Molecular Immunology

  • Main research topics

    Head of Department:  Associate Professor MILENA SERGEEVA MOURDJEVA-ANDONOVA, PhD

    Main research topics

    Since 2005 the main investigation priorities of the Molecular immunology department have been mesenchymal stem cells (MSC). The protocols for isolation of MSC from different adult tissues were developed. The research on autoimmune mechanisms of some diseases of the reproductive system such as endometriosis and prostate cancer were continued as well as the studies of tumor specific antigens and neo-angiogenesis.
    The studies on differentiation and immunoregulatory properties of MSC will enable the development of new therapeutic approaches for treatment of autoimmune disorders, transplantation complications and degenerative diseases. In regenerative medicine MSC can be used for replacement of bone or skin defects and myocardial infarctions, etc.
    Main research topics in Molecular immunology department are:

    • Isolation and characterization of mesenchymal stem cells from different adult tissues and organs. Development of protocols for clinical application of mesenchymal stem cells as immunomodulatory agents in autoimmune disorders.
    • Effect of reproductive steroid hormones on expression of proteins with immunoregulation properties from mesenchymal stem cells isolated from endometrium, early deciduas, adipose tissue and bone marrow.
    • Studies on pathogenetic mechanisms and factors of endometriosis.
    • Isolation and characterization of human cancer stem cells: in search for new targets for treatment of skin carcinomas. Search for tumor stem cells specific markers.
    • Development of xeno-free conditions for culturing of human embryonic stem cells (line BG01V).
    • Development of experimental approaches for obtaining and differentiation of human indused pluripotent stem cells from mesenchymal stem cells, blood cells, etc.
    • Scientific achievements

      More important scientific achievements for the last 10 years

      Stem cells

      • The presence of mesenchymal stem cells /MSC/ has been proved in human endometrium and decidual tissue. These cells can be expanded and cultured in vitro, they possess phenotype characteristics of stromal cells of mesenchymal origin recognized by the expression of CD29, CD73 and CD90, while being negative for markers of haemopoietic cells. The endometrial MSCs possess clonogenic activity they can be differentiated to osteogenic, adipogenic and endothelium-like cells. The hypothesis that the stromal MSCs participate in the remodeling of the endometrium during the menstrual cycle of women as well as during formation of deciduas in pregnancy has been proposed. R.Dimitrov, T.Timeva, D.Kyurkchiev, M.Stamenova, A.Shterev, P.Kostova, V. Zlatkov, I.Kehayov, S.Kyurkchiev. Characterization of clonogenic stromal cells isolated from human endometrium. Reproduction, (2008) 135 551–558; R.Dimitrov, D.Kyurkchiev, T.Timeva, M.Yunakova, M.Stamenova, A. Shterev, S.Kyurkchiev. Human pre-decidual stromal cells have the characteristics of mesenchymal stem cells. Fertil. Steril, 2010, 93 (1), 210-219; S.Kyurkchiev, A.Shterev, R.Dimitrov. Assessment on presence and characteristics of multipotent stromal cells in human endometrium and deciduas. Reproductive Biomedicine Online, 2010, 20 (3), 305 – 313
      • Our investigations about the role of progesterone and other reproductive hormones on the proliferation, differentiation and immunomodulating properties of mesenchymal stem cells have shown the following results: the progesterone have not changed the proliferative properties/characteristics of bone marrow, adipose tissue or early deciduas derived mesenchymal stem cells when added to the culture medium. The combination of estradiol, progesterone and cAMP has induced the decidualization of all MSC, while the strongest effect has been obtained with the ones isolated from early deciduas. D. Kyurkchiev, E. Ivanova-Todorova, S. Kyurkchiev. New target cells of the immunomodulatory effects of progesterone. Reproductive BioMedicine Online. 2010.
      • Adipose tissue-derived mesenchymal stem cells (ASC) have been used as feeder cells for the elaboration of co-culture system for maintenance of human embryonic stem cells (hESC). For the purpose BG01V cell line have been used. In the condition of long-term co-culture (around 20 passages) with ASC, BG01V cells have preserved their pluripotency and differentiation potential for development of embryoid bodies. According to the collected experimental data it is evident that human ASC can efficiently be used as supporting feeder cells for the growth of BG01V cells in co-cultures. ASC apparently produce and secrete the necessary growth factors which maintain the growth and differentiation potential of BG01V cells. Oreshkova, T., Stoyanova, E., Mourdjeva, M., Kyurkchiev, S. Human adipose tissue-derived mesenchymal stem cells support the growth and plasticity of human embryonic stem cells (BG01V cell line). Comptes Rendus de L’Academie Bulgare des Sciences 63(10), pp. 1477- 1484. 2010
      • Laboratory protocols for derivation of iPS from ASC and human fibroblast cell line BJ have been developed. By using retroviral system, plasmids encoding the sequences of transcription factors (Oct4, Sox2, Klf4 and c-Myc) have been amplified. Having been introduced into the target cells, a change in the morphology and the expression of specific pluripotency markers have been detected in the target cells. Accumulating data from immunofluorescence labeling, RT-PCR and FACS analyses show that the treated cells have the some characteristics of human embryonic stem cells but do not express all pluripotent markers.
      • Methods for isolation, in vitro cultivation and characterization of mesenchymal stem cells from human bone marrow, adipose tissue and dental pulp have been developed. By comparison of mesenchymal stem cells from bone marrow (bm-MSC) or adipose tissue (at-MSC) we found that the cells from both sources have almost identical morphological, immunophenotype and cloning characteristics. As to the rate of in vitro proliferation we proved that at-MSCs have higher proliferative ability but lower potential for differentiation to osteogenic cells. The finding that at-MSCs have higher inhibitory activity on the synthesis of immunoglobulins than human B-cells is of particular importance, which presumes their application as immunomodulator in clinical practices. Bochev, I., G. Elmadjian, D. Kyurkchiev, L. Tzvetanov, I. Altankova, P. Tivchev, S. Kyurkchiev. Mesenchymal stem cells from human bone marrow or adipose tissue differently modulate mitogen-stimulated B-cell immunoglobulin production in vitrо. Cell Biol Internatl., 32, 384 – 393. 2008; I.Bochev, S.Kyurkchiev. Immunomodulatory effects of human bone marrow or adipose tissue derived mesenchymal stem cells on T-helper cell cytokine production in vitro. Comptes Rendus de L’Academie Bulgare des Sciences 62 (12), pp. 1553-1558. 2009.
      • During characterization of cells isolated from umbilical cord vein we found that according to their morphological and immunophenotype characteristic they belong to the family of mesenchymal stem cells (uc-MSC). These cells express survivin, bcl-2, vimentin and endoglin, which is proved at in vivo protein level with antibodies and at in vivo mRNA level through RT-PCR. The finding that after differentiation of these cells to endothelium-like cells there is no expression of survivin is of particular importance. This fact shows that MSCs are suitable for therapeutic use because after differentiation their proliferative potential becomes lower, i.e. there is no danger of uncontrolled growth of the transplanted cells. S.Kestendjieva, D.Kyurkchiev, G.Tsvetkova, T.Mehandjiev, A.Dimitrov, A.Nikolov, S.Kyurkchiev. Characterization of mesenchymal stem cells isolated from human umbilical cord. Cell Biol Internatl., 2008, 32,724 – 732

      Search for tumor stem cells specific markers

      • Keratinocytes from basal layer from healthy human epidermis have been isolated. In the obtained primary cultures of human keratinocytes more than 80% from the cells have been CD71dim and CD49bright, which suggests the presence of high number of stem cells with high proliferative potential. After a depletion of СD133+ cells by cell sorting, a loss of the ability of colony formation has been observed.
      • Testing of serum raised against membrane fraction of human keratinocytes have shown the appearance of two protein bands at 56.7 kDa and 49.5 kDa identified by Western blot. When comparing the reactivity of the obtained polyclonal serum against membrane and cytoplasmic fraction of human fibroblasts from cell line BJ and squamous cell carcinoma of the tongue SCC-9, the same bands have been obtained. About 30% from the keratinocytes and 10% from SCC-9 have shown specific membrane staining with granular pattern suggesting receptors grouping. This type of staining has been completely lacking in human fibroblasts from cell line BJ.

