@article{MTMT:33893006, title = {Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes–A feasibility study}, url = {https://m2.mtmt.hu/api/publication/33893006}, author = {Marx, Anita and Osváth, Magdolna and Szikora, Bence and Pipek, Orsolya Anna and Csabai, István and Nagy, Ákos and Bödör, Csaba and Matula, Zsolt and Nagy, Ginette and Bors, András and Uher, Ferenc and Mikala, Gábor and Vályi-Nagy, István and Kacskovics, Imre}, doi = {10.1371/journal.pone.0285696}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {18}, unique-id = {33893006}, issn = {1932-6203}, abstract = {The need for sensitive monitoring of minimal/measurable residual disease (MRD) in multiple myeloma emerged as novel therapies led to deeper responses. Moreover, the potential benefits of blood-based analyses, the so-called liquid biopsy is prompting more and more studies to assess its feasibility. Considering these recent demands, we aimed to optimize a highly sensitive molecular system based on the rearranged immunoglobulin (Ig) genes to monitor MRD from peripheral blood. We analyzed a small group of myeloma patients with the high-risk t(4;14) translocation, using next-generation sequencing of Ig genes and droplet digital PCR of patient-specific Ig heavy chain (IgH) sequences. Moreover, well established monitoring methods such as multiparametric flow cytometry and RT-qPCR of the fusion transcript IgH :: MMSET (IgH and multiple myeloma SET domain-containing protein) were utilized to evaluate the feasibility of these novel molecular tools. Serum measurements of M-protein and free light chains together with the clinical assessment by the treating physician served as routine clinical data. We found significant correlation between our molecular data and clinical parameters, using Spearman correlations. While the comparisons of the Ig-based methods and the other monitoring methods (flow cytometry, qPCR) were not statistically evaluable, we found common trends in their target detection. Regarding longitudinal disease monitoring, the applied methods yielded complementary information thus increasing the reliability of MRD evaluation. We also detected indications of early relapse before clinical signs, although this implication needs further verification in a larger patient cohort.}, keywords = {multiple myeloma; liquid biopsy; circulating tumor DNA; next-generation sequencing (NGS); Circulating tumor cells; minimal residual disease (MRD); Droplet digital PCR (ddPCR); immunoglobulin genes}, year = {2023}, eissn = {1932-6203}, orcid-numbers = {Marx, Anita/0000-0001-8969-5766; Szikora, Bence/0000-0002-0766-5684; Pipek, Orsolya Anna/0000-0001-8109-0340; Csabai, István/0000-0001-9232-9898; Bödör, Csaba/0000-0002-0729-692X; Bors, András/0000-0003-2109-4678; Uher, Ferenc/0000-0001-7997-6142; Kacskovics, Imre/0000-0002-0402-3862} } @article{MTMT:32897456, title = {A súlyos akut légzőszervi szindrómát okozó koronavírus-2 elleni immunválasz}, url = {https://m2.mtmt.hu/api/publication/32897456}, author = {Uher, Ferenc and Matula, Zsolt and Gönczi, Márton and Gopcsa, László and Bekő, Gabriella and Réti, Marienn Györgyi and Szekanecz, Zoltán and Ajzner, Éva and Vályi-Nagy, István}, doi = {10.1556/650.2022.32521}, journal-iso = {ORV HETIL}, journal = {ORVOSI HETILAP}, volume = {163}, unique-id = {32897456}, issn = {0030-6002}, abstract = {Coronavirus disease 2019 (COVID-19) displays tremendous inter-individual variability, ranging from asymptomatic infections to life-threatening illness. Although more studies are needed, a picture has begun to emerge that variability in the immune system components is a main contributor to the heterogeneous disease courses. Here, we provide a concept for the interaction of the innate and adaptive immune systems with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to link the observations that have been made during the first two years of the pandemic. Inborn errors of, and autoantibodies directed against, type I interferons, dysregulated myeloid response, hyperinflammation, lymphopenia, lymphocyte impairment, and heterogeneous adaptive immunity to SARS-CoV-2 are discussed, as well as their impact in the course of COVID-19. In addition, we will also review part of the key findings that have helped define and delineate some of the essential attributes of SARS-CoV-2-specific humoral and cell-mediated immune memory. Orv Hetil. 2022; 163(20): 774-787.