RESUMEN
This study is aimed to reveal morphological and functional changes in multipotent mesenchymal stromal cells (MSCs) isolated from the rat bone marrow after: (i) activation of Toll-like receptors (TLRs) with teichoic acid (TA), (ii) impact on epidermal growth factor (EGF) receptors with activator EGF or inhibitor Herceptin, and (iii) treatment with DNA intercalator Cisplatin. According to our results, TA and EGF cause an increase in the synthesis of glycosaminoglycans, c-Myc content, and protein in the MSC cytoplasm. It was observed that the cell population in G0 phase decreased and the cell population in G1 phase increased, when compared with control. At the same time, the cell population with a higher nuclear-cytoplasmic ratio (NCR) in S and G2 phases also increased. This indicates the manifestation of the MSC mesenchymal phenotype, exhibiting indirect metabolic signs of the regenerative potential increase. In other experiments, Herceptin was shown to suppress only the stemness signs of MSCs, while Cisplatin seriously affected cell viability in general, reducing synthetic and proliferative activities and causing cell morphology disturbances. © 2018 International Society for Advancement of Cytometry.
Asunto(s)
Cisplatino/farmacología , Factor de Crecimiento Epidérmico/farmacología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Animales , Células de la Médula Ósea/química , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Receptores ErbB/agonistas , Receptores ErbB/antagonistas & inhibidores , Citometría de Flujo , Glucógeno/metabolismo , Glicosaminoglicanos/biosíntesis , Glicosaminoglicanos/metabolismo , Humanos , Sustancias Intercalantes/farmacología , Masculino , Células Madre Mesenquimatosas/química , Proteínas Proto-Oncogénicas c-myc/metabolismo , Ratas , Ácidos Teicoicos/farmacología , Receptores Toll-Like/metabolismo , Trastuzumab/farmacologíaRESUMEN
We have investigated the characteristics of human hematopoietic progenitor cells (HPCs) with the CD34(+)CD45(low)SSC(low) phenotype from full-term placental tissue (FTPT) as compared to cord blood (CB) and fetal liver (FL) cells. We demonstrated the presence of cell subpopulations at various stages of the differentiation with such immunophenotypes as CD34(+/low)CD45(low/-), CD34(++)CD45(low/-), CD34(+++)CD45(low/-), CD34(+/low)CD45(hi), and CD34(++)CD45(hi) in both first trimester placental tissue (FiTPT) and FTPT which implies their higher phenotypic heterogeneity compared to CB. HPCs of the FTPT origin expressed the CD90 antigen at a higher level compared to its expression by the CB HPCs and the CD133 antigen expression being at the same level in both cases. The HPCs compartment of FTPT versus CB contained higher number of myeloid and erythroid committed cells but lower number of myeloid and lymphoid ones compared to FL HPCs. HPCs of the FTPT and CB origin possess similar potentials for the multilineage differentiation in vitro and similar ratios of myeloid and erythroid progenitors among the committed cells. This observation suggests that the active hematopoiesis occurs in the FTPT. We obtained viable HPCs from cryopreserved placental tissue fragments allowing us to develop procedures for banking and testing of placenta-derived HPCs for clinical use.