Cells in the umbilical cord stroma have gained attention in recent years; however, differentiation to certain lineages in humans has been demonstrated in few studies. Unlike bone marrow MSCs, human umbilical cord stroma cells (HUCSCs) are far from being well characterized. This study attempts to describe proliferation, structural, and differentiation properties of these cells to account for their exceptional nature in many aspects. Cellular dynamics, cellular structure, and the degree of transformations during expansion and differentiation into mesenchymal and neuronal lineages were examined in vitro over a 10-month period. Comparisons with human bone marrow MSCs regarding differentiation were performed. HUCSCs in culture revealed two distinct cell populations, type 1 and type 2 cells, that possessed differential vimentin and cytokeratin filaments. Corresponding cells were encountered in cord sections displaying region-specific localization. α-Smooth muscle actin and desmin filaments, which were evident in cord sections, diminished through passages. No difference was noted regarding type 1 and type 2 cells in differentiation to chondrogenic, adipogenic, and osteogenic lineages, whereas a preferential differentiation was noted in neuronal lineage. Relative success was achieved by production of chondrocytic spheres and osteogenic monolayers, whereas adipocytes were immature compared with bone marrow MSCs. The presence of neuronal markers suggests that they transform into a certain state of maturity under neurogenic induction. Conclusively, HUCSCs retain their original phenotype in culture without spontaneous differentiation, have a limited lifespan, and bear multipotent stem cell characteristics. Given these characteristics, they may be generally considered progenitor cells if manipulated under appropriate conditions and deserve further study to be potentially used in cell-based therapies.

Human umbilical cord (UC) has been a tissue of increasing interest in recent years. Many groups have shown the stem cell potency of stromal cells isolated from the human UC mesenchymal tissue, namely, Wharton's jelly. Since UC is a postnatal organ discarded after birth, the collection of cells does not require an invasive procedure with ethical concerns. Stromal cells, as the dominant cells of this fetus-derived tissue, possess multipotent properties between embryonic stem cells and adult stem cells. They bear a relatively higher proliferation rate and self-renewal capacity. Although they share common surface markers with bone marrow-derived MSCs, they also express certain embryonic stem cell markers, albeit in low levels. Without any spontaneous differentiation, they can be successfully differentiated into mature adipocytes, osteoblasts, chondrocytes, skeletal myocytes, cardiomyocytes, neurons, and endothelial cells. While causing no immunorejection reaction, they effectively function in vivo as dopaminergic neurons, myocytes, and endothelial cells. Given these characteristics, particularly the plasticity and developmental flexibility, UC stromal cells are now considered an alternative source of stem cells and deserve to be examined in long-term clinical trials. This review first aims to document the published findings so far regarding the nature of human UC stroma with special emphasis on the spatial distribution and functional structure of stromal cells and matrix, which serves as a niche for residing cells, and, secondly, to assess the in vitro and in vivo experiments in which differential stem cell potencies were evaluated.Disclosure of potential conflicts of interest is found at the end of this article.

Bisphenol-A (BPA) is a widely used environmental estrogen-like chemical that has a weak estrogenic activity. This study aimed to test the potential inhibitory effects of BPA on meiotic cell cycle progression, centrosomes and spindle integrity in mouse cumulus–oocyte complexes (COCs). They were exposed to BPA (10–30 μM; 2.3–6.8 ppm) during meiosis-I and the formation of metaphase-II (M-II) spindle. Exposure to BPA during meiosis-I caused a dose-dependent retardation/inhibition of cell cycle progression; 74 and 61% of cells reached metaphase-I (M-I) in the presence of 10 and 30 μM BPA, respectively, (81% in controls, P<0.001). A more striking delay was noted when oocytes were exposed to BPA during the formation of M-II spindle, i.e. 61 and 41% of cells (94% in controls, P<0.001) reached M-II while the remaining cells remained at M-I. Depending on dose, both (i) loosening and elongation of meiotic spindles and (ii) compaction and dispersion of pericentriolar material (PCM) were noted in all samples, all of which resulted in a series of spindle abnormalities. Interestingly, no chromosome was detected in the first polar body after the 10 and 30 μM BPA treatments. When the cells were freed from BPA exposure at 10 and 30 μM, 70 and 61%, of the cells succeeded in reaching M-II (93% in controls, P<0.001), respectively. In conclusion, one mode of action of BPA is a moderately severe yet reversible delay in the meiotic cell cycle, possibly by a mechanism that degrades centrosomal proteins and thus perturbs the spindle microtubule organization and chromosome segregation.

A. Tulga Ulus, Ceren Mungan, Murat Kurtoglu, Ferda Topal Celikkan, Mesut Akyol, Merve Sucu, Mustafa Toru, Serdar Savas Gul, Ozgur Cinar, Alp Can. IJSC -0001;0:. https://doi.org/10.15283/ijsc20075

It has been previously demonstrated that human umbilical cord stroma-derived stem cells (HUCSCs) are competent to differentiate into adipocytes. However, controversies have arisen as to whether HUCSCs can become mature adipocytes or not, and to what extent these cells can be induced in adipogenic pathway. Here, we extensively analyzed their adipogenic potency with a structural and functional approach by determining lipid formation dynamics in concordance to adipocyte-specific markers. During a 35-day period, HUCSCs respond to adipogenic induction, at which point 88% of cells exhibited multilocular lipid granules (LGs) having a mean diameter of 3 μm in round-shaped, F-actin-poor cells. Although the 1st week of induction did not generally display typical lipidogenic phenotypes, the degree of adipogenesis was dissected and confirmed by mRNA expressions of peroxisome proliferator-activated receptor γ, C/EBP-β, sterol regulatory element-binding transcription factor 1, adipophilin, stearoyl-CoA desaturase, glycerol 3-phosphate dehydrogenase 1, LIPE, adiponectin, and leptin. All markers tested were found elevated in various amounts (3–70-fold) around day 7 and reached a plateau after day 14 or 21 (5–335-fold). Perilipin as a surface protein around the LGs was confined exclusively to the enlarging LGs. Conclusively, we propose that after the termination of proliferation, HUCSCs possess the biochemical and cellular machinery to successfully differentiate into maturing adipocytes under adipogenic conditions, and this feature will ultimately allow these fetus-derived stem cells to be used for various therapeutic or esthetic purposes. Disclosure of potential conflicts of interest is found at the end of this article.