}, keywords = {ANTIBODIES; INTERFERON; Cytokines; innate immunity; ADAPTIVE IMMUNITY; citokinek; ellenanyagok; B and T cell memory; B- és T-sejt-memória; adaptív immunitás; természetes immunitás}, year = {2022}, eissn = {1788-6120}, pages = {774-787}, orcid-numbers = {Uher, Ferenc/0000-0001-7997-6142} } @article{MTMT:30407799, title = {A vérképzőőssejt-niche szerepe a hematológiai neopláziák iniciációjában és progressziójában}, url = {https://m2.mtmt.hu/api/publication/30407799}, author = {Matula, Zsolt and Mikala, Gábor and Suhajdáné Urbán, Veronika and Vályi-Nagy, István and Uher, Ferenc}, doi = {10.1556/2068.2018.51.3.3}, journal-iso = {HEMATOLÓGIA-TRANSZFUZIOLÓGIA}, journal = {HEMATOLÓGIA-TRANSZFUZIOLÓGIA}, volume = {51}, unique-id = {30407799}, issn = {1786-5913}, year = {2018}, pages = {123-133}, orcid-numbers = {Suhajdáné Urbán, Veronika/0000-0003-0393-5891; Uher, Ferenc/0000-0001-7997-6142} } @book{MTMT:3398186, title = {Őssejt-biológia}, url = {https://m2.mtmt.hu/api/publication/3398186}, isbn = {9789632266213}, author = {Uher, Ferenc}, publisher = {Medicina Könyvkiadó Zrt.}, unique-id = {3398186}, keywords = {Stem Cells; ŐSSEJTEK; Sejtbiológiatanulmányok; Stem Cellstherapy; Stem cells.}, year = {2017}, orcid-numbers = {Uher, Ferenc/0000-0001-7997-6142} } @article{MTMT:3190067, title = {Characterization and therapeutic application of canine adipose mesenchymal stem cells to treat elbow osteoarthritis}, url = {https://m2.mtmt.hu/api/publication/3190067}, author = {Kriston-Pál, Éva and Czibula, Ágnes and Gyuris, Z and Balka, Gyula and Seregi, A and Sükösd, Farkas and Süth, Miklós and Kiss-Tóth, E and Haracska, Lajos and Uher, Ferenc and Monostori, Éva}, journal-iso = {CAN J VET RES}, journal = {CANADIAN JOURNAL OF VETERINARY RESEARCH-REVUE CANADIENNE DE RECHERCHE VETERINAIRE}, volume = {81}, unique-id = {3190067}, issn = {0830-9000}, abstract = {Visceral adipose tissue (AT) obtained from surgical waste during routine ovariectomies was used as a source for isolating canine mesenchymal stem cells (MSCs). As determined by cytofluorimetry, passage 2 cells expressed MSC markers CD44 and CD90 and were negative for lineage-specific markers CD34 and CD45. The cells differentiated toward osteogenic, adipogenic, and chondrogenic directions. With therapeutic aims, 30 dogs (39 joints) suffering from elbow dysplasia (ED) and osteoarthritis (OA) were intra-articularly transplanted with allogeneic MSCs suspended in 0.5% hyaluronic acid (HA). A highly significant improvement was achieved without any medication as demonstrated by the degree of lameness during the follow-up period of 1 y. Control arthroscopy of 1 transplanted dog indicated that the cartilage had regenerated. Histological analysis of the cartilage biopsy confirmed that the regenerated cartilage was of hyaline type. These results demonstrate that transplantation of allogeneic adipose tissue-derived mesenchymal stem cells (AT-MSCs) is a novel, noninvasive, and highly effective therapeutic tool in treating canine elbow dysplasia. © 2017, Canadian Veterinary Medical Association. All rights reserved.}, year = {2017}, eissn = {1928-9022}, pages = {73-78}, orcid-numbers = {Czibula, Ágnes/0000-0003-4461-2773; Uher, Ferenc/0000-0001-7997-6142; Monostori, Éva/0000-0002-7442-3562} } @article{MTMT:3139863, title = {Quo vadis, hematológia?}, url = {https://m2.mtmt.hu/api/publication/3139863}, author = {Matula, Zsolt and Kudlik, Gyöngyi and Suhajdáné Urbán, Veronika and Uher, Ferenc}, doi = {10.1556/650.2016.30580}, journal-iso = {ORV HETIL}, journal = {ORVOSI HETILAP}, volume = {157}, unique-id = {3139863}, issn = {0030-6002}, abstract = {For decades, developing hematopoietic cells have been strictly compartmentalized into a small population of multipotent self-renewing hematopoietic stem cells, multipotent hematopoietic progenitor cells that are undergoing commitment to myeloid or lymphoid fates, and unipotent precursor cells that mature towards peripheral blood and immune cells. Recent studies, however, have provided a battery of findings that cannot be explained by this "classical" hierarchical model for the architecture of hematopoiesis. It is emerging that heterogeneous hematopoietic stem cell populations in the bone marrow coexist, each with distinct, preprogrammed differentiation and proliferation behaviors. Three subsets can be distinguished among them: myeloid-biased (alpha), balanced (beta), and lymphoid-biased (gamma/delta) hematopoietic stem cells. The ratio of these hematopoietic stem cell subsets is developmentally regulated in the foetal liver and hematopoietic stem cells adult bone marrow, and coordinately gives rise to hematopoiesis. Beta- and gamma/delta-hematopoietic stem cells are found predominantly early in the life of an organism, whereas alpha-hematopoietic stem cells accumulate in aged mice and humans. In addition, new sophisticated genetic experiments in mice have identified a major role of long-lived, committed progenitor cells downstream from hematopoietic stem cells as drivers of normal adult hematopoiesis, and revealed that post-transplantation hematopoiesis differs qualitatively and quantitatively from normal steady-state hematopoiesis. These findings have important implications for understanding in situ the regulation of haematopoiesis in health and disease. Orv. Hetil., 2016, 157(46), 1819-1829.}, year = {2016}, eissn = {1788-6120}, pages = {1819-1829}, orcid-numbers = {Suhajdáné Urbán, Veronika/0000-0003-0393-5891; Uher, Ferenc/0000-0001-7997-6142} } @article{MTMT:3124141, title = {The scaffold protein Tks4 is required for the differentiation of mesenchymal stromal cells (MSCs) into adipogenic and osteogenic lineages}, url = {https://m2.mtmt.hu/api/publication/3124141}, author = {Dülk, Metta and Kudlik, Gyöngyi and Fekete, Anna and Ernszt, Dávid and Kvell, Krisztián and Pongrácz, Judit and Merő, Balázs László and Szeder, Bálint and Radnai, László and Geiszt, Miklós and Csecsy, DE and Kovács, Tamás and Uher, Ferenc and Lányi, Árpád and Vas, Virág and Buday, László}, doi = {10.1038/srep34280}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {6}, unique-id = {3124141}, issn = {2045-2322}, abstract = {The commitment steps of mesenchymal stromal cells (MSCs) to adipogenic and other lineages have been widely studied but not fully understood. Therefore, it is critical to understand which molecules contribute to the conversion of stem cells into differentiated cells. The scaffold protein Tks4 plays a role in podosome formation, EGFR signaling and ROS production. Dysfunction of Tks4 causes a hereditary disease called Frank-ter Haar syndrome with a variety of defects concerning certain mesenchymal tissues (bone, fat and cartilage) throughout embryogenic and postnatal development. In this study, we aimed to analyze how the mutation of Tks4 affects the differentiation potential of multipotent bone marrow MSCs (BM-MSCs). We generated a Tks4 knock-out mouse strain on C57Bl/6 background, and characterized BM-MSCs isolated from wild type and Tks4-/- mice to evaluate their differentiation. Tks4-/- BM-MSCs had reduced ability to differentiate into osteogenic and adipogenic lineages compared to wild type. Studying the expression profile of a panel of lipid-regulated genes during adipogenic induction revealed that the expression of adipogenic transcription factors, genes responsible for lipid droplet formation, sterol and fatty acid metabolism was delayed or reduced in Tks4-/- BM-MSCs. Taken together, these results establish a novel function for Tks4 in the regulation of MSC differentiation.}, year = {2016}, eissn = {2045-2322}, orcid-numbers = {Kvell, Krisztián/0000-0001-8609-6274; Pongrácz, Judit/0000-0002-0278-5556; Kovács, Tamás/0000-0003-4127-4545; Uher, Ferenc/0000-0001-7997-6142; Buday, László/0000-0003-3518-5757} } @article{MTMT:3115599, title = {Mesenchymal stem cells promote macrophage polarization toward M2b-like cells.}, url = {https://m2.mtmt.hu/api/publication/3115599}, author = {Kudlik, Gyöngyi and Hegyi, B and Czibula, Ágnes and Monostori, Éva and Buday, László and Uher, Ferenc}, doi = {10.1016/j.yexcr.2016.08.022}, journal-iso = {EXP CELL RES}, journal = {EXPERIMENTAL CELL RESEARCH}, volume = {348}, unique-id = {3115599}, issn = {0014-4827}, abstract = {Mesenchymal stem or stromal cells (MSCs) act on different components of the immune response including macrophages (MPhis). Therefore this study has been committed to explore how MSCs may modify the effect of MPhi polarization upon an inductive environment using mouse bone marrow (BM)-derived "naive", unpolarized MPhis. Phagocytosis of various MPhi subtypes was different since M1 and M2b showed poorer, while M2a higher rate of phagocytosis. MSCs significantly promoted yeast ingestion by M1 and M2b and diminished it by M2a