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1. Umbilical Cord Mesenchymal Stem Cell Secretome: A Potential Regulator of B Cells in Systemic Lupus Erythematosus.

Author

Yordanova, Adelina, Ivanova, Mariana, Tumangelova-Yuzeir, Kalina, Angelov, Alexander, Kyurkchiev, Stanimir, Belemezova, Kalina, Kurteva, Ekaterina, Kyurkchiev, Dobroslav, and Ivanova-Todorova, Ekaterina

Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Phenotypes Determined by Cluster Analysis in Moderate to Severe Bronchial Asthma

Author

Youroukova Vania M., Dimitrova Denitsa G., Valerieva Anna D., Lesichkova Spaska S., Velikova Tsvetelina V., Ivanova-Todorova Ekaterina I., and Tumangelova-Yuzeir Kalina D.

Subjects
asthma, phenotypes, cluster analysis, Medicine
Abstract

Background: Bronchial asthma is a heterogeneous disease that includes various subtypes. They may share similar clinical characteristics, but probably have different pathological mechanisms.

Published
2017
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7. Alteration of Mesenchymal Stem Cells Isolated from Glioblastoma Multiforme under the Influence of Photodynamic Treatment

Author

Tumangelova-Yuzeir, Kalina, primary, Minkin, Krassimir, additional, Angelov, Ivan, additional, Ivanova-Todorova, Ekaterina, additional, Kurteva, Ekaterina, additional, Vasilev, Georgi, additional, Arabadjiev, Jeliazko, additional, Karazapryanov, Petar, additional, Gabrovski, Kaloyan, additional, Zaharieva, Lidia, additional, Genova, Tsanislava, additional, and Kyurkchiev, Dobroslav, additional

Published
2023
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26. A study of the transformation of umbilical cord mesenchymal stem cells by interferon-gamma.

Author

Belemezova, Kalina, Bochev, Ivan, Ivanova-Todorova, Ekaterina, Kyurkchiev, Stanimir, and Kyurkchiev, Dobroslav

Subjects
MESENCHYMAL stem cells, UMBILICAL cord, INTERFERON gamma, CYTOKINES, THERAPEUTICS
Abstract

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-γ (IFNγ). Materials and Methods: Human MSCs from the umbilical cord were isolated, expanded, and treated with IFNγ. Primed cells were analyzed to define their ability to form colonies, their morphology, differentiation potential, proliferation, and apoptosis rate. Results: UCMSCs treated with IFNγ changed their fibroblast-like morphology and retained the expression of typical MSCs markers. IFNγ 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 IFNγ, 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. IFNγ 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 IFNγ [ABSTRACT FROM AUTHOR]

Published
2021
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28. Cultured Cells Isolated from CNS Indolent B- Cell Lymphoma Have Characteristics of Mesenchymal Stem Cells: A Clinical Case and Scientific Research

Author

Tumagelova-Yuzeir, Kalina, Ivanova-Todorova, Ekaterina, Naydenov, Emanuil, Velikova, Tsvetelina, Krasimirova, Ekaterina, Belemezova, Kalina, Dikov, Tihomir, Penkov, Marin, Nachev, Sevdalin, Genova, Margarita, and Kyurkchiev, Dobroslav

Subjects
Immunomodulation, CNS lymphoma, Mesenchymal stem cells, Case Report, Indolent B- cell lymphoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Indolent B-cell lymphoma
Abstract

The case report presented here describes the culturing and characterization of mesenchymal stem cells (MSCs) isolated from a primary indolent B-cell lymphoma, located in the CNS of an immunocompetent patient. The presence of such cells in the tumor mass can further elucidate the pathogenesis of the disease and reveal possible future approaches for its treatment. We present a case report of a 61-year-old immunocompetent woman who had an episode of confusion with numbness in the right leg and the right arm, slurred and dysarthric speech and urine incontinence. The peripheral blood tests were normal. The neurological examination demonstrated a latent hemi-paresis of the right side, aphasia, discrete hypertension and bradypsychia. The ophthalmologic examination revealed left quadranopsia. Computed tomography and magnetic resonance imaging of the brain showed a 3.5 × 2.9 cm infiltrative neoplastic lesion involving the left temporal parenchyma. The morphological features and the immunophenotyping of the lymphoid cell composition were consistent with low-grade (indolent) B-lymphocyte non-Hodgkin’s lymphoma of CNS. Cells, isolated from the resected tumor mass, were cultured in vitro in medium containing 10% fetal bovine serum (FBS) and characterized by their morphology, growth, phenotype, clonogenicity and osteogenic differentiation. It was apparent that the cultured cells isolated from the indolent B- cell lymphoma located in the CNS have the basic characteristics of mesenchymal stem cells. The presence of MSCs is described for the very first time in such type of tumor. The well-known immunosuppressive properties of the MSCs may represent another mechanism favouring the tumor growth.