      IMMUNOREGULATION IN PREGNANCY

      • A specific monoclonal antibody Mat3A6 against progesterone induced blocking factor has been produced (PIBF). This antibody is with proven unique PIBF specificity that may be used in clinical diagnostics. By using Mat3A6, it has been demonstrated that PIBF is constitutively expressed in mesenchymal stem cells isolated from human decidua. The expression and secretion of this protein is modulated by progesterone. Ivanova-Todorova, E., D. S. Kyurkchiev, A. Nalbanski, T. Timeva, A. Shterev, S. D. Kyurkchiev. Production and characterization of a novel monoclonal antibody against progesterone induced blocking factor (PIBF). J. Reprod Immunol., 78, 94–101, 2008. Ivanova-Todorova, E., Kyurkchiev, D., Mourdjeva, M., Dimitrov, R., Stoyanova, E., Timeva, T., Yunakova, M., Shterev, A., Kyurkchiev, S. Pre-decidual multipotent stromal cells (PreDMSc) constitutively express progesterone induced blocking factor (PIBF). Comptes Rendus de L’Academie Bulgare des Sciences 2009.
      • It has been found that the progesterone induces the expression of HLA-G in human mesenchymal stem cells. The presented results prove that the progesterone induces significant changes in the physiology of human MSC by the induction of expression of factors with immunomodulatory functions. E.Ivanova-Todorova, M.Mourdjeva, D.Kyurkchiev, I.Bochev, E.Stoyanova, R.Dimitrov, T.Timeva, M.Yunakova, D.Bukarev, A.Shterev, P.Tivchev, S.Kyurkchiev. HLA-G Expression Is Up-Regulated by Progesterone in Mesenchymal Stem Cells. Am J Reprod Immunol; 2009. Mourdjeva, M., Ivanova-Todorova, E., Kyurkchiev, D., Bochev, I., Stoyanova, E., Dimitrov, R., Kyurkchiev, S. Progesterone enhances the HLA-G expression in mesenchymal stem cells. Comptes Rendus de L’Academie Bulgare des Sciences,62(12), pp.1559-1566. 2009.
      • It has been found that the female reproductive hormones – progesterone and estradiol accelerate the maturation and precipitate the apoptosis of mature human dendritic cells, i.e. they accelerate the life cycle of the dendritic cells. Both hormones lower the secretion of cytokines IL-10 and IL-27 and only progesterone increases the production of IL-13 but inhibits the secretion of IL-23. Ivanova E., D. Kyurkchiev, I. Altankova, J. Dimitrov, E. Binakova, S. Kyurkchiev. CD83+ monocyte-derived dendritic cells are present in human decidua and progesterone induces their differentiation in vitro. Amer. J. Reprod. Immunol., 53, 1-7, 2005. Kyurkchiev D., E. Ivanova-Todorova, S. Hayrabedyan, I. Altankova, S. Kyurkchiev. Female sex steroid hormones modify some regulatory properties of monocyte-derived dendritic cells. Amer. J. Reprod. Immunol., 58, 425–433, 2007. These results provide new mechanisms of the immunomodulatory effect of the reproductive steroid hormones during pregnancy in human.
      • With the help of produced monoclonal antibody 1H6 against phosphatidylserine /PS/ the externalization of PS has been investigated through flow cytometry and immunofluorescence. A model of the dynamics of externalization of PS during apoptosis has been described. The addition of progesterone in physiological doses lowers the externalization of PS in dendritic cells, T-cells and of monocyte-macrophage line U937. Mourdjeva M., D. Kyurkchiev, A. Mandinova, I. Altankova, I. Kehayov, S. Kyurkchiev. Dynamics of membrane translocation of phosphatidylserine during apoptosis detected by a monoclonal antibody. Apoptosis, 10, 209-217, 2005. Mourdjeva M., Z. Popova, D. Kyurkchiev, K. Kontinopoulou, I. Altankova, I. Kehayov, S. Kyurkchiev. Progesterone-modulated Phosohatidylserine Externalization in Apoptosis and Activation of Jurkat Cells. AJRI, 56, 1-9, 2006. The results provide new prospects for investigation of the interaction between reproductive hormones and lymphoid cells, especially in relation to their specific conditions related to autoimmunity, as apoptosis and activation.
      • Investigations aimed at establishment of cell mechanisms in the induction of autoimmune response against human beta-2 glycoprotein I /B2-GPI/ have been carried out. It has been found that human dendritic cells become differentiated in vitro and preferentially swallow through endocytosis the B2-GPI/cardiolipine complex but not the negative form of B2-GPI. Flow cytometry analysis proved that after endocytosis the dendritic cells represent epitopes which are recognized by specific monoclonal antibodies against human B2-GPI. The results show that the B2-GPI/CL complex is immunogenic and able to induce autoimmune response leading to synthesis of anti-B2-GPI antibodies. The studies show the role of cell-based immune reaction in the pathogenesis of anti-phospholipid syndrome which is one of the reasons for infertility in human.
      • Epitope specificity of the serum protein beta 2-GPI has been characterized by the employment of monoclonal and polyclonal antibodies and autoimmune and hyperimmune sera. Obtained results have given reason to make the conclusions that the molecule of beta 2-GPI is able to elicit production of different populations of antibodies, only part of which associable with pathological effects. The fact has relevance to the clarification of the role of phospholipid antibodies and in particular has bearing to the role of beta 2-GPI–dependent antibodies during an unsuccessful pregnancy. Kyurkchiev, D., Alexandrova, K., Nalbanski, A., Robeva, R., Stamenova, M., Altankova, I., Kyurkchiev,S Analysis of epitopes of beta-2-glycoprotein recognized by autoantibodies. (2002) Clinical Application of Immunology,1 (1), pp.53-57.
      • Monoclonal antibodies against the molecule of the atrial natriuretic peptide /ANP/ have been obtained. Cell-specific localization of ANP in rat testis of late fetal to puberty age has been established. The peptide is localized in the Leydig, Certoli and germ cells. The cell localization of the peptide in rat ovary during puberty and after treatment with gonadotropic hormone has been followed. The expression of ANP in all steroid-producing cells in the developing oocytes has been proved through immunocytochemistry. A.Russinova, M.Mourdjeva, C. Valkova, S.Kyurkchiev, I.Kehayov. Immunocytochemical Localization Of Atrial Natriuretic Factor (ANF) In Rat Female Reproductive Tract: Evidences For A Potential Hormonal Regulation. Biology of the cell 94 (2002) 91-98 Mourdjeva M, Russinova A, Kyurkchiev S, Kehayov I. Spatial and temporal distribution of atrial natriuretic factor in the rat testis. Biol Cell 2001 Nov 93:5 301-7. Russinova A., M.Mourdjeva, S.Kyurkchiev, I.Kehayov. Immunohistochemical detection of atrial natriuretic factor (ANF) in different ovarian cell types. Endocrine Regulation, 2001, 35, 81-89. M.Bakalska, M.Mourdjeva, A.Russinova, S.Kyurkchiev, I.Kehayov. Localization of ANP in rat testis after leydig cell destruction: evidence for a potential role in regulating gonadal function. Endocrine regulations 1999, Vol. 33, 183-191.

      ENDOMETRIOSIS

      • Immunocytochemistry and immune-enzyme methods have been applied for establishment the expression of angiogenic factors and specific tumor markers in endometrial tissue. Developed in the department antibodies against IL-1 alpha, FGF-1 and ovary carcinoma has been used. Polyclonal antibodies against S100A13 and endoglin have been used for immunocytochemistry localization of angiogeic factors. Hayrabedyan S., S. Kyurkchiev, I. Kehayov. Endoglin (CD105) and S100A13 as markers of active angiogenesis in endometriosis. Reprod. Biol., 5, /1/, 51-67, 2005. Hayrabedyan S., S. Kyurkchiev, I. Kehayov. FGF-1 and S100A13 possibly contribute to angiogenesis in endometriosis. J. Reprod. Immunol., 67, /1-2/, 87-101, 2006. Hayrabedyan, S., S. Kyurkchiev, I. Kehayov. Calcium-binding protein S100A13 is overexpressed in endometriosis – C. r. Acad. bulg Sci, 2008, 61(2), 281-288.
      • Analysis of obtained data of the peritoneal fluid content in women with and without endometriosis have revealed quality and quantity differences between patients and healthy donors, which is indicative of the existence of molecular markers with the prospective use for non-invasive diagnostic of the disease. Dimitrov, R., Nalbansky, A., Mollova, M., Stamenova, M., Kyurkchiev, S Autoantibodies in sera from women with endometriosis against components of peritoneal fluid. (2004) Clinical Application of Immunology, 3(1), pp.306-309. Zasheva, D., Dimitrov, R., Stamenova, M. Endometriosis and the role of the integrins in the pathogenesis of the endometriosis. (2007) Akusherstvo i ginekologia, 46 (5), pp. 37-48.
      • Presence of autoantibodies in sera obtained from patients with endometriosis against components of their corresponding peritoneal fluid has been documented. Data have been obtained showing the unfavourable influence of peritoneal fluid received from infertile women on spermatozoa characteristics with significance for their fertilization potential. Dimitrov, R., Nalbansky, A., Mollova, M., Stamenova, M., Kyurkchiev, S Autoantibodies in sera from women with endometriosis against components of peritoneal fluid. (2004) Clinical Application of Immunology, 3(1), pp.306-309.
      • It has been found that peritoneal fluid received from women with endometriosis can exert negative effect of on the process of decidualization of pre-decidual stromal cells in vitro. This finding is in support of the possibility for the existence of mechanism affecting the receptive capacity of women with endometriosis by components of the peritoneal fluid and may be associated with the infertility etiology of these patients.
      • It has been found that peritoneal fluid received from women with endometriosis can exert negative effect of on sperm cells’ parameters in correlation to the fertility potential of the sperm.
      • It has been found that peritoneal fluid received from women with endometriosis can exert negative effect of on the process of decidualization of pre-decidual stromal cells in vitro. This finding is in support of the possibility for the existence of mechanism affecting the receptive capacity of women with endometriosis by components of the peritoneal fluid and may be associated with the infertility etiology of these patients.

