessed on B lymphocytes from 17 patients with systemic lupus erythematosus (SLE), as defined by the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, and 10 healthy volunteers (HVs). Peripheral blood mononuclear cells (PBMCs) from patients and HVs were cultured in a UC-MSC-conditioned medium (UC-MSCcm) and a control medium. Flow cytometry was used to detect the surface expression of CD80, CD86, BR3, CD40, PD-1, and HLA-DR on CD19+ B cells and assess the percentage of B cells in early and late apoptosis. An enzyme-linked immunosorbent assay (ELISA) quantified the production of BAFF, IDO, and PGE2 in PBMCs and UC-MSCs. Under UC-MSCcm influence, the percentage and mean fluorescence intensity (MFI) of CD19+BR3+ cells were reduced in both SLE patients and HVs. Regarding the effects of the MSC secretome on B cells in lupus patients, we observed a decrease in CD40 MFI and a reduced percentage of CD19+PD-1+ and CD19+HLA-DR+ cells. In contrast, in the B cells of healthy participants, we found an increased percentage of CD19+CD80+ cells and decreased CD80 MFI, along with a decrease in CD40 MFI and the percentage of CD19+PD-1+ cells. The UC-MSCcm had a minimal effect on B-cell apoptosis. The incubation of patients’ PBMCs with the UC-MSCcm increased PGE2 levels compared to the control medium. This study provides new insights into the impact of the MSC secretome on the key molecules involved in B-cell activation and antigen presentation and survival, potentially guiding the development of future SLE treatments.