Published
2018

38. Dynamics of Some Routine Immunological Parameters During Anti - TNF Therapy in Patients with Crohn’s Disease

Author

Velikova, Tsvetelina Veselinova, primary, Spassova, Zoya Angelova, additional, Milatchkov, Lyuben Mitkov, additional, Panova, Dobriana Georgieva, additional, Ivanova - Todorova, Ekaterina Ivanova, additional, Tumangelova - Yuzeir, Kalina Dinkova, additional, Kurteva, Ekaterina Krasimirova, additional, Kyurkchiev, Dobroslav Stanimirov, additional, Deredjan, Siragan Arshavir, additional, Nikolov, Rosen Kirilov, additional, Altankova, Iskra Petrova, additional, and Vladimirova, Lyudmila Mateva, additional

Published
2018
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39. Serological Update on Celiac Disease Diagnostics in Adults

Author

V. Velikova, Tsvetelina, primary, A. Spassova, Zoya, additional, D. Tumangelova-Yuzeir, Kalina, additional, K. Krasimirova, Ekaterina, additional, I. Ivanova-Todorova, Ekaterina, additional, S. Kyurkchiev, Dobroslav, additional, and P. Altankova, Iskra, additional

Published
2018
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40. Abstracts from the 3rd International Severe Asthma Forum (ISAF)