      TUMORS

      • The activity of the construct survivin-siRNA on prostate carcinoma cells PC3 has been investigated. The relative protein levels have been obtained by immunoblot of three independent experiments. The gene expression of survivin-siRNA and the control siRNA have been analyzed by real time qPCR. Both experimental settings of real time qPCR and immunoblot have shown significant decrease of mRNA and protein expression after transfection with specific siRNA of PC-3 cells. M.Mourdjeva, A.Mandinova, S.Kyurkchiev, I.Kehayov. Experimental data for inhibition of the expression of surviving by small interfering RNA molecules (siRNAs). C.r.Acad Bulg Sci, 2009.
      • The expression of low molecular mass stress proteins (alpha В-crystalline and Hsp27) in reproductive tissue and different tumors has been studied by means of immune fluorescence, Western and immunoblot, Northern blot and real time qPCR. The expression of both proteins has been demonstrated in human placenta, rat testis and human ovary. Differences have been documented showing specific patterns for alpha В- crystalline in benign and malignant tumors – high degree of expression in benign and loss of expression in malignant tumors. Mineva, I., Gartner, W., Hauser, P., Kainz, A., Löffler, M., Wolf, G., Oberbauer, R., Weissel, M., Wagner, L. Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing (2005) Cell Stress and Chaperones, 10 (3), pp. 171-184; Mineva, I., Stamenova, M., Gartner, W., Wagner, L Expression of the small heat shock protein alphaB-crystallin in term human placenta. (2008) American Journal of Reproductive Immunology,60 (5), pp. 440-448.
      • It has been proven through examination of patients with prostate carcinoma, subjected to specific DNA vaccination, that resulting from this procedure the patients develop humoral immune response which is manifested by the production of antibodies against prostate-specific membrane antigen. These results support the idea of the DNA vaccination as a possible therapeutic approach. Todorova K., S. Zoubak, M. Mincheff, S. Kyurkchiev. Biochemical Nature and mapping of PSMA epitopes recognized by human antibodies induced after immunization with gene-based vaccines. Anticancer research, 25, 4727-4732, 2005; Todorova K., I. Ignatova, S. Tchakarov, I. Altankova, S. Zoubak, S. Kyurkchiev, M. Mincheff. Humoral immune response in prostate cancer patients after immunization with gene-based vaccines that encode for a protein that is proteasomally degraded. Cancer Immunity, 5, 1-9, 2005.
      • Research grants

        Research Projects for the last 5 years

        1. DOO2-223/08, IDEAS competition, National Fund Scientific Investigations. Ministry of Education and Science. Isolation and Characterization of Human SKIN Stem Cells: a search for new targets for the therapy of skin cancer. Project leader: Prof. I. Kehayov.
        2. ТК-B-1609/2006, Ministry of Education and Science. Investigation on the possibilities for control of proliferation of tumor cells through specific iRNA mollecules. Project leader: Prof. I. Kehayov
        3. 4/2006, National Scientific Program “GENOMICS”, Investigation on the plasticity of human mesenchymal stem cells. Project leader: Prof. S. Kyurkchiev
        4. L-1523/2005, Ministry of Education and Science. Clinical and experimental characterization of specific markers for the autoimmune disease of the internal year. Project leader: Prof. S. Lolov
        5. L-1511/05, Ministry of Education and Science. Expression of low molecular mass stress proteins in human placenta under normal conditions and in pregnancy failure. Principal Investigator: Assoc. Prof. Dr. M. Stamenova.
        6. L-1517/2005, Ministry of Education and Science. Investigation on the effect of reproductive steroid hormones in proliferation and differentiation of human stem cells. Project leader: Prof. S. Kyurkchiev
        7. MUК 1406/2004, Ministry of Education and Science. Following the externalization of phosphatidylserin in cellular membrane thorugh monoclonal antibodies. Project leader: K. Ivanova – Todorova
        8. MU-L–1401/04, Ministry of Education and Science. Identification of marker proteins for endometriosis in the peritoneal fluid of patients. Principal Investigator: Roumen Dimitrov.
        9. NATO Reintegration grant 982763/2007-2010. Mitotic exit regulatory networks in human cells and cancer development Principal Investigator: Irina Alexander IMB, IBIR Partner – Diana Zasheva
        10. BAS grant. Development of laboratory protocols for derivation of induced pluripotent stem cells. Principal investigator: Milena Mourdjeva
        11. BAS grant. Development of xeno-free conditions for culturing of human embryonic stem cells (line BG01V). Principal investigator: Tsvetelina Oreshkova
        12. BAS grant. Studies on the endometriosis pathogenesis. Principal Investigator: Roumen Dimitrov.
        13. BAS grant. Pregnancy and diabetes. Principal Investigators: Katia Todorova, Kameliya Petkova

        Проекти, разработвани през последните 5 години

        1.       DOO2-223/08, IDEAS competition, National Fund Scientific Investigations. Ministry of Education and Science. Isolation and Characterization of Human SKIN Stem Cells: a search for new targets for the therapy of skin cancerProject leader: Prof. I. Kehayov.

        2.       ТК-B-1609/2006, Ministry of Education and Science. Investigation on the possibilities for control of proliferation of tumor cells through specific iRNA mollecules. Project leader: Prof. I. Kehayov

        3.       4/2006, National Scientific Program “GENOMICS”, Investigation on the plasticity of human mesenchymal stem cells.  Project leader: Prof. S. Kyurkchiev

        4.       L-1523/2005, Ministry of Education and Science. Clinical and experimental characterization of specific markers for the autoimmune disease of the internal year. Project leader: Prof. S. Lolov

        5.       L-1511/05, Ministry of Education and Science. Expression of low molecular mass stress proteins in human placenta under normal conditions and in pregnancy failure. Principal Investigator: Assoc. Prof. Dr. M. Stamenova.

        6.       L-1517/2005, Ministry of Education and Science. Investigation on the effect of reproductive steroid hormones in proliferation and differentiation of human stem cells. Project leader: Prof. S. Kyurkchiev

        7.       MUК 1406/2004, Ministry of Education and Science. Following the externalization of phosphatidylserin in cellular membrane thorugh monoclonal antibodies. Project leader: K. Ivanova – Todorova

        8.       MU-L–1401/04, Ministry of Education and Science. Identification of marker proteins for endometriosis in the peritoneal fluid of patients. Principal Investigator: Roumen Dimitrov.

        9.       NATOReintegrationgrant982763/2007-2010. MitoticexitregulatorynetworksinhumancellsandcancerdevelopmentPrincipal Investigator: IrinaAlexanderIMBIBIRPartner – DianaZasheva

        10.    BAS grant.Developmentoflaboratoryprotocolsforderivationofinducedpluripotentstemcells. Principal investigator: Milena Mourdjeva

        11.    BAS grantDevelopmentofxeno-freeconditionsforculturingofhumanembryonicstemcells (line BG01V). Principal investigatorTsvetelinaOreshkova

        12.    BAS grant.Studies on the endometriosis pathogenesis. Principal Investigator: Roumen Dimitrov.

        13.    BAS grant.Pregnancy and diabetes. Principal InvestigatorsKatiaTodorovaKameliyaPetkova

        • Scientific publications

          Scientific papers published during last 5 years.

          Papers in International peer-reviewed scientific journals

          R.T.Gergova, M.P.Slavova, V.I.Boev, M.S.Mourdjeva, L.K.Yotova, R.T.Georgieva-Nikolova    Comparative investigation of the feasibility of bacterial biofilms formation on the surface of the hybrid material UREASIL. Bulgarian Chemical Communications, 47, 2, 706-713, 2015.

          ISSN: 0324-1130IF: 0.349

           

          Elena Stoyanova, M. Mourdjeva, S. Kyurjchiev. Early selection of human fibroblast-derived induced pluripotent stem cells. Biotechnology & Biotechnological Equipment, 29, 5, 942-948, 2015.

          ISSN: 1310-2818IF:0.3

           

          Kyurkchiev D, E.Naydenov, K.Tumangelova-Yuzeir, E.Ivanova-Todorova, K.Belemezova, I.Bochev, K.Minkin, M.Mourdjeva, T.Velikova, S.Nachev, S.Kyurkchiev   Cells Isolated from Human Glioblastoma Multiforme Express Progesterone-Induced Blocking Factor (PIBF). Cellular and Molecular Neurobiology, 34, 1, 479-489, 2014.

          ISSN: 0272-4340 IF: 2.506

           

          K.Belemezova, I.Bochev, M.Mourdjeva, A.Shterev, S.Kyurkchiev   Effect of GNRH analogues ganirelix and triptorelin on human endometrial stromal cell decidualization in vitro. Compt.Rend.Acad.Bulg.Sci., 67, 1, 77-86, 2014.

          ISSN: 1310-1331IF: 0.284

           

          Sh.Pashova, K.Dobrev, A.Pashov   Regulatory properties of mouse transitional 1 B lymphocytes. Compt.Rend.Acad.Bulg.Sci., 67, 3, 361-366, 2014.

