Browsing by Subject "mesenchymal stem cells"

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  • Sinha, Snehadri; Narjus-Sterba, Matilda; Tuomainen, Katja; Kaur, Sippy; Seppänen-Kaijansinkko, Riitta; Salo, Tuula; Mannerström, Bettina; Al-Samadi, Ahmed (2020)
    Mesenchymal stem cells (MSCs) are commonly isolated from bone marrow and adipose tissue. Depending on the tissue of origin, MSCs have different characteristics and physiological effects. In various cancer studies, MSCs have been found to have either tumor-promoting or tumor-inhibiting action. This study investigated the effect of adipose tissue-MSCs (AT-MSCs) and bone marrow-MSCs (BM-MSCs) on global long interspersed nuclear element-1 (LINE-1) methylation, the expression level of microenvironment remodeling genes and cell proliferation, migration and invasion of oral tongue squamous cell carcinoma (OTSCC). Additionally, we studied the effect of human tongue squamous carcinoma (HSC-3)-conditioned media on LINE-1 methylation and the expression of microenvironment remodeling genes in AT-MSCs and BM-MSCs. Conditioned media from HSC-3 or MSCs did not affect LINE-1 methylation level in either cancer cells or MSCs, respectively. In HSC-3 cells, no effect of MSCs-conditioned media was detected on the expression ofICAM1, ITGA3orMMP1. On the other hand, HSC-3-conditioned media upregulatedICAM1andMMP1expression in both types of MSCs. Co-cultures of AT-MSCs with HSC-3 did not induce proliferation, migration or invasion of the cancer cells. In conclusion, AT-MSCs, unlike BM-MSCs, seem not to participate in oral cancer progression.
  • Mannerström, Bettina; Kornilov, Roman; Abu-Shahba, Ahmed G.; Chowdhury, Iftekhar M.; Sinha, Snehadri; Seppänen-Kaijansinkko, Riitta; Kaur, Sippy (2019)
    Extracellular vesicles (EVs) are central to intercellular communication and play an important role in cancer progression and development. Osteosarcoma (OS) is an aggressive bone tumour, characterized by the presence of malignant mesenchymal cells. The specific tumour-driving genetic alterations that are associated with OS development are currently poorly understood. Mesenchymal stem cells (MSCs) of osteogenic lineage have been postulated as likely candidates as the cells of origin for OS, thus indicating that MSCs and OS stroma cells may be related cell types. Therefore, this study set out to examine the EV-mediated intercellular crosstalk of MSCs and OS. MSCs and pre-osteoblasts were treated with OS-EVs at different time points, and the epigenetic signature of OS-EVs was assessed by methylation analysis of LINE-1 (long interspersed element) and tumour suppressor genes. In addition, surface markers and expression of specific genes were also evaluated. Our data indicated that OS-EVs mediated LINE-1 hypomethylation in MSCs, whereas an opposite effect was seen in pre-osteoblasts, indicating that MSCs but not pre-osteoblasts were susceptible to epigenetic transformation. Thus, OS-EVs modulated the fate of MSCs by modulating the epigenetic status, and also influenced the expression of genes related to bone microenvironment remodelling. Overall, this study provided evidence that epigenetic regulation appears to be an early event in the transformation of MSCs during the development of OS. Elucidating the mechanisms of EV-mediated communication may lead to new avenues for therapeutic exploitation.
  • Mörtengren, Ariel (Helsingfors universitet, 2016)
    The field of stem cell research is hotter than ever, because still today, the goal for easily achievable stem cells for the use of tissue engineering and stem cell therapies, is yet to be achieved. Also, human stem cell based test systems are potential replacements of present animal test models. The ongoing obesity epidemic creates pressure for scientists to resolve the causes behind it. One way of approaching the problem, is the study of adipogenesis with the use of a in-vitro cell model. This have already been done for a while, with rodent based cell models, but the present study took the human obesity research a bit closer to its subject by using humane adipose tissue derived mesenchymal stem cells (hASC). Also, the adipogenic induction is executed with a human adipose tissue extract (ATE). Epidemiologically, the rise in obesity rates correlates at some level, with the occurrence of known endocrine disrupting chemicals in our environment. These include e.g. some pesticides and plasticizers, such as tributyltin (TBT), bis(2-ethylhexyl)phthalate (DEHP) and bisphenol A (BPA). In the present study, the effects of a variety of concentrations, ranging from 50nM to 100µM of BPA, on ATE induced adipogenesis of hASCs, was studied. The accumulation of triglycerides - a key parameter for adipogenesis - is evaluated with the use of oil-red-o (ORO) staining and photometric measurements. A set of tests was executed to find out if BPA possesses adipogenic, synergistic or antiadipogenic properties in this particular test system. No significant antiadipogenic, nor synergistic effects were seen. Some antiadipogenic effects were seen throughout the study, but without any dose-dependence. This study also showed need for further development of the test. ORO staining needs to be further standardized to increase accuracy, different batches of ATE may cause variation in the results. All and all the test system is relatively easily modified and when fully functional, it is a great tool for screening for substances affecting our adipose tissue, and also for enhancing our knowledge on human adipogenesis in whole.
  • Tigistu-Sahle, Feven (Helsingfors universitet, 2012)
    In addition to being structural components of biological membranes and energy storage of cells, lipids have recently been found to participate as essential players in cell signaling, subcellular transport mechanisms, adjusting functions of integral proteins, and regulation of cell growth and apoptosis. In this study electrospray ionization mass spectrometry (ESI-MS) techniques were used to analyze the phospholipid composition of human bone marrow derived mesenchymal stem cells (BMSC). Numerous chemically distinct lipid species were quantified and the changes in their relative amounts i.e. in the cell’s lipid profile after sequential passaging were followed until senescence (usually from passage 4 up to passage 10, in some cases until p14). Subsequently, the total lipids extracted from the cell pellets were analyzed by triple quadrupole ESI-MS equipment and using lipid-class specific scanning modes. The BMSC lines studied originated from ten donors, five of which were young and five elderly individuals. In culture, the BMSC from both young and aged donors showed time-dependent changes in their phospholipid profiles. The clearest marker findings among individual lipid species were that in phosphatidylcholines (PC) and phosphatidylethanolamines (PE), the species 38:4 (acyl chain pair 18:0/20:4n-6) largely increased towards the late passages, which was seen in the BMSC derived from both the young or aged donors. Thus the reserves of 20:4n-6, the precursor of the eicosanoids having antiproliferative, apoptotic and inflammatory cellular reactions, were increased towards late passages. At phospholipid class level, lysophosphatidylcholine (LysoPC) and phosphatidylinositol (PI) totals, and the ratio of total PI to total phosphatidylserine (PI:PS) were increased from early to latest passages. The results provide new lipid biomarkers to be used for stem cell quality control. The accumulation of polyunsaturated lipid species containing 20:4n-6 or the increase of PI: PS ratio could be potential markers for cell aging and the cells’ poor viability and functionality. The results can be used to develop efficient stem cell therapies and improve patient safety.