Author

Ketelaar, M. E., primary, Van De Kant, K., additional, Dijk, F. N., additional, Klaassen, E. M. M., additional, Grotenboer, N., additional, Nawijn, M. C., additional, Dompeling, E., additional, Koppelman, G. H., additional, Murray, Clare, additional, Foden, Philip, additional, Lowe, Lesley, additional, Durrington, Hannah, additional, Custovic, Adnan, additional, Simpson, Angela, additional, Simpson, Andrew J., additional, Shaw, Dominick E., additional, Sousa, Ana R., additional, Fleming, Louise J., additional, Roberts, Graham, additional, Pandis, Ioannis, additional, Bansal, Aruna T., additional, Corfield, Julie, additional, Wagers, Scott, additional, Djukanovic, Ratko, additional, Chung, Kian Fan, additional, Sterk, Peter J., additional, Vestbo, Jorgen, additional, Fowler, Stephen J., additional, Tebbutt, S. J., additional, Singh, A., additional, Shannon, C. P., additional, Kim, Y. W., additional, Yang, C. X., additional, Gauvreau, G. M., additional, Fitzgerald, J. M., additional, Boulet, L. P., additional, O’Byrne, P. M., additional, Begley, N., additional, Loudon, A., additional, Ray, D. W., additional, Baos, Selene, additional, Cremades, Lucía, additional, Calzada, David, additional, Lahoz, Carlos, additional, Cárdaba, Blanca, additional, Asosingh, Kewal, additional, Lauruschkat, Chris, additional, Queisser, Kimberly, additional, Wanner, Nicholas, additional, Weiss, Kelly, additional, Xu, Weiling, additional, Erzurum, Serpil, additional, Sokolowska, Milena, additional, Chen, Li-Yuan, additional, Liu, Yueqin, additional, Martinez-Anton, Asuncion, additional, Logun, Carolea, additional, Alsaaty, Sara, additional, Cuento, Rosemarie, additional, Cai, Rongman, additional, Sun, Junfeng, additional, Quehenberger, Oswald, additional, Armando, Aaron, additional, Dennis, Edward, additional, Levine, Stewart, additional, Shelhamer, James, additional, Choi, Kilyong, additional, Lazova, Snezhina, additional, Perenovska, Penka, additional, Miteva, Dimitrinka, additional, Priftis, Stamatios, additional, Petrova, Guergana, additional, Yablanski, Vassil, additional, Vlaev, Evgeni, additional, Rafailova, Hristina, additional, Kumae, Takashi, additional, Holmes, L. J., additional, Yorke, J., additional, Ryan, D. M., additional, Chinratanapisit, Sasawan, additional, Matchimmadamrong, Khlongtip, additional, Deerojanawong, Jitladda, additional, Karoonboonyanan, Wissaroot, additional, Sritipsukho, Paskorn, additional, Youroukova, Vania, additional, Dimitrova, Denitsa, additional, Slavova, Yanina, additional, Lesichkova, Spaska, additional, Tzocheva, Iren, additional, Parina, Snezhana, additional, Angelova, Svetla, additional, Korsun, Neli, additional, Craiu, Mihai, additional, Stan, Iustina Violeta, additional, Deliu, Matea, additional, Yavuz, Tolga, additional, Sperrin, Matthew, additional, Sahiner, Umit M., additional, Belgrave, Danielle, additional, Sackesen, Cansin Sackesen, additional, Kalayci, Ömer, additional, Velikov, Petar, additional, Velikova, Tsvetelina, additional, Ivanova-Todorova, Ekaterina, additional, Tumangelova-Yuzeir, Kalina, additional, Kyurkchiev, Dobroslav, additional, Megremis, Spyridon, additional, Constantinides, Bede, additional, Sotiropoulos, Alexandros Georgios, additional, Xepapadaki, Paraskevi, additional, Robertson, David, additional, Papadopoulos, Nikolaos, additional, Wilkinson, Maxim, additional, Portsmouth, Craig, additional, Ray, David, additional, Goodacre, Royston, additional, Valerieva, Anna, additional, Bobolea, Irina, additional, Vera, Daiana Guillén, additional, Gonzalez-Salazar, Gabriel, additional, Moreno, Carlos Melero, additional, Rodriguez, Consuelo Fernandez, additional, De Las Cuevas Moreno, Natividad, additional, Wang, R., additional, Satia, I., additional, Niven, R., additional, Smith, J. A., additional, Southworth, T., additional, Plumb, J., additional, Gupta, V., additional, Pearson, J., additional, Ramis, I., additional, Lehner, M. D., additional, Miralpeix, M., additional, Singh, D., additional, Satia, Imran, additional, Woodhead, Mark, additional, O’Byrne, Paul, additional, Smith, Jaclyn Ann, additional, Forss, Cecilia, additional, Cook, Peter, additional, Brown, Sheila, additional, Svedberg, Freya, additional, Stephenson, Katherine, additional, Bertuzzi, Margherita, additional, Bignell, Elaine, additional, Enerbäck, Malin, additional, Cunoosamy, Danen, additional, Macdonald, Andrew, additional, Liu, Caini, additional, Zhu, Liang, additional, Fukuda, Kiochi, additional, Zhang, Cunjin, additional, Ouyang, Suidong, additional, Chen, Xing, additional, Qin, Luke, additional, Rachakonda, Suguna, additional, Aronica, Mark, additional, Qin, Jun, additional, Li, Xiaoxia, additional, Larose, Marie-Chantal, additional, Archambault, Anne-Sophie, additional, Provost, Véronique, additional, Chakir, Jamila, additional, Laviolette, Michel, additional, Flamand, Nicolas, additional, Logan, Nicola, additional, Ruckerl, Dominik, additional, Allen, Judith E., additional, Sutherland, Tara E., additional, Hamelmann, E., additional, Vogelberg, C., additional, Goldstein, S., additional, Azzi, G. E., additional, Engel, M., additional, Sigmund, R., additional, Szefler, S. J., additional, Mesquita, Raquel, additional, Coentrão, Luis, additional, Veiga, Rui, additional, Paiva, José-Artur, additional, Roncon-Albuquerque, Roberto, additional, Porras, Wendy Vargas, additional, Moreno, Ana González, additional, Iglesias, Jesus Macías, additional, Ramos, Gustavo Córdova, additional, Acevedo, Yesenia Peña, additional, Alonso, Miguel Angel Tejedor, additional, Del Mar Moro Moro, Maria, additional, Krcmova, Irena, additional, Novosad, Jakub, additional, Hanania, Nicola Alexander, additional, Massanari, Marc, additional, Hecker, Heike, additional, Kassel, Eric, additional, Laforce, Craig, additional, Rickard, Kathy, additional, Snelder, Sanne, additional, Braunstahl, Gert-Jan, additional, Jones, T. L., additional, Neville, D., additional, Heiden, E. R., additional, Lanning, E., additional, Brown, T., additional, Rupani, H., additional, Babu, K. S., additional, Chauhan, A. J., additional, Eldegeir, M. Y., additional, Chapman, A. A., additional, Ferwana, M., additional, and Caldron, M., additional

Published
2017
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41. Treg/Th17 cell balance and phytohaemagglutinin activation of T lymphocytes in peripheral blood of systemic sclerosis patients