          ISSN: 1310-1331IF: 0.284

           

          A.Daskalova, Ch.s.r.Nathala, I.Bliznakova, E.Stoyanova, A.Zhelyazkova, T.Ganz, S.Lueftenegger, W.Husinsky   Controlling the porosity of collagen, gelatin and elastin biomaterials by ultrashort laser pulses. Applied Surface Sci., 292, 367-377, 2014.

          ISSN: 0169-4332IF: 2.711

           

          D. Kyurkchiev, I.Bochev, E.Ivanova-Todorova, M.Mourdjeva, Ts.Oreshkova, K.Belemezova, St.Kyurkchiev   Secretion of immunoregulatory cytokines by mesenchymal stem cells. World Journal of Stem Cells, V. 6, 5, 552-570, 2014.

          ISSN: 1948-0210

           

          V. Mantareva, A. Kril, I. Angelov, R. Dimitrov, D. Wohrle    Selective photodynamic therapy with galactopyranosyl Zn(II) phthalocyanines induced by preirradialion with UV and red lights. Journal of Porphyrins and Phthalocyanines, 17, 6-7, 529-539, 2013.

          ISSN: 1088-4246        IF: 1. 364

           

          P.Mladenov, D.Zasheva, D.Peshev, N.K.Christov, N.Rollamd, D.Djilianov, M.Tchobadjieva   Sub-cellular fractionation and gel-based proteomics of haberlea rhodopensis: A promising approach to open the black box of resurrection plants. Bulgarian Journal of Agricultural Science, 19, 2, 22-25. 2013.

          ISSN: 1310-0351         IF 0.189(2012)

           

          K.Todorova, M.Mincheff, S.Hayrabedyan, J.Mincheva, D.Zasheva, A.Kuzmanov, N.Femandez   Fundamental role of microRNAs in androgen-dependent male reproductive

          biology and prostate cancerogenesis. Am. J. Reprod. Immunol. 69, 2, 100-104, 2013.

          Print ISSN: 1046-7408, Online ISSN: 1600-0897. IF: 2.668

           

          S.Hayrabedyan, M.Mincheff, D.Zasheva, N.Manolova, K.Todorova   Autophagy signallings is differentially modulated by miR-204 in context of innate immunity induction.

          Comptes rendus de PAcademie bulgare des Sciences, V.66, No 1, 127-132, 2013.

          ISSN: 1310-1331. IF: 0.198

           

          N.Manolova, S.Hayrabedyan, K.Todorova, D.Zasheva, M.Mourdjeva, S.Kyurkchiev, M.Stamenova   Endometriosis peritoneal fluid factors involved in the alteration of

          decidualization process. Biotechnol.& Biotechnol.Eq., 27, 4, 3982-3986, 2013.

          ISSN: 1310-2818       IF: 0. 379

           

          S.Hayrabedyan, K.Todorova, D.Zasheva, D.Moyankova, D.Georgieva, J.Todorova, D.Djilianov   Haberlea Rhodopensis has potential as a new drug source based on its broad biological modalities. Biotechnol.& Biotechnol.Eq., 27, 1, 3553-3560, 2013.

          ISSN: 1310-2818       IF: 0. 379

           

          Manolova N., Hayrabedyan S., Todorova K., Zasheva D., Mourdjeva M., Kyurkchiev S., Stamenova M.   In search of factors in endometriosis peritoneal fluid that decreased

          decidualization process. Comptes rendus de I’Academie bulgare des Sciences, V.66, No 1,

          153-158,2013.

          ISSN: 1310-1331. IF: 0.198

           

          B.Antonov, I.Bochev, M.Mourdjeva, P.Kinov, L.Tzvetanov, I.Sheitanov, S.Kyurkchiev   Porous coated titanium implants do not inhibit mesenchimal stem cells proliferation and osteogenic differentiation. Biotechnol.& Biotechnol.Eq., 27, 6, 4290-4293, 2013.

          ISSN: 1310-2818        IF: 0.379

           

          T.Kurteva, E.Kinova, D.Somleva, N.Spasova, N.Poroyliev, T.Velikov, M.Mourdjeva, A.Goudev   The role of biomarkers high sensitivity CRP, soluble CD40, ligand and

          endothelial dysfunction in patients with acute coronary syndrome. Compt.Rendus Acad.Bulg.Sci., 66, 11, 1645-1652, 2013.

          ISSN: 1310-1331        IF: 0.198

           

          D.Somleva, E.Kinova, N.Spasova, T.Kourteva, M.Mourdjeva, S.Kyurkchiev, I.Kehayov, A.Goudev   The role of matrix metalloproteinases 2 and 9 in vascular and ventricular remodeling in patients with hearth failure with preserved ejection fraction. Compt.Rendus Acad.Bulg.Sci., 66, 2, 289-296, 2013.

          ISSN: 1310-1331        IF: 0.198

           

          I.Djumerska-Alexieva, Sh.Pashova, Tch.Vassilev, A.Pashov   The protective effect of modified intravenous immunoglobulin in LPS sepsis model is associated with an increased IRA В cells response. Autoimmunity Reviews, 12, 653-656, 2013.

          ISSN:   1568-9972      IF: 7.095

           

          E.Ivanova-Todorova, I.Bochev, R.Dimitrov, K.Belemezova, M.Mourdjeva, S.Kyurkchiev, P.Kinov, I.Altankova, D.Kyurkchiev   Conditioned Medium from Adipose Tissue-Derived Mesenchymal Stem Cells Induces CD4+FOXP3+Cells and Increases IL-10 Secretion. Journal of Biomedicine and Biotechnology, ID 29167, 2012.

          ISSN (electronic): 1110-7251.   IF: 2.436

           

          R.Dimitrov, G.Georgiev, P.Todorov, Y.Dimitrov, R.Konakchieva      Membrane Melatonin Receptor Type MT1 Expression in Human Ejaculated Spermatozoa. Compt.Rendus Acad. Bulg. Sci., 65, 7, 947-952, 2012.

          ISSN 1310-1331. IF : 0.210

           

          E.Ivanova-Todorova, I.Bochev, R.Dimitrov, K.Belemezova, M.Mourdjeva, S.Kyurkchiev, P.Kinov, I.Altankova, D.Kyurkchiev   Conditioned Medium from Adipose Tissue-Derived Mesenchymal Stem Cells Induces CD4+FOXP3+Cells and Increases IL-10 Secretion. Journal of Biomedicine and Biotechnology, ID 29167, 2012.

          ISSN (electronic): 1110-7251.   IF: 2.436

           

          R.Dimitrov, G.Georgiev, P.Todorov, Y.Dimitrov, R.Konakchieva      Membrane Melatonin Receptor Type MT1 Expression in Human Ejaculated Spermatozoa. Compt.Rendus Acad. Bulg. Sci., 65, 7, 947-952, 2012.

          ISSN 1310-1331. IF : 0.210

           

          I.Bochev, M.Mourdjeva, S.Kyurkchiev, I.Kehayov   Production and characterization of polyclonal antibodies against human keratinocyte membrane protein fraction. Compt.Rendus Acad.Bulg.Sci., 65, 11, 1575-1584, 2012.

          ISSN 1310-1331. IF: 0.210

           

          Ts.Oreshkova, R.Dimitrov, M.Mourdjeva   A cross-talk of decidual stromal cells, trophoblast, and immune cells: A prerequisite for the success of pregnancy. A.J.R.I., 68, 366-373, 2012.

          ISSN: 1046-7408. IF: 3.050

           

          S.Kyurkchiev, F.Gandolfi, S.Hayrabedyan, T.A.L.Brevini, R.Dimitrov, J.S.Fitzgerald, A.Jabeen, M.Mourdjeva, S.M.Photini, P.Spencer, N.Fernandez, U.R.Markert    Stem cells in the reproductive system. A.J.R.I., 67, 6, 445–462, 2012.

          ISSN: 1046-7408, Online ISSN: 1600-0897. IF: 3.050

           

          I.Sainova, I.Vavrek, Sh.Pashova, K.Lazov, S.Manchev, V.Pavlova, E.Nikolova, K/Miteva, T.Daneva  (2012) Experimental human and animal models for balanced activity of oncogenes and tumor-suppressor genes and their protein products. Instanci Journal of Medical Sciences and Clinical Research, V.2, 1, 15-24, 2012.

          ISSN: 2277-6966

           

          V.Mantareva, V.Kussovski, I.Angelov,  D.Wöhrle, R.Dimitrov, E.Popova, S.Dimitrov   Non-aggregated Ga(III)-phthalocyanines in the photodynamic inactivation of planktonic and biofilm cultures of pathogenic microorganisms. Photochemical & Photobiological Sciences, V.10, 1, 91-102, 2011.

          ISSN: 1474-905X   IF – 2.505

           

          V.Mantareva, I.Angelov, V.Kussovski, R.Dimitrov, L.Lapok, D.Wöhrle    Photodynamic efficacy of water-soluble Si(IV) and Ge(IV) phthalocyanines towards Candida albicans planktonic and biofilm cultures. European Journal of Medicinal Chemistry, V. 46, 9, 4430-4440, 2011.

          ISSN: 0023-5234IF – 3.356

           

          Kyurkchiev D., E.Ivanova-Todorova, M.Mоurdjeva, S.Kyurkchiev   Immunoregulation by Progesterone: Effects on Immune Cells and Mesenchymal Stem Cells. Advances in neuroimmune biology, V.1, No 2, 105- 123, 2011.