cells. Under polarizing conditions, MSCs profoundly affected the TNFalpha production of MPhi subtypes since M1 and M2b MPhis produced less and M2a produced higher amount of TNFalpha while the amount of IL-10 was not affected. The most striking effect of MSCs was registered on M2b cells since the inflammatory TNFalpha dominance remarkably shifted to the immunosuppressive IL-10. Prepolarized M1 cells readily converted to M2a and M2b states when polarizing conditions changed from M1 to M2a or M2b induction, respectively. Repolarizing from M1 to M2a resulted in the decline of IL-10 and TNFalpha and defined elevation of Ym1 similar to levels characteristic to M2a primarily polarized from naive BM-MPhis. Similarly, polarization of M1 to M2b MPhis was successful showing increase in IL-10 and reduction in TNFalpha levels characteristic to M2b cells. However, when co-culturing with MSCs, M1-M2a or M1-M2b transition was not affected. Crosstalk between MPhis and MSCs depended on PGE-2 since COX-2 inhibition reduced the effect of MSCs to establish an IL-10-dominant cytokine production by MPhis.}, year = {2016}, eissn = {1090-2422}, pages = {36-45}, orcid-numbers = {Czibula, Ágnes/0000-0003-4461-2773; Monostori, Éva/0000-0002-7442-3562; Buday, László/0000-0003-3518-5757; Uher, Ferenc/0000-0001-7997-6142} } @article{MTMT:3115524, title = {In vitro characterization of human mesenchymal stem cells isolated from different tissues with a potential to promote complex bone regeneration.}, url = {https://m2.mtmt.hu/api/publication/3115524}, author = {Szepesi, Áron and Matula, Zsolt and SZIGETI, A and Várady, György and Szalma, József and Szabó, Gyula and Uher, Ferenc and Sarkadi, Balázs and Német, Katalin}, doi = {10.1155/2016/3595941}, journal-iso = {STEM CELLS INT}, journal = {STEM CELLS INTERNATIONAL}, volume = {2016}, unique-id = {3115524}, issn = {1687-966X}, year = {2016}, eissn = {1687-9678}, orcid-numbers = {Várady, György/0000-0003-2012-9680; Szalma, József/0000-0002-6006-8758; Uher, Ferenc/0000-0001-7997-6142; Sarkadi, Balázs/0000-0003-0592-4539} } @article{MTMT:3110431, title = {The role of extracellular vesicle and tunneling nanotube-mediated intercellular cross-talk between mesenchymal stem cells and human peripheral T cells.}, url = {https://m2.mtmt.hu/api/publication/3110431}, author = {Matula, Zsolt and Németh, Andrea and Lőrincz, Péter and Szepesi, Áron and Brózik, Anna and Buzás, Edit Irén and Lőw, Péter and Német, Katalin and Uher, Ferenc and Suhajdáné Urbán, Veronika}, doi = {10.1089/scd.2016.0086}, journal-iso = {STEM CELLS DEV}, journal = {STEM CELLS AND DEVELOPMENT}, volume = {25}, unique-id = {3110431}, issn = {1547-3287}, abstract = {The role of extracellular vesicles in mediating the immunosuppressory properties of mesenchymal stem cells has recently attracted remarkable scientific interest. The aim of this work was to analyze the transport mechanisms of membrane and cytoplasmic components between T lymphocytes and adipose tissue-derived mesenchymal stem cells, by focusing on the role of distinct populations of extracellular vesicles, direct cell-cell contacts and the soluble mediators per se in modulating T lymphocyte function. We found that neither murine thymocytes and human primary T cells, nor Jurkat lymphoblastoid cells incorporated appreciable amounts of MSC-derived microvesicles or exosomes. Moreover, these particles had no effect on the proliferation and IFN-gamma production of in vitro stimulated primary T cells. In contrast, AD-MSCs incorporated large amounts of membrane components from T cells as an intensive uptake of exosomes and microvesicles could be observed. Interestingly, we found a bi-directional exchange of cytoplasmic components between human AD-MSCs and primary T lymphocytes, mediated by tunneling nanotubes derived exclusively from the T cells. In contrast, tunneling nanotubes couldn't be observed between AD-MSCs and the Jurkat cells. Our results reveal a novel and efficient way of intercellular communication between MSCs and T cells, and may help a better understanding of the immunomodulatory function of MSCs.}, year = {2016}, eissn = {1557-8534}, pages = {1818-1832}, orcid-numbers = {Németh, Andrea/0000-0002-0015-8436; Lőrincz, Péter/0000-0001-7374-667X; Buzás, Edit Irén/0000-0002-3744-206X; Lőw, Péter/0000-0003-2450-7087; Uher, Ferenc/0000-0001-7997-6142; Suhajdáné Urbán, Veronika/0000-0003-0393-5891} }