Author

Krasimirova, Ekaterina, primary, Velikova, Tsvetelina, additional, Ivanova-Todorova, Ekaterina, additional, Tumangelova-Yuzeir, Kalina, additional, Kalinova, Desislava, additional, Boyadzhieva, Vladimira, additional, Stoilov, Nikolay, additional, Yoneva, Tsvetelina, additional, Rashkov, Rasho, additional, and Kyurkchiev, Dobroslav, additional

Published
2017
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44. P-178 YI Specific mRNA Expression Profile in Inflamed Colonic Mucosa Derived from Patients with Inflammatory Bowel Disease

Author

Altankova Iskra, Ivanova-Todorova Ekaterina, Velikova Tsvetelina, Stanilova Spaska, Spassova Zoya, Karakolev Iliya, and Kyurkchiev Dobroslav

Subjects
Colonic mucosa, medicine.medical_specialty, business.industry, Mrna expression, Internal medicine, Gastroenterology, medicine, Immunology and Allergy, medicine.disease, business, Inflammatory bowel disease
Published
2014
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46. ORIGINAL ARTICLE: HLA‐G Expression Is Up‐Regulated by Progesterone in Mesenchymal Stem Cells

Author

Ivanova‐Todorova, Ekaterina, primary, Mourdjeva, Milena, additional, Kyurkchiev, Dobroslav, additional, Bochev, Ivan, additional, Stoyanova, Elena, additional, Dimitrov, Rumen, additional, Timeva, Tanya, additional, Yunakova, Maria, additional, Bukarev, Dimitar, additional, Shterev, Atanas, additional, Tivchev, Petar, additional, and Kyurkchiev, Stanimir, additional

Published
2009
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47. Female Sex Steroid Hormones Modify Some Regulatory Properties of Monocyte-Derived Dendritic Cells.

Author

Kyurkchie, Dobroslav, Ivanova-Todorova, Ekaterina, Hayrabedyan, Soren, Altankova, Iskra, and Kyurkchiev, Stanimir

Subjects
*STEROID hormones, *DENDRITIC cells, *MONOCYTES, *CYTOKINES, *PREGNANCY
Abstract

Problem Monocyte-derived dendritic cells (mDCs) are present in human decidua during the first month of pregnancy where they experience the effect of the increased concentration of progesterone (Pg) and estradiol (Estr). The aim of our study was to assess the effect of these reproductive hormones on the immunomodulatory role of mDCs. Methods of study The mDCs cultured in vitro in the presence of sex steroid hormones and characterized for their apoptosis and secretion of cytokines by flow cytometry, enzyme linked immunosorbent assay and proteome profiler kit. Results Female sex steroid hormones enhance the life cycle of mDCs, thus increasing the maturation and apoptosis, they also increase the production of interleukin (IL)-10 and IL-27 but only Pg increases the production of IL-13 and down regulates the secretion of IL-23. Conclusion The Pg and Estr participate in the regulation of the immune response during pregnancy by influencing apoptosis and the cytokine profile of the mDCs. [ABSTRACT FROM AUTHOR]

Published
2007
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50. Conditioned Medium from Adipose Tissue-Derived Mesenchymal Stem Cells Induces CD4+FOXP3+ Cells and Increases IL-10 Secretion

Author

Ivanova-Todorova, Ekaterina, Bochev, Ivan, Dimitrov, Rumen, Belemezova, Kalina, Mourdjeva, Milena, Kyurkchiev, Stanimir, Kinov, Plamen, Altankova, Iskra, and Kyurkchiev, Dobroslav

Abstract

Mesenchymal stem cells (MSCs) are a new and promising tool for therapy of autoimmune disorders. In recent years their possibility to take part in the modulation of the immune response is discussed. The exact mechanisms for immunoregulation realized by MSCs are not clear yet, but interactions with other immunoregulatory cells may be involved in this process. The investigation of the influence of MSCs on the expression of FoxP3 and cytokine secretion by T helper cells was the aim of this study. T helper cells were isolated from PBMCs by magnetic separation and MSCs were isolated from human adipose tissue, and CD4+ T cells were cultured with conditional medium of MSCs. The methods which were used include flow cytometry, ELISA, and Human Proteome profiler kits. The results demonstrated that secretory factors in MSCs conditional medium lead to increased expression of FoxP3 and increased secretion of IL-10 by T helpers. The obtained results give us opportunity to discuss the interaction between two kinds of immunoregulatory cells: MSCs and FoxP3+ T helpers. We suppose that this interaction leads to increased number of immunosuppressive helpers which secrete IL-10. MSCs provide some of their immunosuppressive functions acting on T regulatory cells, and we believe that IL-6 secreted by MSCs is involved in this process.

Published
2012
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