          ISSN 1878-9498

          Papers in National (Bulgarian) scientific journals

           

          М.Мурджева, Цв.Орешкова, Р.Димитров, Д.Зашева, Н.Манолова, Е.Стоянова, К.Петкова, М.Костадинова   Молекулярна имунология – изцледвания и развитие. Списание на БАН, 127, 1, 22-26, 2014.

          ISSN: 0007-3989

           

          Калоянова С, Минковска С, Винкетова К, Тропчева Р, Данова C.   Флуоресцентно маркиране на протеини – основни подходи и приложения. Българско списание за химия, 2, 3, 77-91, 2013.

          ISSN 1314-6017 (online), ISSN 1314-5894 (print)

           

          К.Тумангелова-Юзеир, Е.Найденов, Е.Иванова-Тодорова, Ц.Младенова, С.Начев, М.Мурджева, Д.Кюркчиев   Клетки, изолирани и култивирани от глиобластома мултиформе, имат прилики с мезенхимни стволови клетки. Български Медицински журнал, VII, 3, 56-60, 2013.

          ISSN: 1312-2193

           

          V.Nikolova, I.Chakarova, R.Zhivkova, M.Markova, R.Dimitrov, S.Delimitreva   Comparison of in vitro matured oocytes from two inbred mouse  strains and their F1 hybrids. Embryology, 7, 1, 10-14. 2012

          ISSN: 1312-7349

           

          V.Nikolova, I.Chakarova, R.Zhivkova, M.Markova, R.Dimitrov, S.Delimitreva   Comparison of in vitro matured oocytes from two inbred mouse  strains and their F1 hybrids. Embryology, 7, 1, 10-14. 2012

          ISSN: 1312-7349

           

          N.Manolova, D.Zasheva, M.Stamenova   Immunobiology of endometriosis. Acta Medica Bulgarica, 38, 1, 38-50, 2011.

          ISSN: 0324-1750

           

          Popular Science, Current Affairs publications and Educational publications
          Books and brochures

          V.Mantareva, A.Kril, I.Angelov, R.Dimitrov, E.Borisova, L.Avramov   Effects of the position of Galactose units to Zn(II) phthalocyanine on the uptake and photodynamic activity towards breast cancer cells. Proc. of SPIE Vol. 8427 Biophotonics: Photonic Solutions for Better Health Care III, 2012.
          ISBN: 9780819491190

           

          D.Kyurkchiev, E.Ivanova-Todorova, I.Bochev, M.Mourdjeva, S.Kyurkchiev   Differences between adipose tissue-derived mesenchymal stem cells and bone marrow-derived mesenchymal stem cells as regulators of the immune response. Stem Cells and Cancer Stem Cells, Volume 10. Springer Science+Business Media Dordrecht, 2013.

          ISBN: 978-94-007-6261-9 (Print) 978-94-007-6262-6 (Online)

           

          V.Mantareva, I.Angelov, D.Wöhrle, V.Dogandjiska, R.Dimitrov, V.Kussovski    Water-soluble phthalocyanine complexes of Ga(III) and In(III) in the photodynamic inactivation of pathogenic fungus. Proceedings of SPIE – The International Society for Optical Engineering, V. 7747 – 16th International School on Quantum Electronics: Laser Physics and Applications, Article number 774712, 2011.
          ISBN: 9780819482372

          Previous publications

          Papers in International peer-reviewed scientific journals

          1. S.Kyurkchiev, A.Shterev, R.Dimitrov. Assessment of presence and characteristics of multipotent stromal cells in human endometrium and decidua. Reproductive BioMedicine Online 20 (3), pp. 305-313. 2010, ISSN (printed): 1472-6483. ISSN (electronic): 1472-6491. IF – 2.380.
          2. D.Kyurkchiev, E.Ivanova-Todorova, S. Kyurkchiev. New target cells of the immunomodulatory effects of progesterone. Reproductive BioMedicine Online 21 (3), 304– 311. 2010, ISSN (printed): 1472-6483. ISSN (electronic): 1472-6491. IF – 2.380.
          3. Dimitrov, R., Kyurkchiev, D., Timeva, T., Yunakova, M., Stamenova, M., Shterev, A., Kyurkchiev, S. First-trimester human decidua contains a population of mesenchymal stem cells. Fertility and Sterility,93(1),pp.210-219. 2010. ISSN (printed): 0015-0282, ISSN (electronic): 1556-5653. Impact factor 3.970.
          4. Oreshkova, T., Stoyanova, E., Mourdjeva, M., Kyurkchiev, S. Human adipose tissue-derived mesenchymal stem cells support the growth and plasticity of human embryonic stem cells (BG01V cell line). Comptes Rendus de L’Academie Bulgare des Sciences, 63 (10), pp.1477-1484. 2010, ISSN 1310-1331. IF – 0.204.
          5. Kestendjieva, S., Popova, Z., Cvetkova, G., Bochev, I., Kehayov, I., Kyurkchiev, S., Mourdjeva, M. Different Effects of Conditioned Medium Samples from Mesenchymal Stem Cells (CM-MSC) Isolated from Different Sources. Comptes Rendus de L’Academie Bulgare des Sciences, 63 (1), pp 97-105. 2010, ISSN 1310-1331. IF – 0.204.
          6. Mantareva V., Kussovski V.,  Angelov I.,  W¨ohrle D., Dimitrov R., Popovae E., Dimitrov S. Non-aggregated Ga(III)-phthalocyanines in the photodynamic inactivation of planktonic and biofilm cultures of pathogenic microorganisms. Photochemical & Photobiological Sciences available online – DOI: 10.1039/b9pp00154a.
          7. E.Ivanova-Todorova, M.Mourdjeva, D.Kyurkchiev, I.Bochev, E.Stoyanova, R.Dimitrov, T.Timeva, M.Yunakova, D.Bukarev, A.Shterev, P.Tivchev, S.Kyurkchiev. HLA-G Expression Is Up-Regulated by Progesterone in Mesenchymal Stem Cells. Am J Reprod Immunol; 62: 25–33. 2009. ISSN: 1046-7408. IF 2.172.
          8. E.Ivanova-Todorova, I.Bochev, M.Mourdjeva, R.Dimitrov, D.Bukarev, S. Kyurkchiev, P.Tivchev, I.Altunkova, D. Kyurkchiev. Adipose tissue-derived mesenchymal stem cells are more potent suppressors of dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cells. Immunology Letters 126, 37–42. 2009. ISSN: 0165-2478. Impact Factor: 2.906.
          9.  M.Mourdjeva, A.Mandinova, S.Kyurkchiev, I.Kehayov. Experimental data for inhibition of the expression of surviving by small interfering RNA molecules (siRNAs). C.r.Acad Bulg Sci, ,Tome 62, No 5, 647-652. 2009. ISSN 1310-1331. IF – 0.204.
          10.  S. Kestendjieva, Z. Popova, I. Bochev, I. Kehayov, S. Kyurkchiev, M. Mourdjeva. Mesenchymal stem cells conditioned medium promotes the diferentiation of umbilical cord blood isolated endothelial progenitor cells. C.r.Acad Bulg Sci, , 62, 6, 739-744. 2009. ISSN 1310-1331. IF – 0.204
          11. Zasheva D, Dimitrov R, Stamenova M, Kyurkchiev D. A comparison of stromal cells isolated from human endometrium and endosalpinx Compt. Rend. Bulg. Sci;62 (7): 839-848. 2009. ISSN 1310-1331. IF – 0.204.
          12. Mourdjeva, M., Ivanova-Todorova, E., Kyurkchiev, D., Bochev, I., Stoyanova, E., Dimitrov, R., Kyurkchiev, S. Progesterone enhances the HLA-G expression in mesenchymal stem cells. Comptes Rendus de L’Academie Bulgare des Sciences,62(12), pp.1559-1566. 2009. ISSN 1310-1331. IF – 0.204.
          13. .Ivanova-Todorova, E., Kyurkchiev, D., Mourdjeva, M., Dimitrov, R., Stoyanova, E., Timeva, T., Yunakova, M., Shterev, A., Kyurkchiev, S. Pre-decidual multipotent stromal cells (PreDMSc) constitutively express progesterone induced blocking factor (PIBF). Comptes Rendus de L’Academie Bulgare des Sciences, 62 (12), pp. 1567-1570. 2009. ISSN 1310-1331. IF – 0.204.
          14. M. Draganova-Filipova, M. Mourdjeva, Z. Popova, E. Peycheva, G. Miloshev, V. Sarafian. Propolis Induced Apoptosis In Mc Coy-Plovdiv Cells. Biotechnol. & biotechnol. Eq. 23/2009/se special edition/on-line, 635-638, 2009. ISSN: 1310-2818. IF 0,291.
          15.  I.Bochev, S.Kyurkchiev. Immunomodulatory effects of human bone marrow or adipose tissue derived mesenchymal stem cells on T-helper cell cytokine production in vitro. Comptes Rendus de L’Academie Bulgare des Sciences 62 (12), pp. 1553-1558. 2009. ISSN 1310-1331. IF – 0.204.
          16. K. Danailov, P. Rashev, D. Zasheva, M. Mollova, Immunological characterization of sperm specific antigen with potential fusogenic activity in fertilization. C.r. Acad. Sci. Bulg, t.62, N207, 2009, ISSN 1310-1331.
          17. Klimentina Demirevska, Diana Zasheva, Rumen Dimitrov, Ljudmila Simova-Stoilova, Maria Stamenova, Urs Feller. Drought stress and Rubisco large subunit changes in wheat leaves after 2D-electrophoretic analysis. A comparison with SDS-PAGE analysis. Acta Physiologie Plantarum, 31, 1129-1138, (2009), IF – 0,807, 0137-5881 (Print), 0137-5881 (Linking).
          18. Bochev, I., G. Elmadjian, D. Kyurkchiev, L. Tzvetanov, I. Altankova, P. Tivchev, S. Kyurkchiev. Mesenchymal stem cells from human bone marrow or adipose tissue differently modulate mitogen-stimulated B-cell immunoglobulin production in vitrо. Cell Biol Internatl., 32, 384 – 393. 2008. ISSN: 1065-6995. IF – 1.619.
          19.  Ivanova-Todorova, E., D. S. Kyurkchiev, A. Nalbanski, T. Timeva, A. Shterev, S. D. Kyurkchiev. Production and characterization of a novel monoclonal antibody against progesterone induced blocking factor (PIBF) – J. Reprod Immunol., 78, 94–101, 2008. ISSN: 0165-0378. 2.778.
          20. Dimitrov, R., T. Timeva, D. Kyurkchiev, M. Stamenova, A. Shterev, P. Kostova, V. Zlatkov, I. Kehayov, S. Kyurkchiev. Characterization of clonogenic stromal cells isolated from human endometrium – Reproduction, 135, 551–558, 2008. ISSN: 0268-1161. IF – 3.773.
          21. Kestendjieva, S., D. Kyurkchiev, G. Tsvetkova, T. Mehandjiev, A. Dimitrov, A. Nikolov, S. Kyurkchiev. Characterization of mesenchymal stem cells isolated from human umbilical cord – Cell Biol Internatl., 32, 724 – 732, 2008. ISSN: 1065-6995. IF – 1.619.
          22. Koleva, К., E. Ivanova, E. Kinova, N. Zlatareva, I. Kehayov, S. Kyurkchiev, A. Goudev. Circulating oxidized low-density lipoproteins and antibodies against oxidized low-density lipoproteins in patients with degenerative aortic valve stenosis – C. r. Acad. bulg Sci, 61(8), 1087-1092, 2008. ISSN 1310-1331. IF – 0.152.
          23. Hayrabedyan, S., S. Kyurkchiev, I. Kehayov. Calcium-binding protein S100A13 is overexpressed in endometriosis – C. r. Acad. bulg Sci, 2008, 61(2), 281-288. ISSN 1310-1331. IF – 0.152.
          24. Ivanova – Todorova, E., D. Kyurkchiev , Tz. Mehandjiev, T. Chernev, S. Kyurkchiev. Influence of progesterone on asymmetric antibodies in vitro.  C. r. Acad. bulg Sci 61 (11), pp. 1475-1480. 2008. ISSN 1310-1331. IF – 0.152.
          25. Todorova K, Shamov T, Hayrabedyan, Kuzmanov A, Kyurkchiev S, Kehayov I. Quantitative evaluation of angiogenesis in glioblastoma with CD105., Compt. Rend. Bulg. Acad. Sci., 60 /5/, 575-578, 2007. ISSN 1310-1331. IF – 0.152.
          26. Kyurkchiev D., E. Ivanova-Todorova, S. Hayrabedyan, I. Altankova, S. Kyurkchiev. Female sex steroid hormones modify some regulatory properties of monocyte-derived dendritic cells. Amer. J. Reprod. Immunol., 58, 425–433, 2007. ISSN: 1046-7408. IF 2.13.
          27. Hayrabedyan S., S. Kyurkchiev, I. Kehayov. FGF-1 and S100A13 possibly contribute to angiogenesis in endometriosis. J. Reprod. Immunol., 67, /1-2/, 87-101, 2006. ISSN: 0165-0378 . IF 2,536.
          28. Mourdjeva M., Z. Popova, D. Kyurkchiev, K. Kontinopoulou, I. Altankova, I. Kehayov, S. Kyurkchiev. Progesterone-modulated Phosohatidylserine Externalization in Apoptosis and Activation of Jurkat Cells. AJRI, 56, 1-9, 2006. ISSN 1046-7408. IF 1,743.
          29. Hayrabedyan S., S. Kyurkchiev, I. Kehayov. Endoglin (cd105) and S100A13 as markers of active angiogenesis in endometriosis. Reprod. Biol., 5, /1/, 51-67, 2005. ISSN 0006-3363. IF – 3.583.
          30. Todorova K., S. Zoubak, M. Mincheff, S. Kyurkchiev. Biochemical Nature and mapping of PSMA epitopes recognized by human antibodies induced after immunization with gene-based vaccines. Anticancer research, 25, 4727-4732, 2005. ISSN 0250-7005. IF – 1.604.
          31. Todorova K., I. Ignatova, S. Tchakarov, I. Altankova, S. Zoubak, S. Kyurkchiev, M. Mincheff. Humoral immune response in prostate cancer patients after immunization with gene-based vaccines that encode for a protein that is proteasomally degraded. Cancer Immunity, 5, 1-9, 2005.ISSN 1424-9634.
          32. Mourdjeva M., D. Kyurkchiev, A. Mandinova, I. Altankova, I. Kehayov, S. Kyurkchiev. Dynamics of membrane translocation of phosphatidylserine during apoptosis detected by a monoclonal antibody. Apoptosis, 10, 209-217, 2005.ISSN 1360-8185. IF – 4.497.
          33. Ivanova E., D. Kyurkchiev, I. Altankova, J. Dimitrov, E. Binakova, S. Kyurkchiev. CD83+ monocyte-derived dendritic cells are present in human decidua and progesterone induces their differentiation in vitro. Amer. J. Reprod. Immunol., 53, 1-7, 2005. ISSN 1046-7408. IF – 1.416.
          34. D. Zasheva, I. Alexandar, Protein release in a Saccharomyces cerevisiae mutant does not depend on mitochondrial genome integrity and function. Microbiological Research, 76 (10), 2005, IF 0,862, ISSN 0944-5013.

           

          Papers in National (Bulgarian) scientific journals

          1. Румен Димитров, Атанас Щерев, Станимир Кюркчиев. Мултипотентни сволови клетки в човешкия ендометриум и децидуа. Репродуктивно здраве, 17, 34-48, (2010), ISSN: 1312-6180.
          2. М.Мурджева, Е.Стоянова, С.Кюркчиев. Индуцирани плурипотентни стволови клетки. Съвременна медицина, 2009.
          3. И.Кехайов, С.Кюркчиев. Стволови клетки и злокачествени заболявания. Съвременна медицина, 2009.
          4. Бочев, И., Д. Кюркчиев, Л. Цветанов, И. Алтънкова, П. Тивчев, С. Кюркчиев. Сравнително изследване върху мезенхимни стволови клетки, изолирани от мастна тъкан. Съвр. медицина, 2008, 1, 29-36.
          5. Кестенджиева, С., Д. Кюркчиев, Г. Цветкова, Ц. Механджиев, А. Димитров, А. Николов, С. Кюркчиев. Изследване на потенциала за диференциация на мезенхимни стволови клетки, изолирани от стената на пъпна вена. Съвр. медицина, 2008, 1, 20 -27.
          6. Налбански, А., Д. Кюркчиев. Използването на някои биохимични маркери при диагностиката на гениталната ендометриоза.  Акушерство и гинекология, 2008, 4, 19 – 22.
          7. Кюркчиев, Д., А. Налбански. Ангиогенеза и апоптоза при ендометриозната болест. Съвременна медицина, 2008, 4, 64-69.
          8. Налбански, A., Д. Кюркчиев. Имунокомпетентни клетки в патогенезата на едндометриозата. Акушерство и гинекология, 2008
          9. Тодорова К.,  К. Петкова. Актуални аспекти в етиологията, патогенезата и лечението  на гестационния захарен диабет. Medinfo. 8, 4,23-28, (2008) ISSN 1313-2466
          10. Петкова К., К. Тодорова–Ананиева, М. Стаменова. Протеини на топлинния стрес. Мед. Преглед, 44, 1, 32-43, (2008), ISSN 1313-9134
          11. Тодорова К.,  К. Петкова, М Стаменова. Актуални аспекти в етиологията на захарния диабет.  Български медицински журнал. (2008), ISSN 1313-1516
          12. Зашева Диана, Румен Димитров, Мария Стаменова. Ендометриоза и роля на интегрините в патогенезата на ендометриоза. Акушерство и гинекология, том 46, бр.5, 37-48, (2007), ISSN 0324-0959.
          13. Катя Тодорова, Камелия Петкова, Мария Стаменова. Протеини на топлинния шок в репродукцията. Акушерство и гинекология,8, 46, 16-22, (2007), ISSN 0324-0959
          14. Kestendjieva S, Mourdjeva M, Kyukchiev D, Mehandjiev Tz, Nickolova A,    Kyurkchiev S. Isolation and characterization of umbilical vein mesenchymal stem cells. Compt. Rend. Bulg. Acad. Sci., 59, 775-780, 2006.
          15. Bochev I, Kyurkchiev D, Tivchev P, Tzvetanov L, Kyurkchiev S. Isolation and immunomodulatory activity of bone marrow mesenchymal stem cells. Compt. Rend. Bulg. Acad. Sci., 59, 775-780, 2006.
          16. Dimitrov R, Timeva T, Stameneova M, Kyurkchiev D, Shterev A, Kyurkchiev S Effect of peritoneal fluid from patients with endometriosis on morphological characterisation of endosalpinx stromal cell culture. Compt. Rend. Bulg. Acad. Sci., 59, 775-780, 2006.
          17. Hayrabedyan S., Kyurkchiev S., Kehayov I. Evaluation of IL-1α Expression in Endometriotic Lesions Using Quantitative Immunohistochemistry Approach. Compt. Rend. Bulg. Acad. Sci., 59, /2/, 229, 2006.
          18. М. Мурджева. Регулация и значение на апоптозата при стволови клетки. Pепродуктивно здраве, 11, 18-25; 2005
          19.  Z. Popova, M. Mourdjeva, S. Kyurkchiev, I. Kehavyov. Internalization Of Exposed Phosphatidylserine After Treatment With Low Doses Of H2O2. Comptes rendus de l’Academie bulgare des Sciences, Vol. 58, N 11, 1319-1324, 2005.
          20. С. Кюркчиев. Стволови клетки – класификация, определения. Репрод.Здраве, 11, 3 – 10, 2005.

          Scientific publications since 2005

          1. S.Kyurkchiev, A.Shterev, R.Dimitrov. Assessment of presence and characteristics of multipotent stromal cells in human endometrium and decidua. Reproductive BioMedicine Online 20 (3), pp. 305-313. 2010, ISSN (printed): 1472-6483. ISSN (electronic): 1472-6491. IF – 2.380.
          2. D.Kyurkchiev, E.Ivanova-Todorova, S. Kyurkchiev. New target cells of the immunomodulatory effects of progesterone. Reproductive BioMedicine Online 21 (3), 304– 311. 2010, ISSN (printed): 1472-6483. ISSN (electronic): 1472-6491. IF – 2.380.
          3. Dimitrov, R., Kyurkchiev, D., Timeva, T., Yunakova, M., Stamenova, M., Shterev, A., Kyurkchiev, S. First-trimester human decidua contains a population of mesenchymal stem cells. Fertility and Sterility,93(1),pp.210-219. 2010. ISSN (printed): 0015-0282, ISSN (electronic): 1556-5653. Impact factor 3.970.
          4. Oreshkova, T., Stoyanova, E., Mourdjeva, M., Kyurkchiev, S. Human adipose tissue-derived mesenchymal stem cells support the growth and plasticity of human embryonic stem cells (BG01V cell line). Comptes Rendus de L’Academie Bulgare des Sciences, 63 (10), pp.1477-1484. 2010, ISSN 1310-1331. IF – 0.204.
          5. Kestendjieva, S., Popova, Z., Cvetkova, G., Bochev, I., Kehayov, I., Kyurkchiev, S., Mourdjeva, M. Different Effects of Conditioned Medium Samples from Mesenchymal Stem Cells (CM-MSC) Isolated from Different Sources. Comptes Rendus de L’Academie Bulgare des Sciences, 63 (1), pp 97-105. 2010, ISSN 1310-1331. IF – 0.204.
          6. Mantareva V., Kussovski V., Angelov I., W¨ohrle D., Dimitrov R., Popovae E., Dimitrov S. Non-aggregated Ga(III)-phthalocyanines in the photodynamic inactivation of planktonic and biofilm cultures of pathogenic microorganisms. Photochemical & Photobiological Sciences available online – DOI: 10.1039/b9pp00154a.
          7. E. Ivanova-Todorova, M.Mourdjeva, D.Kyurkchiev, I.Bochev, E.Stoyanova, R.Dimitrov, T.Timeva, M.Yunakova, D.Bukarev, A.Shterev, P.Tivchev, S.Kyurkchiev. HLA-G Expression Is Up-Regulated by Progesterone in Mesenchymal Stem Cells. Am J Reprod Immunol; 62: 25–33. 2009. ISSN: 1046-7408. IF 2.172.
          8. E. Ivanova-Todorova, I.Bochev, M.Mourdjeva, R.Dimitrov, D.Bukarev, S. Kyurkchiev, P.Tivchev, I.Altunkova, D. Kyurkchiev. Adipose tissue-derived mesenchymal stem cells are more potent suppressors of dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cells. Immunology Letters 126, 37–42. 2009. ISSN: 0165-2478. Impact Factor: 2.906.
          9. M. Mourdjeva, A.Mandinova, S.Kyurkchiev, I.Kehayov. Experimental data for inhibition of the expression of surviving by small interfering RNA molecules (siRNAs). C.r.Acad Bulg Sci, ,Tome 62, No 5, 647-652. 2009. ISSN 1310-1331. IF – 0.204.
          10. S. Kestendjieva, Z. Popova, I. Bochev, I. Kehayov, S. Kyurkchiev, M. Mourdjeva. Mesenchymal stem cells conditioned medium promotes the diferentiation of umbilical cord blood isolated endothelial progenitor cells. C.r.Acad Bulg Sci, , 62, 6, 739-744. 2009. ISSN 1310-1331. IF – 0.204
          11. Zasheva D, Dimitrov R, Stamenova M, Kyurkchiev D. A comparison of stromal cells isolated from human endometrium and endosalpinx Compt. Rend. Bulg. Sci;62 (7): 839-848. 2009. ISSN 1310-1331. IF – 0.204.
          12. Mourdjeva, M., Ivanova-Todorova, E., Kyurkchiev, D., Bochev, I., Stoyanova, E., Dimitrov, R., Kyurkchiev, S. Progesterone enhances the HLA-G expression in mesenchymal stem cells. Comptes Rendus de L’Academie Bulgare des Sciences,62(12), pp.1559-1566. 2009. ISSN 1310-1331. IF – 0.204.
          13. Ivanova-Todorova, E., Kyurkchiev, D., Mourdjeva, M., Dimitrov, R., Stoyanova, E., Timeva, T., Yunakova, M., Shterev, A., Kyurkchiev, S. Pre-decidual multipotent stromal cells (PreDMSc) constitutively express progesterone induced blocking factor (PIBF). Comptes Rendus de L’Academie Bulgare des Sciences, 62 (12), pp. 1567-1570. 2009. ISSN 1310-1331. IF – 0.204.
          14. M. Draganova-Filipova, M. Mourdjeva, Z. Popova, E. Peycheva, G. Miloshev, V. Sarafian. Propolis Induced Apoptosis In Mc Coy-Plovdiv Cells. Biotechnol. & biotechnol. Eq. 23/2009/se special edition/on-line, 635-638, 2009. ISSN: 1310-2818. IF 0,291.
          15. I. Bochev, S.Kyurkchiev. Immunomodulatory effects of human bone marrow or adipose tissue derived mesenchymal stem cells on T-helper cell cytokine production in vitro. Comptes Rendus de L’Academie Bulgare des Sciences 62 (12), pp. 1553-1558. 2009. ISSN 1310-1331. IF – 0.204.
          16. K. Danailov, P. Rashev, D. Zasheva, M. Mollova, Immunological characterization of sperm specific antigen with potential fusogenic activity in fertilization. C.r. Acad. Sci. Bulg, t.62, N207, 2009, ISSN 1310-1331.
          17. Klimentina Demirevska, Diana Zasheva, Rumen Dimitrov, Ljudmila Simova-Stoilova, Maria Stamenova, Urs Feller. Drought stress and Rubisco large subunit changes in wheat leaves after 2D-electrophoretic analysis. A comparison with SDS-PAGE analysis. Acta Physiologie Plantarum, 31, 1129-1138, (2009), IF – 0,807, 0137-5881 (Print), 0137-5881 (Linking).
          18. Bochev, I., G. Elmadjian, D. Kyurkchiev, L. Tzvetanov, I. Altankova, P. Tivchev, S. Kyurkchiev. Mesenchymal stem cells from human bone marrow or adipose tissue differently modulate mitogen-stimulated B-cell immunoglobulin production in vitrо. Cell Biol Internatl., 32, 384 – 393. 2008. ISSN: 1065-6995. IF – 1.619.
          19. Ivanova-Todorova, E., D. S. Kyurkchiev, A. Nalbanski, T. Timeva, A. Shterev, S. D. Kyurkchiev. Production and characterization of a novel monoclonal antibody against progesterone induced blocking factor (PIBF) – J. Reprod Immunol., 78, 94–101, 2008. ISSN: 0165-0378. 2.778.
          20. Dimitrov, R., T. Timeva, D. Kyurkchiev, M. Stamenova, A. Shterev, P. Kostova, V. Zlatkov, I. Kehayov, S. Kyurkchiev. Characterization of clonogenic stromal cells isolated from human endometrium – Reproduction, 135, 551–558, 2008. ISSN: 0268-1161. IF – 3.773.
          21. Kestendjieva, S., D. Kyurkchiev, G. Tsvetkova, T. Mehandjiev, A. Dimitrov, A. Nikolov, S. Kyurkchiev. Characterization of mesenchymal stem cells isolated from human umbilical cord – Cell Biol Internatl., 32, 724 – 732, 2008. ISSN: 1065-6995. IF – 1.619.
          22. Koleva, К., E. Ivanova, E. Kinova, N. Zlatareva, I. Kehayov, S. Kyurkchiev, A. Goudev. Circulating oxidized low-density lipoproteins and antibodies against oxidized low-density lipoproteins in patients with degenerative aortic valve stenosis – C. r. Acad. bulg Sci, 61(8), 1087-1092, 2008. ISSN 1310-1331. IF – 0.152.
          23. Hayrabedyan, S., S. Kyurkchiev, I. Kehayov. Calcium-binding protein S100A13 is overexpressed in endometriosis – C. r. Acad. bulg Sci, 2008, 61(2), 281-288. ISSN 1310-1331. IF – 0.152.
          24. Ivanova – Todorova, E., D. Kyurkchiev , Tz. Mehandjiev, T. Chernev, S. Kyurkchiev. Influence of progesterone on asymmetric antibodies in vitro. C. r. Acad. bulg Sci 61 (11), pp. 1475-1480. 2008. ISSN 1310-1331. IF – 0.152.
          25. Todorova K, Shamov T, Hayrabedyan, Kuzmanov A, Kyurkchiev S, Kehayov I. Quantitative evaluation of angiogenesis in glioblastoma with CD105., Compt. Rend. Bulg. Acad. Sci., 60 /5/, 575-578, 2007. ISSN 1310-1331. IF – 0.152.
          26. Kyurkchiev D., E. Ivanova-Todorova, S. Hayrabedyan, I. Altankova, S. Kyurkchiev. Female sex steroid hormones modify some regulatory properties of monocyte-derived dendritic cells. Amer. J. Reprod. Immunol., 58, 425–433, 2007. ISSN: 1046-7408. IF 2.13.
          27. Hayrabedyan S., S. Kyurkchiev, I. Kehayov. FGF-1 and S100A13 possibly contribute to angiogenesis in endometriosis. J. Reprod. Immunol., 67, /1-2/, 87-101, 2006. ISSN: 0165-0378 . IF 2,536.
          28. Mourdjeva M., Z. Popova, D. Kyurkchiev, K. Kontinopoulou, I. Altankova, I. Kehayov, S. Kyurkchiev. Progesterone-modulated Phosohatidylserine Externalization in Apoptosis and Activation of Jurkat Cells. AJRI, 56, 1-9, 2006. ISSN 1046-7408. IF 1,743.
          29. Hayrabedyan S., S. Kyurkchiev, I. Kehayov. Endoglin (cd105) and S100A13 as markers of active angiogenesis in endometriosis. Reprod. Biol., 5, /1/, 51-67, 2005. ISSN 0006-3363. IF – 3.583.
          30. Todorova K., S. Zoubak, M. Mincheff, S. Kyurkchiev. Biochemical Nature and mapping of PSMA epitopes recognized by human antibodies induced after immunization with gene-based vaccines. Anticancer research, 25, 4727-4732, 2005. ISSN 0250-7005. IF – 1.604.
          31. Todorova K., I. Ignatova, S. Tchakarov, I. Altankova, S. Zoubak, S. Kyurkchiev, M. Mincheff. Humoral immune response in prostate cancer patients after immunization with gene-based vaccines that encode for a protein that is proteasomally degraded. Cancer Immunity, 5, 1-9, 2005.ISSN 1424-9634.
          32. Mourdjeva M., D. Kyurkchiev, A. Mandinova, I. Altankova, I. Kehayov, S. Kyurkchiev. Dynamics of membrane translocation of phosphatidylserine during apoptosis detected by a monoclonal antibody. Apoptosis, 10, 209-217, 2005.ISSN 1360-8185. IF – 4.497.
          33. Ivanova E., D. Kyurkchiev, I. Altankova, J. Dimitrov, E. Binakova, S. Kyurkchiev. CD83+ monocyte-derived dendritic cells are present in human decidua and progesterone induces their differentiation in vitro. Amer. J. Reprod. Immunol., 53, 1-7, 2005. ISSN 1046-7408. IF – 1.416.
          34. D. Zasheva, I. Alexandar, Protein release in a Saccharomyces cerevisiae mutant does not depend on mitochondrial genome integrity and function. Microbiological Research, 76 (10), 2005, IF 0,862, ISSN 0944-5013.

          Scientific publications in Bulgarian journals

          35. Румен Димитров, Атанас Щерев, Станимир Кюркчиев. Мултипотентни сволови клетки в човешкия ендометриум и децидуа. Репродуктивно здраве, 17, 34-48, (2010), ISSN: 1312-6180.
          36. М.Мурджева, Е.Стоянова, С.Кюркчиев. Индуцирани плурипотентни стволови клетки. Съвременна медицина, 2009.
          37. И.Кехайов, С.Кюркчиев. Стволови клетки и злокачествени заболявания. Съвременна медицина, 2009.
          38. Бочев, И., Д. Кюркчиев, Л. Цветанов, И. Алтънкова, П. Тивчев, С. Кюркчиев. Сравнително изследване върху мезенхимни стволови клетки, изолирани от мастна тъкан. Съвр. медицина, 2008, 1, 29-36.
          39. Кестенджиева, С., Д. Кюркчиев, Г. Цветкова, Ц. Механджиев, А. Димитров, А. Николов, С. Кюркчиев. Изследване на потенциала за диференциация на мезенхимни стволови клетки, изолирани от стената на пъпна вена. Съвр. медицина, 2008, 1, 20 -27.
          40. Налбански, А., Д. Кюркчиев. Използването на някои биохимични маркери при диагностиката на гениталната ендометриоза. Акушерство и гинекология, 2008, 4, 19 – 22.
          41. Кюркчиев, Д., А. Налбански. Ангиогенеза и апоптоза при ендометриозната болест. Съвременна медицина, 2008, 4, 64-69.
          42. Налбански, A., Д. Кюркчиев. Имунокомпетентни клетки в патогенезата на едндометриозата. Акушерство и гинекология, 2008
          43. Тодорова К., К. Петкова. Актуални аспекти в етиологията, патогенезата и лечението на гестационния захарен диабет. Medinfo. 8, 4,23-28, (2008) ISSN 1313-2466
          44. Петкова К., К. Тодорова–Ананиева, М. Стаменова. Протеини на топлинния стрес. Мед. Преглед, 44, 1, 32-43, (2008), ISSN 1313-9134
          45. Тодорова К., К. Петкова, М Стаменова. Актуални аспекти в етиологията на захарния диабет. Български медицински журнал. (2008), ISSN 1313-1516
          46. Зашева Диана, Румен Димитров, Мария Стаменова. Ендометриоза и роля на интегрините в патогенезата на ендометриоза. Акушерство и гинекология, том 46, бр.5, 37-48, (2007), ISSN 0324-0959.
          47. Катя Тодорова, Камелия Петкова, Мария Стаменова. Протеини на топлинния шок в репродукцията. Акушерство и гинекология,8, 46, 16-22, (2007), ISSN 0324-0959
          48. Kestendjieva S, Mourdjeva M, Kyukchiev D, Mehandjiev Tz, Nickolova A, Kyurkchiev S. Isolation and characterization of umbilical vein mesenchymal stem cells. Compt. Rend. Bulg. Acad. Sci., 59, 775-780, 2006.
          49. Bochev I, Kyurkchiev D, Tivchev P, Tzvetanov L, Kyurkchiev S. Isolation and immunomodulatory activity of bone marrow mesenchymal stem cells. Compt. Rend. Bulg. Acad. Sci., 59, 775-780, 2006.
          50. Dimitrov R, Timeva T, Stameneova M, Kyurkchiev D, Shterev A, Kyurkchiev S Effect of peritoneal fluid from patients with endometriosis on morphological characterisation of endosalpinx stromal cell culture. Compt. Rend. Bulg. Acad. Sci., 59, 775-780, 2006.
          51. Hayrabedyan S., Kyurkchiev S., Kehayov I. Evaluation of IL-1α Expression in Endometriotic Lesions Using Quantitative Immunohistochemistry Approach. Compt. Rend. Bulg. Acad. Sci., 59, /2/, 229, 2006.
          52. М. Мурджева. Регулация и значение на апоптозата при стволови клетки. Pепродуктивно здраве, 11, 18-25; 2005
          53. Z. Popova, M. Mourdjeva, S. Kyurkchiev, I. Kehavyov. Internalization Of Exposed Phosphatidylserine After Treatment With Low Doses Of H2O2. Comptes rendus de l’Academie bulgare des Sciences, Vol. 58, N 11, 1319-1324, 2005.
          54. С. Кюркчиев. Стволови клетки – класификация, определения. Репрод.Здраве, 11, 3 – 10, 2005.